Coronary Artery Brachytherapy and Other Adjuncts to Coronary Interventions
Number: 0491
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses coronary artery brachytherapy and other adjuncts to coronary interventions.
-
Medical Necessity
Aetna considers the following interventions medically necessary:
- Coronary artery brachytherapy (i.e., intra-coronary radiation) in native coronary arteries or coronary artery bypass grafts as adjunctive treatment during a second angioplasty/stent placement when blockage has re-occurred within the localized area of a previously placed bare metal stent (i.e., in-stent re-stenosis);
- Abciximab (ReoPro) as an adjunctive treatment for persons undergoing percutaneous angioplasty/stent placement;
- Intravascular shockwave lithotripsy (IVL) for treatment of hemodynamically significant, heavily calcified coronary stenoses (e.g., calcium extending over 270 degrees) where primary stenting is not possible.
-
Experimental, Investigational, or Unproven
The following interventions are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:
- Coronary artery brachytherapy for use with drug-eluting stents, and for the primary prevention of re-stenosis and all other indications (except for those listed in policy section above) due to insufficient evidence in the peer-reviewed literature;
- The use of abciximab for the following indications (not an all-inclusive list) because there is currently insufficient evidence from randomized controlled trials regarding its safety or effectiveness for these indications:
- Acute ischemic stroke;
- Acute limb ischemia;
- Acute myocardial infarction without percutaneous intervention;
- Cardiac complications (e.g., coronary artery aneurysms) of Kawasaki disease;
- Saphenous vein graft interventions;
- Stenting of superficial femoral occlusive disease;
- Thromboembolic complications during cerebral aneurysm coiling;
- Thrombus resolution during intracranial bypass surgery;
-
Abciximab/heparin therapy for left ventricular assist device implantation in individuals with heparin-induced thrombocytopenia.
-
Related Policies
-
- CPB 0228 - Cardiac Computed Tomography (CT), Coronary CT Angiography, Calcium Scoring and CT Fractional Flow Reserve
- CPB 0382 - Intravascular Ultrasound
- CPB 0477 - Balloon Valvuloplasty
- CPB 0568 - Thrombectomy Systems
- CPB 0621 - Drug-Eluting Stents
- CPB 0829 - Intravascular Optical Coherence Tomography
Background
Intracoronary brachytherapy is used to prevent restenosis of an artery after angioplasty or stent placement by delivering a small amount of radiation to the treated area, which may reduce the need for additional angioplasty or bypass surgery. The radiation is intended to discourage the overgrowth of normal tissue as the healing process occurs.
When treating coronary artery disease with angioplasty or stents, the recurrence of coronary artery blockage at the site of treatment remains a significant risk. Recurrent coronary stenosis occurs in 20 to 30% of patients in whom stents have been implanted for the treatment of obstructive lesions; when it occurs within the stent, it is referred to as in-stent re-stenosis. According to generally accepted guidelines, if re-stenosis occurs within a stent, it can usually be treated by pharmacotherapy and/or repeat angioplasty followed by brachytherapy.
A special catheter is used to radiate a localized area. The catheter is passed into the coronary arteries and across the target area. Once the targeted area of stenosis is "bracketed" by the catheter, the radiation is applied.
- gamma radiation and
- beta radiation.
In its FDA submission for the Checkmate System, the Cordis Corporation cited 6-month angiographic results from 3 landmark single- and multi-center randomized clinical trials (GAMMA-I with 252 patients, WRIST with 130 patients, and SCRIPPS-I with 60 patients). Results from these trials consistently showed a significant reduction in both angiographic and clinical in-stent re-stenosis versus placebo, as well as reduced major adverse clinical events. In the GAMMA-I trial, the rate of re-stenosis was reduced by 42% by coronary artery radiation. In the patients treated with gamma radiation, 24% experienced re-stenosis, whereas in the control group not treated with radiation, 42% had re-stenosis. The device is indicated for the delivery of therapeutic doses of gamma radiation for the purpose of reducing in-stent re-stenosis. The system is for use in the treatment of native coronary arteries (2.75 to 4.0 mm in diameter and lesions up to and including 45 mm in length) with in-stent re-stenosis following percutaneous revascularization using current interventional techniques.
The FDA-approved product labeling for the Cordis Checkmate System states that the device should not be used in patients who are not good candidates for blood-thinning drugs or anti-platelet therapy.
In its FDA submission for the Novoste Beta-Cath System, the Novoste Corporation cited data from the START trial, a multi-center, randomized, placebo-controlled trial involving 476 patients. At 8 months, re-stenosis had occurred in 14% of the stented segments in patients who had received radiation, as compared with 41% of the controls. The device is indicated to deliver beta radiation to the site of successful percutaneous coronary intervention for the treatment of in-stent re-stenosis in native coronary arteries with discrete lesions (treatable with a 20 mm balloon) in a reference vessel diameter ranging from 2.7 mm to 4.0 mm.
The FDA-approved product labeling for the Beta-Cath System states that it should not be used for patients with unprotected left main coronary artery disease (50% narrowing of the coronary artery) or for patients who are not candidates for blood-thinning drugs or anti-platelet therapy.
- total radiation cohort (those receiving either angioplasty or a stent);
- those receiving angioplasty and radiation; and
- those receiving angioplasty, stent and radiation.
In those patients receiving angioplasty and radiation, the rate of in-lesion re-stenosis was significantly reduced (21.4% versus 34.3% placebo control). In the group receiving angioplasty, stent, and radiation, the radiation had a positive effect on preventing re-stenosis at the initial lesion site (21.1% versus 33.0% placebo control) but had a negative effect on the adjacent edges, leading to higher clinical re-stenosis compared with placebo (44.9% versus 35.3%).
Coronary artery brachytherapy has been shown to be effective in preventing re-stenosis in coronary artery bypass grafts. Waksman et al. (2002) reported on the results of the SVC-WRIST Trial, a randomized controlled clinical trial of the effects of intra-coronary gamma brachytherapy in 120 patients with in-stent re-stenosis of saphenous vein grafts. After 6 months, the re-stenosis rate was lower in the 60 patients assigned to gamma brachytherapy than in the 60 assigned to placebo (21% versus 44%, p = 0.005). At 12 months, the rate of re-vascularization of the target lesion was 70% lower in the gamma brachytherapy group than in the placebo group (17% versus 57%, p < 0.001), and the rate of major cardiac events was 49% lower (32% versus 63%, p < 0.001). The investigators concluded that these results support the use of brachytherapy for the treatment of in-stent re-stenosis in patients with bypass grafts.
Castagna et al. (2002) reported on the 6-month follow-up of 45 of 120 patients in the SVC-WRIST trial with restenotic lesions of saphenous vein grafts who were evaluated by intra-vascular ultrasound (IVUS). (Because the SVC-WRIST Trial protocol did not mandate IVUS, not all trial participants were evaluated with this procedure.) The investigators reported a significant reduction in repeat stenosis in the patients randomized to gamma brachytherapy compared to placebo; they noted that the effectiveness of gamma brachytherapy in patients with re-stenosis of saphenous vein grafts was similar to that reported in other trials of gamma radiation therapy in patients with re-stenosis of native coronary lesions. The investigators concluded that intra-vascular brachytherapy effectively reduced intimal hyperplasia re-accumulation in vein graft in-stent re-stenosis with no deleterious effect on reference segments within 6 months.
Oliver and colleagues (2008) performed a meta-analysis of randomized trials assessing the outcome of vascular brachytherapy (VBT) or drug-eluting stents (DES) for the treatment of coronary artery in-stent restenosis (ISR). Studies utilizing DES or VBT for ISR were identified through a systematic search. Data were pooled, and combined overall effect measures were calculated for a random effects model in terms of deaths, myocardial infarctions, re-vascularization, binary restenosis, mean late luminal loss, and major adverse cardiac events (MACE). A total of 14 eligible studies (3,103 patients) were included. Neither therapy had any effect on mortality or myocardial infarction rates. Vascular brachytherapy reduced the rate of re-vascularization (risk ratio [RR] 0.59, 95% confidence interval [CI]: 0.50 to 0.68), MACE (RR 0.58, 95% CI: 0.51 to 0.67), binary re-stenosis (RR 0.51, 95% CI: 0.44 to 0.59), and late loss (-0.73 mm, 95% CI: -0.91 to -0.55 mm) compared to balloon angioplasty and selective bare metal stents (BMS) alone at intermediate follow-up, and MACE (RR 0.72, 95% CI: 0.61 to 0.85) at long-term follow-up. Drug-eluting stents reduced the rate of re-vascularization (odds ratio [OR] 0.51, 95% CI: 0.36 to 0.71), MACE (OR 0.55, 95% CI: 0.39 to 0.79), and binary re-stenosis (OR 0.57, 95% CI: 0.40 to 0.81) compared to VBT, but follow-up was limited to 9 months. The authors concluded that VBT improves the long-term outcome of angioplasty compared with BMS alone in the treatment of ISR. Drug-eluting stents appear to provide similar results to VBT during short-term follow-up.
Beta radiation is considered investigational in the prevention of de novo lesions in patients at higher risk of re-stenosis undergoing angioplasty and/or stenting. While the initial data are promising in patients receiving angioplasty and radiation, further randomized, multi-center, placebo-controlled trials are needed to investigate the long-term effects of radiation and the risk of edge re-stenosis in the primary prevention of re-stenosis.
Many questions concerning the safety (e.g., late thrombosis, re-stenosis at the proximal and distal edges of irradiated zones, myocardial infarction) of radiation for in-stented re-stenosis have been raised in the literature. Some authorities believe that, until these questions can be answered by additional randomized, well-controlled clinical trials with larger numbers of patients, in different populations, and with long-term follow-up, physicians should remain cautious in their use of this technique.
Anti-Platelet Therapy
Intravenous platelet glycoprotein IIb/IIIa receptor inhibitors have been demonstrated to reduce the incidence of ischemic complications when used in conjunction with coronary interventions. ReoPro (abciximab) is a monoclonal antibody that forms a complex with glycoprotein IIb/IIIa receptors at the surface of blood platelets. Because ReoPro blocks these receptors it prevents the platelets from adhering to each other and from forming blood clots. According to the FDA-approved product labeling, ReoPro is indicated as an adjunct to percutaneous coronary interventions for the prevention of cardiac ischemic complications:
- In patients undergoing percutaneous coronary intervention;
- In patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours.
Use of abciximab in patients not undergoing percutaneous coronary intervention has not been studied. Abciximab is intended for use with aspirin and heparin and has been studied only in that setting.
Stent implantation in the superficial femoral artery has been associated with suboptimal results, while glycoprotein IIb/IIIa inhibitors have shown improved procedural outcomes during coronary intervention. In a randomized, placebo-controlled trial, Ansel et al. (2006) assessed the effect of abciximab during nitinol stenting of superficial femoral occlusive disease. Major outcome measures included 9-month re-stenosis, defined as a decrease in ankle-brachial index and in-stent duplex ultrasound restenosis, and adverse events defined as death (30 days) or repeat re-vascularization within 9 months. A total of 27 patients were randomized to receive abciximab and 24 patients to control (placebo). The primary endpoint of cumulative re-stenosis occurred in 15.4% of patients given abciximab and in 12% administered placebo (p = 0.873). The primary re-stenosis endpoint in diabetics and total occlusions were similar at 14.3% and 15.4%, respectively. The composite endpoint of 30-day mortality and 9-month re-vascularization occurred in 5.8% of the abciximab group and 0% of the placebo group (p = 0.274), with no 30-day deaths reported. Graded treadmill time and Rutherford class were significantly improved in both groups, but the abciximab group did not demonstrate any identifiable effect. The authors concluded that nitinol stenting of the superficial femoral artery was associated with favorable functional outcomes at 9 months, but adjunctive abciximab did not appear to demonstrate any identifiable effect.
In a Cochrane review on glycoprotein IIb/IIIa inhibitors for acute ischemic stroke (Ciccone et al., 2006), the authors concluded that there is currently insufficient evidence from randomized controlled trials regarding the safety or effectiveness of glycoprotein IIb/IIIa inhibitor therapy in the management of patients with acute ischemic stroke.
Seitz and Siebler (2008) reviewed the literature concerning the use of intravenously administered glycoprotein IIb/IIIa inhibitors (GPIs) abciximab, eptifibatide, and tirofiban for the treatment of patients with acute ischemic brain infarction. In multi-center, prospective, randomized, and placebo-controlled trials, abciximab had a higher risk of cerebral bleeding, while tirofiban did not increase hemorrhage. When combined with fibrinolysis, abciximab and tirofiban were found to improve cerebral artery re-canalization and tissue re-perfusion, resulting in reduced infarct volumes and improved neurological outcomes. Thus, GPIIb/IIIa-receptor antagonists have great potential for the treatment of acute stroke.
In a phase-III clinical trial, Adams and colleagues (2008) examined the relative safety and effectiveness of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours of symptom onset. The planned enrollment was 1,800 patients. The primary cohort enrolled patients who could be treated within 5 hours of stroke onset, while a companion cohort enrolled participants treated 5 to 6 hours after stroke, as well as a smaller cohort of patients treated within 3 hours of stroke onset upon awakening. The primary outcome measure was the dichotomous modified Rankin Scale score at 3 months, adjusted for the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intra-cranial hemorrhage that occurred within 5 days of stroke. The trial was terminated prematurely after 808 patients in all cohorts were enrolled, based on the recommendation of an independent safety and effectiveness monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned to placebo (72/218) and 32% of patients assigned to abciximab (71/221; p = 0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, approximately 5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intra-cranial hemorrhage (p = 0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo). The authors concluded that this trial did not demonstrate either safety or effectiveness of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke, regardless of endpoint or population studied. There was an increased rate of symptomatic or fatal intra-cranial hemorrhage in the primary and wake-up cohorts.
Schulz et al. (2010) noted that in the Bavarian Reperfusion Alternatives Evaluation (BRAVE)-3 study, upstream administration of abciximab in addition to 600 mg clopidogrel loading did not reduce infarct size in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PCI). The aim of this study was to investigate 1-year clinical outcomes in the BRAVE-3 study patients. A total of 800 patients with acute STEMI within 24 hours from symptom onset, all treated with 600 mg of clopidogrel, were randomized in a double-blind fashion to receive either abciximab (n = 401) or placebo (n = 399) in the intensive care unit before being sent to the catheterization laboratory. The main outcome of interest in the present study, the composite of death, recurrent myocardial infarction, stroke, or re-vascularization of the infarct-related artery (IRA) at 1 year, was 23.0% (92 patients) in the abciximab group versus 25.7% (102 patients) in the placebo group [RR = 0.90, 95% CI: 0.67 to 1.20; p = 0.46]. The combined incidence of death, recurrent myocardial infarction, or stroke was 9.3% in the abciximab group versus 6.0% in the placebo group (RR = 1.55, 95% CI: 0.93 to 2.58; p = 0.09). There was a significant reduction in IRA re-vascularization with abciximab compared to placebo (16.3% versus 22.3%; RR = 0.71, 95% CI: 0.52 to 0.98; p = 0.04). The authors concluded that in patients with STEMI, all receiving 600 mg clopidogrel, abciximab did not improve overall clinical outcomes at 1 year after PCI.
Dong et al. (2010) performed a meta-analysis to evaluate the relative safety and efficacy of upstream versus deferred administration of small-molecule GPIs (smGPIs) in STEMI patients. A total of 10 randomized clinical trials comparing upstream versus deferred administration of smGPIs in 2,724 patients were located in the electronic databases of the published literature. Pre-procedural Thrombolysis In Myocardial Infarction Study (TIMI) grade 2 or 3 flow was present in 45.0% of the upstream group compared with 36.9% in the deferred group (OR 1.40, p < 0.001). However, no difference in post-procedural TIMI 3 flow (OR 0.87, p = 0.25) was found between the groups. The 30-day mortality rate in the upstream group did not differ from that of the deferred group (OR 1.04, p = 0.85). No significant difference was noted with respect to major bleeding complications (OR 1.25, p = 0.38). The authors concluded that in STEMI patients scheduled for primary PCI, although early smGPI treatment improved initial epicardial patency, no beneficial effect on post-procedural angiographic or 30-day clinical outcomes was found. Thus, the current available data do not support the routine utilization of upstream smGPIs in STEMI patients treated with primary PCI.
Thiele and colleagues (2012) examined the safety and effectiveness of intra-coronary (IC) versus standard intravenous (IV) bolus application in patients with ST-elevation myocardial infarction (STEMI) undergoing this intervention. The AIDA STEMI trial was a randomized, open-label, multi-center trial. Patients presenting with STEMI within the previous 12 hours and with no contraindications for abciximab were randomly assigned in a 1:1 ratio by a central web-based randomization system to receive IC versus IV abciximab bolus (0.25 mg/kg body weight) during PCI, with a subsequent 12-hour IV infusion of 0.125 μg/kg/min (maximum 10 μg/min). The primary endpoint was a composite of all-cause mortality, recurrent infarction, or new congestive heart failure within 90 days of randomization. Secondary endpoints included the time to occurrence of the primary endpoint, each individual component of that endpoint, early ST-segment resolution, TIMI flow grade, and enzymatic infarct size. A masked central committee adjudicated the primary outcome and its components. Treatment allocation was not concealed from patients and investigators. Between July 2008 and April 2011, a total of 2,065 patients were randomly assigned to IC abciximab (n = 1,032) or IV abciximab (n = 1,033). Intra-coronary abciximab, as compared with IV abciximab, resulted in a similar rate of the primary composite clinical endpoint at 90 days in 1,876 analyzable patients (7.0% versus 7.6%; OR 0.91; 95% CI: 0.64 to 1.28; p = 0.58). The incidence of death (4.5% versus 3.6%; 1.24; 0.78 to 1.97; p = 0.36) and re-infarction (1.8% versus 1.8%; 1.0; 0.51 to 1.96; p = 0.99) did not differ between the treatment groups, whereas fewer patients in the IC group had new congestive heart failure (2.4% versus 4.1%; 0.57; 0.33 to 0.97; p = 0.04). None of the secondary endpoints or safety measures differed significantly between groups. The authors concluded that in patients with STEMI undergoing primary PCI, IC abciximab did not result in a difference in the combined endpoint of death, re-infarction, or congestive heart failure compared to IV abciximab. Since IC abciximab bolus administration is safe and might be related to reduced rates of congestive heart failure, the IC route might be preferred if abciximab is indicated in high-risk patients.
Stone and colleagues (2012) examined whether bolus IC abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. Between November 28, 2009, and December 2, 2011, a total of 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion underwent primary PCI with bivalirudin anti-coagulation and were randomized in an open-label, 2:2 factorial design to bolus IC abciximab delivered locally at the infarct lesion site versus no abciximab, and to manual aspiration thrombectomy versus no thrombectomy. A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6-F aspiration catheter. The primary endpoint was infarct size (percentage of total left ventricular mass) at 30 days, assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab versus no abciximab groups (pooled across the aspiration randomization); the major secondary endpoint was 30-day infarct size in the aspiration versus no aspiration groups (pooled across the abciximab randomization). Evaluable cMRI results at 30 days were available for 181 and 172 patients randomized to IC abciximab versus no abciximab, respectively, and for 174 and 179 patients randomized to manual aspiration versus no aspiration, respectively. Patients randomized to IC abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range (IQR), 6.8% to 22.7%; n = 181, versus 17.9% (IQR, 10.3% to 25.4%); n = 172; p = 0.03). Patients randomized to IC abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g (IQR, 7.4 to 31.3 g); n = 184, versus 24.0 g (IQR, 12.1 to 34.2 g); n = 175; p = 0.03), but not in abnormal wall motion score (median, 7.0 (IQR, 2.0 to 10.0); n = 188, versus 8.0 (IQR, 3.0 to 10.0); n = 184; p = 0.08). Patients randomized to aspiration thrombectomy versus no aspiration had no significant difference in infarct size at 30 days (median, 17.0% (IQR, 9.0% to 22.8%); n = 174, versus 17.3% (IQR, 7.1% to 25.5%); n = 179; p = 0.51), absolute infarct mass (median, 20.3 g (IQR, 9.7 to 31.7 g); n = 178, versus 21.0 g (IQR, 9.1 to 34.1 g); n = 181; p = 0.36), or abnormal wall motion score (median, 7.5 (IQR, 2.0 to 10.0); n = 186, versus 7.5 (IQR, 2.0 to 10.0); n = 186; p = 0.89). The authors concluded that in patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin anti-coagulation, infarct size at 30 days was significantly reduced by bolus IC abciximab delivered to the infarct lesion site, but not by manual aspiration thrombectomy. Moreover, the authors stated that larger trials are needed to examine whether the degree of infarct size reduction at 30 days achieved with intra-coronary abciximab in the present study translates into improved late clinical outcomes without increasing bleeding.
De Luca et al. (2012) performed a meta-analysis of randomized controlled trials (RCTs) to assess the safety and effectiveness of IC versus IV abciximab administration in STEMI patients undergoing primary angioplasty. These researchers obtained results from all RCTs enrolling STEMI patients undergoing primary PCI. The primary endpoint was mortality, while recurrent myocardial infarction, post-procedural epicardial (TIMI 3) and myocardial (MBG 2-3) perfusion were identified as secondary endpoints. The safety endpoint was the risk of major bleeding complications. A total of 8 RCTs were finally included in the meta-analysis, enrolling a total of 3,259 patients. Compared to the IV route, IC abciximab was associated with a significant improvement in myocardial perfusion (OR (95% CI) = 1.76 (1.28 to 2.42), p < 0.001), without significant benefits in terms of mortality (OR (95% CI) = 0.85 (0.59 to 1.23), p = 0.39), re-infarction (OR (95% CI) = 0.79 (0.46 to 1.33), p = 0.37), or major bleeding complications (OR (95% CI) = 1.19 (0.76 to 1.87), p = 0.44). However, these investigators observed a significant relationship between the patient's risk profile and mortality benefits from IC abciximab administration (p = 0.011). The authors concluded that the present updated meta-analysis showed that IC administration of abciximab is associated with significant benefits in myocardial perfusion, but not in clinical outcomes at short-term follow-up compared to IV abciximab administration, without any excess of major bleeding in STEMI patients undergoing primary PCI. However, a significant relationship was observed between the patient's risk profile and mortality benefits from IC abciximab administration. Therefore, while waiting for long-term follow-up results and additional randomized trials, IC abciximab administration cannot be routinely recommended but may be considered in high-risk patients.
Eitel et al. (2013) noted that the aim of the AIDA STEMI (Abciximab IV versus IC in ST-elevation Myocardial Infarction) cardiac magnetic resonance (CMR) substudy was to investigate potential benefits of IC versus IV abciximab bolus administration on infarct size and reperfusion injury in ST-segment elevation myocardial infarction. The AIDA STEMI trial randomized 2,065 patients to IC or IV abciximab and found similar rates of major adverse cardiac events at 90 days, with significantly less congestive heart failure in the IC abciximab group. Cardiac magnetic resonance can directly visualize myocardial damage and reperfusion injury, thereby providing mechanistic and pathophysiological insights. These investigators enrolled 795 patients in the AIDA STEMI CMR substudy; CMR was completed within 1 week after ST-segment elevation myocardial infarction. Central core laboratory-masked analyses for quantified ventricular function, volumes, infarct size, microvascular obstruction, hemorrhage, and myocardial salvage were performed. The area at risk (p = 0.97) and final infarct size (16% [interquartile range: 9% to 25%] versus 17% [interquartile range: 8% to 25%], p = 0.52) did not differ significantly between the IC and IV abciximab groups. Consequently, the myocardial salvage index was similar (52 [interquartile range: 35 to 69] versus 50 [interquartile range: 29 to 69], p = 0.25). There were also no differences in microvascular obstruction (p = 0.19), intra-myocardial hemorrhage (p = 0.19), or ejection fraction (p = 0.95) between both treatment groups. Patients in whom major adverse cardiac events occurred had significantly larger infarcts, less myocardial salvage, and more pronounced ventricular dysfunction. The authors concluded that this largest multi-center CMR study in ST-segment elevation myocardial infarction patients to date demonstrated no benefit of IC versus IV abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events.
In a meta-analysis, Wang et al. (2013) stated that abciximab is a widely used adjunctive therapy for acute coronary syndrome (ACS). However, the effect of IC administration of abciximab on cardiovascular events remains unclear when compared with IV therapy. These investigators systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases and reference lists of articles and proceedings of major meetings to obtain relevant literature. All eligible trials included ACS patients who received either IC administration of abciximab or IV therapy. The primary outcome was major cardiovascular events, and secondary outcomes included total mortality, re-infarction, and any possible adverse events. Of 660 identified studies, these researchers included 9 trials reporting data on 3,916 ACS patients. Overall, IC administration of abciximab resulted in a 45% reduction in relative risk for major cardiovascular events (RR; 95% CI: 24 to 60%), a 41% reduction in RR for re-infarction (95% CI: 7 to 63%), and a 44% reduction in RR for congestive heart failure relative to IV therapy (95% CI: 8 to 66%); however, compared to IV therapy, IC administration of abciximab had no effect on total mortality (RR, 0.69; 95% CI: 0.45 to 1.07). No other significant differences were identified between the effects of IC abciximab administration and IV therapy. The authors concluded that IC administration of abciximab can reduce the risk of major cardiovascular events, re-infarction, and congestive heart failure when compared with IV therapy.
Intravascular Shockwave Lithotripsy for the Treatment of Coronary Artery Plaques
Intravascular lithotripsy (IVL) is an emerging endovascular technology used during percutaneous coronary intervention (PCI) to treat heavily calcified coronary lesions by delivering pulsatile acoustic shock waves from a specialized balloon catheter to fracture superficial and deep calcium, thereby improving vessel compliance and enabling optimal stent expansion. This technique operates at low balloon pressures (4–6 atm) and aims to provide a safer alternative to atherectomy by reducing risks such as perforation, abrupt closure, and slow flow, while maintaining procedural simplicity due to its familiar balloon-based platform.
In February 2021, the FDA approved the Shockwave Intravascular Lithotripsy (IVL) System with the Shockwave C2 coronary IVL catheter, which is indicated for lithotripsy-enabled, low-pressure balloon dilatation of severely calcified, stenotic de-novo coronary arteries before stenting. However, there is currently insufficient evidence to support the effectiveness of IVL for this indication.
Kereiakes et al. (2020) stated that coronary calcification limits optimal stent expansion and apposition, worsening safety and effectiveness outcomes of percutaneous coronary intervention (PCI). Current ablative technologies that modify calcium to optimize stent deployment are limited by guide-wire bias and peri-procedural complications related to athero-embolization, coronary dissection, and perforation. Intravascular lithotripsy delivers pulsatile ultrasonic pressure waves via a fluid-filled balloon into the vessel wall to modify calcium and enhance vessel compliance, reduce fibro-elastic recoil, and decrease the need for high-pressure balloon (barotrauma) inflations. IVL has been used in peripheral arteries as stand-alone revascularization or as an adjunct to optimize stent deployment. The Disrupt CAD III is a prospective, multi-center, single-arm study designed to examine the safety and effectiveness of the Shockwave coronary IVL catheter to optimize coronary stent deployment in patients with de novo calcified coronary stenoses. The primary safety endpoint was freedom from MACE (composite of cardiac death, MI, and target vessel revascularization [TVR]) at 30 days compared to a pre-specified performance goal. The primary effectiveness endpoint was procedural success without in-hospital MACE. Enrollment for this trial will complete early in 2020, with clinical follow-up ongoing for 2 years. The authors stated that the Disrupt CAD III will examine the safety and effectiveness of the Shockwave coronary IVL catheter to optimize coronary stent deployment in patients with calcified coronary stenoses.
Hill et al. (2020) noted that coronary calcification hinders stent delivery and expansion and is associated with adverse outcomes. Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhancing vessel compliance and optimizing stent deployment. In a prospective, single-arm, multi-center study, these researchers examined the safety and effectiveness of IVL in severely calcified de novo coronary lesions. This trial (Disrupt CAD III) was designed for regulatory approval of coronary IVL. The primary safety endpoint was freedom from MACE (cardiac death, MI, or target vessel revascularization) at 30 days. The primary effectiveness endpoint was procedural success. Both endpoints were compared with a pre-specified performance goal (PG). The mechanism of calcium modification was assessed in an optical coherence tomography (OCT) sub-study. A total of 431 patients were enrolled at 47 sites in 4 countries. The primary safety endpoint of the 30-day freedom from MACE was 92.2%; the lower bound of the 95% CI was 89.9%, which exceeded the PG of 84.4% (p < 0.0001). The primary effectiveness endpoint of procedural success was 92.4%; the lower bound of the 95% CI was 90.2%, which exceeded the PG of 83.4% (p < 0.0001). Mean calcified segment length was 47.9 ± 18.8 mm, calcium angle was 292.5 ± 76.5°, and calcium thickness was 0.96 ± 0.25 mm at the site of maximum calcification. OCT demonstrated multi-plane and longitudinal calcium fractures after IVL in 67.4% of lesions. Minimum stent area was 6.5 ± 2.1 mm² and was similar regardless of demonstrable fractures on OCT. The authors concluded that coronary IVL safely and effectively facilitated stent implantation in severely calcified lesions. Moreover, these researchers stated that longer-term clinical follow-up (ongoing in this study through 2 years) is needed to determine the durability of clinical benefit associated with IVL-optimized stent implantation. They stated that future studies should include more complex patient and angiographic lesion subsets to examine the generalizability of these observations and clarify the relationships between measures of calcium fracture, stent expansion, and long-term clinical outcomes.
The authors stated that this study had several drawbacks. First, the non-randomized study design lacked a concurrent control group. The comparison to an objective PG is an established pathway for investigational device exemption (IDE) approval and was derived in conjunction with the FDA. Orbital atherectomy was similarly approved in the U.S. based on a single-arm study that used an objective PG design. The high absolute procedural success rate and low absolute peri-procedural MACE rate (despite the severity of lesion calcification in the study population), coupled with its ease of use and rapid learning curve, suggested that IVL may play an important role in the treatment of complex, high-risk calcified lesions. Second, the endpoint definitions for both peri-procedural MI and procedural success were chosen to match those used in the ORBIT II study for regulatory purposes and did not reflect current standards. Nevertheless, pre-specified sensitivity analyses using more contemporary definitions support and confirm the conclusions derived from the primary endpoint analyses. Third, OCT identified calcium fractures in 67.4% of lesions after IVL; however, excellent minimum stent area (MSA), area stenosis, and stent expansion outcomes were observed regardless of calcium fracture visualization. This may represent a limitation of OCT to detect subtle morphological changes in calcified plaque that are beyond the resolution limits of current OCT technology. Fourth, protocol exclusion of adjunctive tools for plaque modification (atherectomy or cutting/scoring balloons) to facilitate IVL balloon crossing avoided confounding of the efficacy and the known complications associated with these devices and afforded an objective assessment of the mechanism of IVL plaque modification. Finally, although protocol exclusion of extremely tortuous vessels, true bifurcation lesions, and unprotected left main or ostial target lesions precluded generalizability of study findings to these subgroups, affording a cross-study comparison with the ORBIT II trial required enrollment of a similar study population. Future studies are needed to examine if there are any specific clinical or anatomic circumstances that are particularly suited to and are more safely or effectively treated with one or the other of these alternative lesion preparation strategies. Preliminary clinical experience suggested that atheroablative technologies may be required in specific situations to facilitate IVL balloon placement and that these techniques may be complementary.
Oksnes et al. (2021) noted that IVL has been shown to be safe and effective for calcium modification in nonocclusive coronary artery disease (CAD); however, there were only case reports of its use in calcified chronic total occlusions (CTO). In a retrospective, observational, cohort study, these investigators reported data from an international multi-center registry of IVL use during CTO-PCI and provided provisional data regarding its safety and effectiveness. During the study period, IVL was used in 55 of 1,053 (5.2%) CTO-PCI procedures. IVL was used within the occluded segment after successful CTO crossing in 53 procedures and during incomplete CTO crossing in 2 cases. The mean Japanese-CTO (J-CTO) score was 3.1. CTO-PCI technical and procedural success was achieved in 53 (96%) and 51 (93%) cases, respectively; 6 patients had a procedural complication, with 3 main vessel perforations (5%); 2 had covered stent implantation, 1 required pericardiocentesis, and 1 was managed conservatively. All had combination therapy with another calcium modification device; 2 patients had a procedural MI (PMI) (4%), and 2 others had a MACE (4%) at a median follow-up of 13 (4 to 21) months. The authors concluded that IVL can effectively facilitate calcium modification during CTO-PCI. Moreover, these researchers stated that further investigation is needed to establish the safety and effectiveness of IVL and other calcium modification devices when used extra-plaque or in combination during CTO-PCI.
The authors stated that the main drawback of this study was that it was a retrospective, observational cohort study. Furthermore, it should be noted that IVL was used after CTO crossing in almost all cases, thus introducing bias to procedural success rates. A period of novel technology adoption and the impact of incremental device cost will have introduced some case selection bias, increasing the proportion of cases where an additional calcium modification device was used before IVL, where with improved access and more experience, IVL could be the first-choice device when initial treatment with non-compliant balloon dilation or scoring/cutting balloon, or rotational atherectomy has failed. While IVL was used in 90% of the procedures, quantitative data was not available for analysis.
Aksoy et al. (2021) stated that data regarding the safety, effectiveness, and outcome of IVL in comparison to standard techniques are lacking. In a retrospective, single-center study, these researchers compared IVL with non-compliant high-pressure balloon percutaneous coronary angioplasty (PTCA). They carried out a retrospective, propensity-score-matched study to compare procedural success in 57 consecutive patients who received IVL-guided PCI in calcified coronary lesions (CCAD) with 171 matched patients who were treated with high-pressure PTCA with a non-compliant (NC) balloon. The mean minimal lumen diameter (MLD) for the IVL group was 1.08 ± 0.51 mm, and the median percent diameter stenosis on quantitative angiography was 70.2% (IQR, 60.2% to 78.6%). MLD in the high-pressure dilatation group was 0.97 ± 0.43 mm, and the median percent diameter stenosis was 71.5% (IQR, 58.5% to 77.0%). IVL-guided PCI reduced median stenosis to 17.5% (IQR, 9.3% to 19.8%) with an acute gain of 0.93 ± 0.7 mm. High-pressure dilatation resulted in a final median stenosis of 19.3% (IQR, 13.33% to 28.5%). Procedural success was significantly higher (82.5% versus 61.4%; p: 0.0035) in the IVL group. MACE through 12 months occurred in 10.5% of cases in the IVL group and in 11.1% of the high-pressure group (p = 0.22). Angiographic complications (coronary dissection, slow or no reflow, new coronary thrombus formation, abrupt vessel closure) were very low (0.2% versus 0.12%). The authors concluded that IVL resulted in a significantly higher rate of procedural success compared to high-pressure NC-balloon dilatation in patients with CCAD. The rate of MACE through 12 months was similar to the standard therapy.
The authors stated that this study had several drawbacks. First, this was a retrospective, single-center study; a randomized study comparing IVL against conventional non-compliant balloon dilation or scoring/cutting balloon strategies would improve the knowledge of the safety and effectiveness of the technique. Second, patient inclusion into the study was based on the angiographic degree of calcification and not on intravascular imaging. Optical coherence tomography (OCT)/IVUS were performed in approximately 25% of cases. This represented well the clinical routine in an all-comers cohort; however, for analyses of patients with an unsuccessful procedure (those with residual in-stent stenosis of greater than 20%), pre-procedural intravascular imaging would have improved the failure analysis. Third, IVL may have limitations in asymmetrical calcifications. These clinical situations, as well as cost analyses, have not yet been performed.
In a retrospective, observational, single-arm study, Umapathy et al. (2021) examined the clinical and angiographic outcomes of coronary IVL use in an all-comers population with moderate-to-severe CCAD. The primary endpoint was in-hospital MACE, which included cardiac death, MI, and TVR; and secondary endpoints were clinical success (stent expansion with less than 30% in-stent residual stenosis and no in-hospital MACE) and angiographic success. Between August 2019 and December 2019, a total of 50 calcified lesions were treated in 45 patients using the Shockwave C2 IVL catheter. They were further studied in 3 treatment subgroups: primary IVL group with de novo lesions (n = 23 lesions); secondary IVL group in which non-compliant balloon dilation failed (n = 15 lesions); and tertiary IVL group with IVL to under-expanded stents (n = 12 lesions). The mean diameter stenosis of calcified lesions was 63.2 ± 10.2% at baseline and decreased to 33.5 ± 10.9% immediately following IVL (p < 0.001) and 15 ± 7.1% following stenting (p < 0.001). Mean MLD was 1.1 ± 0.3 mm at baseline and increased to 1.90 ± 0.5 mm following IVL (p < 0.001) and 2.80 ± 0.50 mm following stenting (p < 0.001). In-hospital and 30-day MACE occurred in 3 and 4 patients, respectively. Overall, clinical success and angiographic success were achieved in 90% and 94% of cases, respectively. The authors concluded that IVL appeared to be a safe, effective, and feasible strategy for calcium modification in an all-comers cohort with a high success rate, minimal procedural complications, and low MACE rates. Moreover, these researchers stated that larger randomized studies of IVL with long-term follow-up are needed to confirm these initial findings.
The authors stated that the drawbacks of this study included that this was a retrospective, single-arm registry with short-term follow-up to 30 days. The small study cohort of 50 IVL-treated lesions had fewer patients in each treatment subgroup; therefore, results of the subgroup analyses should be considered exploratory and hypothesis-generating.
Liang and Gu (2021) stated that previous understanding holds that rotational atherectomy and modified balloons remain the default strategy for severely calcified coronary stenoses. In recent years, coronary IVL provides new ideas. These researchers examined the safety and effectiveness of IVL for the treatment of severely calcified coronary stenoses. The serial Disrupt CAD trials (Disrupt CAD I, Disrupt CAD II, Disrupt CAD III, and Disrupt CAD IV) were included in this study. The safety endpoint was freedom from MACE in hospital, at 30 days, and at 6 months following the index procedure. The effectiveness endpoints included procedural success and angiographic success. OCT was used to evaluate the mechanism of action of IVL, quantifying the coronary artery calcification (CAC) characteristics and calcium plaque fracture. These investigators enrolled a total of 628 patients with a mean age of 71.8 years, 77.1% men. In these patients, the left anterior descending artery and right coronary artery were the most vulnerable vessels. The diameter stenosis was 64.6 ± 11.6% and the lesion length was 24.2 ± 11.4 mm. IVL had a favorable efficacy (93.0% procedural success, 97.5% angiographic success, and 100.0% stent delivery). Among the 628 patients, 568, 568, and 60 reported MACE endpoints in hospital, at 30 days, and at 6 months, respectively. The results showed that 528, 514, and 55 patients were free from MACE in hospital, at 30 days, and at 6 months, respectively; and OCT measurements demonstrated that calcium fracture was the underlying mechanism of action for coronary IVL. The authors concluded that IVL is an efficient vessel preparation strategy in the presence of a heavy coronary calcium burden, and these findings appeared to be consistent regardless of ethnicity or geography. Moreover, calcium fracture facilitated increased vessel compliance and favorable stent expansion. Furthermore, the impact of this technology on the long-term prognosis of patients with severe calcification is also the focus of attention and expectation. More importantly, the advantage of IVL over the other methods in this particular population is still unknown. Enhancing the comparison of IVL would aid in guiding the therapeutic decisions in these patients. These researchers hope that one day this technology can eventually replace the other coronary calcification treatment technologies currently used in clinical practice.
Kereiakes et al. (2021) examined the cumulative safety and effectiveness of coronary intravascular lithotripsy (IVL). Patient data were pooled from the Disrupt CAD studies, which shared uniform study criteria, endpoint definitions and adjudication, and procedural follow-up. The primary safety endpoint was freedom from major adverse cardiovascular events (MACE, composite of cardiac death, all MI, or TVR) at 30 days. The primary effectiveness endpoint was procedural success, defined as stent delivery with a residual stenosis of 30% or less by quantitative coronary angiography without in-hospital MACE. Secondary outcomes included serious angiographic complications, target lesion failure, cardiac death, and stent thrombosis at 30 days. Between December 2015 and April 2020, a total of 628 patients were enrolled at 72 sites from 12 countries. The presence of severe calcification was confirmed in 97.0% of target lesions, with an average calcified segment length of 41.5 ± 20.0 mm. The primary safety and effectiveness endpoints were achieved in 92.7% and 92.4% of patients, respectively. At 30 days, the rates of target lesion failure, cardiac death, and stent thrombosis were 7.2%, 0.5%, and 0.8%. Rates of post-IVL and final serious angiographic complications were 2.1% and 0.3%, with no IVL-associated perforations, abrupt closure, or episodes of no reflow. The authors concluded that in the largest cohort of patients treated with coronary IVL assessed to date, coronary IVL safely facilitated successful stent implantation in severely calcified coronary lesions with a high rate of procedural success. Moreover, these researchers stated that ongoing clinical follow-up in the Disrupt CAD studies will determine whether the early results of IVL to facilitate stent implantation in severely calcified lesions would translate into high rates of long-term event-free survival.
The authors stated that this study had several drawbacks. First, although all 4 Disrupt CAD studies were carefully carried out with independent core laboratory and clinical events committee adjudication, they were all single-arm studies lacking a concurrent control population. The lack of a randomized comparator precludes definitive comparisons with balloon-based (scoring, cutting, non-compliant) or athero-ablative (rotational atherectomy [RA] or orbital atherectomy [OA], laser) techniques for PCI of severely calcified vessels. Second, sub-study data from intravascular imaging by OCT that provided insights into the proposed IVL mechanism of action were not provided in the present clinical report. Pooled analysis of this experience is ongoing and will be the focus of a future report. Nevertheless, adequate intravascular imaging data have been reported from the individual trials to support the premise of in-situ circumferential and longitudinal multi-plane calcium fracture with fracture expansion following stent implantation as the dominant mechanism of vascular calcium modification by IVL. These reports have documented high values for post-procedure percentage stent expansion and minimal stent area measured by OCT, which may favorably affect long-term TLF rates. Third, the safety and effectiveness of IVL shown in this analysis were applicable to the patient cohort studied and may not be generalizable to “all comers” with severe coronary calcification and did not apply to the routine treatment of moderately calcified lesions. Indeed, specific clinical (acute coronary syndromes) and angiographic target lesion subsets (ostial, left main, non-dilatable lesions, bypass graft, in-stent re-stenosis, lesion length of greater than 40 mm, etc.) were not included in this analysis. In addition, as the combined use of IVL with athero-ablative technologies was excluded from the Disrupt CAD studies, further investigation is needed to understand the potential complementary utility of these technologies. Data from the “real world” experience will be acquired with the forthcoming U.S. post-market study to address these study drawbacks.
Jattari et al. (2022) noted that severe coronary artery calcification (CAC) can be an arduous obstacle in interventional cardiology, often leading to suboptimal results of PCI. Coronary IVL is a novel technique that modulates severe CAC, thus facilitating stent implantation. In an observational, multi-center study, these researchers examined the feasibility, safety, and effectiveness of coronary IVL in the treatment of severe CAC. Data from 134 IVL procedures in 5 Belgian hospitals were prospectively obtained. Successful delivery of the IVL catheter was achieved in all cases but 1 (99.3%). The primary endpoint was final overall procedural success, which was obtained in 88.1% of cases, an aggregate of 92.6% in de novo lesions and 77.5% in stent under-expansion ISR. IVL therapy effect was considered successful by the operators in 94% of cases, with 68.7% achieving optimal and 25.3% achieving suboptimal results. The 1-month MACE rate was 3%, including 2 cardiovascular deaths (1 in-stent thrombosis and 1 coronary artery perforation). The authors concluded that this real-world experience suggested that shockwave IVL is a feasible, safe, and effective technique for the treatment of heavily calcified coronary lesions. Moreover, these researchers stated that further prospective and randomized studies are needed to confirm the added value when used upfront or after failure of the initially applied conventional techniques.
The authors stated that this study had several drawbacks. This was a real-life registry, including only a few procedures with intracoronary imaging due to a lack of reimbursement in Belgium. Consequently, many parameters were evaluated angiographically, including severity of calcification and the assessment of the results (suboptimal versus optimal). Similar to all studies published thus far on IVL, the main limitations were that this study was not randomized and that no long-term follow-up could be provided. Furthermore, no analysis was carried out for peri-procedural troponin rise/MI or acute cardiac injury.
Sattar et al. (2022) noted that IVL can be used to aid deploying stents in severe CAC. In a meta-analysis, studies employing IVL for CAC lesions were included. The primary outcomes included clinical and angiographic success. The secondary outcomes, including lumen gain, maximum calcium thickness, and calcium angle at the final angiography site, minimal lumen area (MLA) site, and MSA site, were analyzed by the random-effects model to calculate the pooled standardized mean difference (SMD); tertiary outcomes included safety event ratios. A total of 7 studies (760 patients) were included. The primary outcomes: pooled clinical and angiographic success event ratio percentage of IVL was 94.4% and 94.8%, respectively. On a random effect model for standard inverse variance for secondary outcomes showed: minimal lumen diameter increase with IVL was 4.68 mm (p < 0.0001, 95% CI: 1.69 to 5.32); diameter decrease in the stenotic area after IVL session was -5.23 mm (95% CI: -22.6 to 12.8). At the MLA and final MSA sites, MLA gain was 1.42 mm² (95% CI: 1.06 to 1.63; p < 0.00001) and 1.34 mm² (95% CI: 0.71 to 1.43; p < 0.00001), respectively. IVL reduced calcium thickness at the MLA site (SMD -0.22; 95% CI: -0.40 to 0.04; p = 0.02); calcium angle was not affected at the MLA site. The tertiary outcomes: the most common complication was MACEs (n = 48/669), and the least common complication was abrupt closure of the vessel (n = 1/669). The authors concluded that available evidence suggested that IVL safely and effectively facilitated stent deployment with high angiographic and clinical success rates in treating severely CCAD.
The authors stated that this meta-analysis had several drawbacks. Due to limited data, only single-arm observational studies were included; more studies, including randomized, double-blind studies, should be performed to study the safety and effectiveness in a head-to-head comparison with other calcium debulking procedures. Severe calcification definition was not uniform in included studies given the lack of consistency of imaging use, including intravascular ultrasounds and optical coherence tomography. The result of diameter stenosis had high heterogeneity, which could not be excluded given only 2 studies reported data. Furthermore, none of the included studies afforded adjunctive treatment with atherectomy or specialty cutting balloons. The post-procedural outcomes obtained therefore did not account for any form of adjunctive treatment. This study predominantly discussed the angiographic comparison of lesion outcomes pre- and post-IVL. As such, the studies included did not allow adjunctive treatment with atherectomy or specialty cutting balloons. Currently, there is no head-to-head RCT comparing atherectomy (orbital or rotational) or cutting balloons with IVL.
Mhanna et al. (2022) noted that IVL is a recently introduced therapeutic modality in the management of CCAD. These investigators carried out a comprehensive literature search for studies that examined the use of adjunctive IVL. The primary outcomes of this study were clinical success, defined as the ability of IVL to produce residual diameter stenosis of less than 50% (RDS < 50%) after stenting with no evidence of in-hospital MACEs, and angiographic success, defined as success in facilitating stent delivery with RDS < 50% and without serious angiographic complications. The secondary outcomes included post-IVL and post-stenting changes in lumen area, calcium angle, and the maximum calcium thickness. Proportional analysis was used for binary data, and mean difference was used for continuous data. All meta-analyses were conducted using a random-effect model, and 95% CIs were included. A total of 8 observational, single-arm studies, including 980 patients (1,011 lesions), were included; 48.8% of the patients presented with ACS. Severe calcifications were present in 97% of lesions. Clinical success was achieved in 95.4% of patients (95% CI: 92.9% to 97.9%). Angiographic success was achieved in 97% of patients (95% CI: 95% to 99%). There was an overall increase in post-procedural lumen area as well as a significant reduction of calcium angle and maximum calcium thickness. The authors concluded that IVL appeared to have excellent safety and efficacy in the management of CCAD; however, adequately powered RCTs are needed to evaluate IVL compared to other calcium/plaque modifying techniques.
Honton and Monsegu (2022) stated that IVL is a novel approach to lesion preparation for severely calcified plaques in coronary and peripheral vessels. Lithotripsy is delivered by vaporizing fluid to create an expanding bubble that generates sonic pressure waves, which interact with arterial calcification. Available data indicate that IVL leads to increased vessel compliance before stent implantation, demonstrating high efficacy and an excellent safety profile. Since gaining the CE mark in 2017, and with improved operator experience, the use of IVL has expanded into more complex clinical situations. The authors concluded that IVL is a promising therapy for complex calcified lesions, featuring a short learning curve and a favorable safety profile; however, understanding the technical characteristics of the catheter and appropriate considerations regarding preparation, use, and specific conditions for IVL will enhance daily results and outcomes in patients with complex calcified coronary disease.
Sharma (2022) described a case of right coronary artery (RCA) calcifications successfully managed with shockwave intravascular lithotripsy (IVL)-assisted staged percutaneous coronary intervention (PCI). This case involved a 74-year-old male patient who presented with ST-segment elevation myocardial infarction (STEMI). At that time, coronary angiography demonstrated calcific thrombotic occlusion in the left anterior descending artery (LAD) and stenosis in the proximal and mid tubular RCA. It was decided to proceed with immediate PCI of the LAD, followed by staged PCI of the RCA. The patient presented with unstable angina during the second repeat PCI of the RCA and was managed with shockwave IVL-assisted staged PCI. The patient's condition improved, showing good thrombolysis in myocardial infarction (TIMI) flow. The author stated that IVL is a relatively novel technique designed to overcome calcified stenosis in coronary arteries, with promising outcomes from several clinical trials.
Rola et al. (2022) stated that unprotected calcified left main disease represents a high-risk subset for PCI, associated with a higher number of peri-procedural complications and an increased rate of in-stent thrombosis and re-stenosis. Adequate lesion preparation plays a crucial role in achieving favorable PCI outcomes. Rotational atherectomy (RA) is a well-established plaque-modifying method; however, data regarding the effectiveness of RA in left main (LM) diseases are scarce. Recently, the novel ShockWave Intravascular Lithotripsy (S-IVL) device has been introduced to the PCI armamentarium to modify calcified plaque. These researchers conducted a retrospective evaluation of 44 consecutive subjects who underwent LM-PCI, supported by either RA or S-IVL. The Rota group consisted of 29 patients with a mean syntax score of 28.0 ± 7.5, while the S-IVL group was composed of 15 subjects with a syntax score of 23.3 ± 13.0. There were no statistical differences regarding MACE between the RA and Shockwave arms in the in-hospital group (10.3% versus 6.7%) or in the 6-month follow-up group (17.2% versus 13.3%). The authors concluded that RA and S-IVL could be safe and effective therapeutic strategies for calcified LM disease. Moreover, they stated that further studies with a higher number of participants and longer follow-up times are needed to establish the potential benefits of RA and S-IVL for managing LM stenosis. They noted that this was a retrospective, observational, non-randomized pilot study with a relatively short observation period (6-month follow-up). The study population was not large and was underpowered for a reliable assessment of events. Additionally, the rate of intravascular guidance for PCI procedures was comparatively low.
In a retrospective, single-center study, Rao et al. (2022) examined the safety and effectiveness of IVL in managing coronary artery calcification. Patients with hemodynamically stable acute coronary syndrome or symptomatic chronic coronary syndrome (CCS) and calcified coronaries on angiography who underwent IVL were enrolled. Intravascular imaging was performed wherever feasible. The primary endpoint was procedural success, and data regarding procedural complications were collected. A total of 29 patients underwent IVL, with the majority being males and having comorbidities such as hypertension and diabetes. A procedural success rate of 93.1% was achieved, with no patient having greater than 50% residual stenosis. The IVL catheter was successfully delivered in all patients. The mean catheter diameter was 3.3 ± 0.4 mm, and the mean number of delivered pulses was 70.3 ± 16.4. The arteries most commonly intervened were the left main coronary and the left anterior descending artery. Intracoronary imaging revealed a significant increase in minimum luminal cross-sectional area (MLA) post-IVL (pre-MLA: 5.1 ± 2.5 mm²; post-MLA: 10.7 ± 2.9 mm²; p < 0.001). Two patients experienced in-hospital MACE in the form of peri-procedural non-Q-wave MI. No patient had arrhythmias, stent thrombosis, coronary perforation, or slow flow/no-reflow. Two patients had a rupture of the IVL balloon, while four had coronary artery dissection. The authors concluded that IVL was a safe and highly effective modality with a high procedural success rate in managing calcified coronaries. They noted that the limitations of the study included its retrospective design, small sample size, and non-randomized nature with a lack of a comparative control group. Furthermore, a lack of follow-up data and an absence of core laboratory analysis and intravascular imaging for the entire dataset were other limitations.
Kereiakes et al. (2022) stated that coronary calcification impairs stent delivery and optimal expansion, which is a significant predictor of subsequent stent thrombosis and re-stenosis. Current calcium ablative technologies may be limited by guide-wire bias and peri-procedural complications. IVL delivers acoustic pressure waves to modify calcium, enhance vessel compliance, and optimize stent deployment. The Disrupt CAD III study demonstrated high (92.4%) procedural success and low (7.8%) 30-day MACE rates following IVL; however, longer-term follow-up is needed to determine the durability of clinical benefit and the late impact of optimized stent implantation associated with IVL. This analysis evaluated 1-year outcomes from the Disrupt CAD III study. Disrupt CAD III was a prospective, single-arm approval study designed to assess the safety and effectiveness of IVL as an adjunct to coronary stenting in de novo, severely calcified coronary lesions (n = 384). MACE was defined as the composite of cardiac death, MI, or ischemia-driven target vessel revascularization (TVR); target lesion failure was defined as cardiac death, MI, or ischemia-driven target lesion revascularization (ID-TLR). At 1 year, MACE occurred in 13.8% of patients (cardiac death: 1.1%, MI: 10.5%, ischemia-driven TVR: 6.0%), and target lesion failure occurred in 11.9% (ID-TLR: 4.3%), both driven by non-Q-wave MI (9.2%). Stent thrombosis (definite or probable) occurred in 1.1% of patients (including 1 event [0.3%] beyond 30 days). The authors concluded that the Disrupt CAD III represented the largest long-term (1-year) analysis of coronary IVL to date. IVL treatment prior to coronary stent implantation in severely calcified lesions was associated with low 1-year rates of MACE, ID-TLR, and stent thrombosis. Moreover, these researchers stated that further investigation is needed to examine if IVL can effectively reduce the longer-term (beyond 1 year) annualized incidence of adverse stent device-related events in patients with severe target lesion calcification.
The authors stated that this study had several drawbacks. First, Disrupt CAD III was a single-arm study without a randomized comparator or concurrent control arm; as such, comparisons with ORBIT II or other trials should be considered hypothesis-generating. Furthermore, randomized studies would be needed to compare the impact of IVL treatment versus other calcium-modifying technologies on longer-term outcomes. Second, multiple angiographic and patient demographic subsets were excluded per protocol, which limited broader generalization of the observations to a “real-world” all-comers population. These groups included biomarker-positive acute coronary syndromes, severe renal insufficiency, extreme target vessel tortuosity, or unprotected left main, ostial, and saphenous vein bypass graft target lesions. Nevertheless, this study represented the largest clinical trial experience with coronary IVL in patients with severe lesion calcification, who are often excluded from participation in most clinical trials. Similarly, patients with moderately calcified lesions were not included in the present study, and the relative safety and effectiveness of IVL have not been examined in such lesions. Finally, the relationship between the intravascular imaging findings from the Disrupt III OCT sub-study and 1-year clinical outcomes has not yet been analyzed. A larger pooled analysis from the Disrupt CAD study is ongoing and will be better powered to assess these relationships.
Yap et al. (2022) stated that coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. Shockwave intravascular lithotripsy (IVL) has recently been introduced as a new modality to treat heavily calcified coronary arteries. In a prospective, single-center study, these researchers examined the safety and procedural success of IVL in calcified lesions. Intravascular ultrasound (IVUS) was used in all cases to characterize the lesions pre-procedure and to assess procedural success post-procedure. The primary endpoint was procedural success, defined by IVL treatment and successful stent implantation. The secondary endpoint was in-hospital and 30-day MACE. A total of 5 patients with severely calcified lesions were successfully treated with IVL. The primary endpoint was achieved in all patients. All of the lesions were severely calcified with concentric calcium. Multiple calcium fractures were identified on IVUS after IVL in all cases. None of the patients suffered in-hospital or 30-day MACE. The average diameter stenosis at baseline was 1.8 ± 0.4 mm, and the post-PCI diameter stenosis was 2.9 ± 0.1 mm, with a significant acute luminal gain of 1.2 ± 0.3 mm (p < 0.01). There were no complications of coronary dissection, slow or no reflow, stent thrombosis, or vessel perforation. The authors concluded that their initial experience showed the feasibility and safety of IVL in managing calcified coronary stenosis. The shockwave IVL is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with a good success rate and a low rate of complications. Moreover, these researchers stated that this was a prospective, single-arm registry with a short-term follow-up period of 30 days. They noted that larger randomized studies or clinical registries of IVL with long-term follow-up will be of significant clinical value.
Gardiner et al. (2022) stated that coronary artery calcification (CAC) is commonly encountered by interventional cardiologists. Severe CAC may impair stent delivery or result in stent under-expansion, stent thrombosis, and/or in-stent restenosis (ISR). Multiple tools have been developed to help overcome the challenges associated with CAC and improve outcomes for these patients. Intravascular shockwave lithotripsy (IVL) is a novel therapy that uses acoustic pressure waves for the modification of CAC. These researchers discussed the growing body of evidence supporting the safety and effectiveness of IVL in the setting of de novo severely calcified coronary arteries prior to stenting. They also discussed international real-world experience with the coronary IVL system, including its use in the setting of acute coronary syndrome (ACS), ISR, and in combination with other tools for calcium modification. The authors concluded that IVL is a safe and effective therapy that results in the fracture of coronary calcium and facilitates optimal stent delivery and expansion. Moreover, these investigators stated that longer-term follow-up is essential to shed light on the durability and late outcomes of an IVL strategy; RCTs are needed to compare IVL to alternative methods of calcium modification and to further examine the use of IVL for ACS.
The American College of Cardiology/American Heart Association practice guideline on “Coronary artery revascularization” (Lawton et al., 2022) stated that “Fibrotic or heavily calcified lesions can hinder stent expansion. The presence of calcium deposits thicker than 500 μm or calcium involving an arc of the vessel greater than 270° on intravascular imaging predicts the need for lesion modification to facilitate stent delivery. Lesions can be modified by using rotational atherectomy, orbital atherectomy, cutting balloon atherotomy, intracoronary lithotripsy, or excimer laser angioplasty. Despite promising results from hundreds of small mechanistic studies, dozens of large randomized trials have shown that the routine use of athero-ablative devices does not improve clinical or angiographic outcomes.” The guideline rendered a IIb “may be considered” rating for the use of intracoronary lithotripsy for the treatment of fibrotic or heavily calcified lesions.
In a prospective, single-center registry, Yap et al. (2023) examined the procedural success and safety of orbital atherectomy (OA) in calcified lesions. IVUS or optical coherence tomography (OCT) was used in all cases to characterize the severity of calcium pre-procedure, guide vessel sizing, and assess procedural success. The primary endpoint was procedural success, defined by successful stent implantation following OA treatment. The secondary endpoint was in-hospital and 30-day MACE. A total of 10 patients with severely calcified lesions were successfully treated with OA. The primary endpoint was achieved in all patients. All of the lesions were severely calcified with concentric calcium. None of the patients suffered in-hospital or 30-day MACE. The average minimal luminal diameter at baseline was 1.7 ± 0.3 mm, and the post-PCI luminal diameter was 3.0 ± 0.3 mm, with a significant luminal gain of 1.3 ± 0.3 mm (p < 0.01). Slow flow during the procedure occurred in 2 (20%) cases, and dissection occurred in 1 (10%) case during the procedure. These were successfully treated with stent delivery to achieve TIMI III flow. There were no cases of stent thrombosis or vessel perforation. The authors concluded that their experience showed the feasibility and safety of OA in managing calcified coronary stenosis. Intravascular imaging is an important adjunct to the use of OA to assess the severity of calcified coronary lesions, the success of OA treatment, and to aid sizing of the vessel for stent implantation. OA is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with a good success rate and a low rate of complications. These researchers stated that this was a prospective, single-arm registry with a short-term follow-up period of 30 days. They noted that larger, randomized studies or clinical registries of OA with long-term follow-up will be of significant clinical value.
Farhat et al. (2023) stated that the use of rotational atherectomy (RA) and IVL in patients with in-stent restenosis (ISR) is still controversial. In a retrospective, single-center study, these researchers examined the safety and feasibility of RA and IVL in patients with calcified ISR. They also compared in-hospital and 1-year clinical outcomes between both groups. This trial included patients with calcified ISR treated with RA (between 2012 and 2021) and IVL (between 2019 and 2021). In-hospital and 1-year clinical outcomes were compared between IVL and RA patients. A total of 28 patients with ISR who underwent RA were compared with 24 ISR subjects after IVL. The procedural success rate was 100% in both groups. Quantitative coronary analysis revealed a similar degree of stenosis prior (66.4 ± 11.4 versus 68.8 ± 19.7, p = non-significant [NS]), and after the procedure (21.5 ± 20.5 versus 22.8 ± 12.1, p = NS) with no difference in acute luminal gain (1.34 ± 0.60 versus 1.38 ± 0.59, p = NS). There was 1 in-hospital MACE in the RA group. At 1-year follow-up, no difference was observed with respect to MACE rate (14.3% versus 16.7%, p = NS) and target lesion revascularization (TLR) (7.1% versus 12.5%, p = NS). The authors concluded that RA and IVL were safe and feasible techniques for calcified ISR, yielding comparable results at 1-year follow-up. Moreover, these researchers stated that further clinical studies are needed to confirm these findings and shed more light on patient and lesion characteristics associated with the best outcomes.
In a retrospective, single-center study, Sandesara et al. (2023) examined the safety and effectiveness of IVL for the treatment of calcified distal left main (LM) disease. These researchers analyzed the baseline clinical, angiographic, and IVUS characteristics, as well as procedural outcomes of 107 patients who underwent distal LM PCI with IVL (with or without adjunct atherectomy) versus RA alone for plaque modification before stenting. A total of 50 patients underwent calcium modification with IVL with or without adjunct atherectomy, and 57 with RA only. The mean age was 73 years, with a high prevalence of diabetes (58.9%), chronic kidney disease (42.1%), and prior revascularization (coronary artery bypass graft surgery [36.4%] or prior PCI [32.7%]). Acute coronary syndrome was the primary indication for PCI in over 50% of the patients in both groups. Medina 1-1-1 LM bifurcation disease was identified in 64% and 60% of the IVL and RA groups (p = 0.64), respectively. Final minimum stent area in distal LM (greater than 8.2 mm²), ostial LAD (greater than 6.3 mm²), and ostial LCX (greater than 5.0 mm²) were achieved in 96%, 85%, and 89% of cases treated with IVL, respectively; and 93%, 93%, and 100% of cases treated with RA, respectively (LM p = 1.00; LAD p = 0.62; LCX p = 1.00 for difference between the two groups). Procedural success (technical success without in-hospital major adverse events) was achieved in 98% of the IVL group and 86% of the RA-only group (p = 0.04). There were 8 procedural complications (flow-limiting dissection, perforation, or slow/no-reflow) in the RA group compared to four in the IVL group (NS), and 1 patient in the RA group required salvaged mechanical support compared to none in the IVL group. The authors concluded that plaque modification with coronary IVL appeared to be safe and effective for the treatment of severely calcified distal LM lesions compared to RA only. Moreover, these researchers stated that larger randomized studies are needed to confirm these findings.
In a retrospective study, Hesse et al. (2023) examined the feasibility of IVL versus RA in unprotected calcified left main coronary artery (LMCA) disease. These researchers analyzed IVL and RA procedures carried out at a large tertiary hospital in the Northeast of England from January 1, 2019, to April 31, 2022. Major safety and effectiveness endpoints were procedural and angiographic success, defined by stent delivery with less than 50% residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of MACE at 1 year. From a total of 242 patients, 44 had LMCA IVL, 81 had LMCA RA, and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4% of LMCA and 92.2% of non-LMCA cases. Procedural and angiographic success rates were 84% or higher across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases, arrhythmias and cardiac tamponade complicated the procedures, respectively. At 1 year, MACE occurred in 10/44 (22.7%) LMCA IVL, 16/81 (19.8%) LMCA RA, and 25/117 (21.4%) cases (p > 0.05). The authors concluded that IVL was feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Moreover, these researchers stated that its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials (RCTs).
Rola et al. (2023) stated that successful PCI in chronic total occlusion (CTO) improves the long-term outcome in patients with coronary artery disease (CAD). Heavy calcification remains one of the strongest predictors of an unfavorable outcome of PCI. In a case-series study, these researchers examined the effectiveness of shockwave IVL (S-IVL), a novel balloon-based coronary system, in facilitating the modification of calcified coronary lesions. Participants included 5 patients with heavily calcified, undilatable CTO lesions who were treated with S-IVL; they were selected from all consecutive CTO-PCI patients performed at 2 high-volume cardiac centers. The registry included 5 patients who underwent successful CTO S-IVL procedures with an average J-CTO score of 2.6 points. In the short-term follow-up period, including the first 30 days, no cases of acute in-stent thrombosis, target lesion failure, or MACE and cerebrovascular events were noted. The authors concluded that these findings suggested that this approach can be safe and useful in the treatment of complex calcified CTO lesions.
Kereiakes et al. (2023) noted that the Disrupt CAD III Trial was a single-arm study in which IVL was performed in severely calcified coronary lesions in 384 patients at 47 global sites between January 2019 and March 2020. Study design, detailed inclusion criteria, and 1-year outcomes have been previously reported. An independent clinical events committee adjudicated target lesion failure (a composite of cardiac death, target-vessel myocardial infarction [TV-MI], or ID-TLR), MACE (a composite of cardiac death, all MI, or TVR), and stent thrombosis (ST, definite or probable). Kaplan-Meier estimates were used to report event rates with no prespecified formal hypothesis testing. Two-year follow-up was available in 347 patients (90.1%). Target lesion failure at 2 years occurred in 60 patients (16.1%), driven by a 10.3% rate of non-Q-wave TV-MI (creatine kinase-myocardial band greater than 3x upper limit of normal), mostly (6.0%) occurring before 30 days. Two-year ID-TLR and ST occurred in 23 (6.4%) and 5 (1.4%) patients, respectively. A single ST event (definite) occurred beyond 1 year. MACE within 2 years occurred in 70 patients (18.9%), driven by non-Q-wave MI (11.3%), with no Q-wave MI events occurring after 30 days. The present report of the Disrupt CAD III 2-year outcomes represented the largest and longest clinical follow-up after IVL treatment of severe coronary artery calcification (CAC). Despite lesion complexity, rates of serious procedural complications were low, and optimized stent expansion was achieved with low rates of ID-TLR and ST through 2 years, suggesting a durable beneficial impact of percutaneous coronary intervention lesion preparation with IVL. Moreover, these researchers stated that RCTs are needed to examine the relative safety and effectiveness of IVL compared with other calcium-modifying technologies.
Caminiti et al. (2023) highlight the challenges posed by calcified coronary plaque (CCP) for interventional cardiologists, particularly regarding stent underexpansion (SU), which can lead to stent thrombosis and in-stent restenosis. Current methods to address SU associated with heavily calcified plaques include the use of very high-/high-pressure noncompliant balloons, off-label rotational and orbital atherectomy, excimer laser atherectomy, and intravascular lithotripsy (IVL). The authors conducted a systematic review and meta-analysis to investigate the success rate of IVL in treating SU due to CCP, incorporating studies and case reports that utilized IVL for this purpose. The primary endpoint was defined as the successful expansion of the underexpanded stent. A meta-analysis was performed to calculate the proportions of procedural success rates along with their corresponding 95% confidence intervals (CIs), employing random-effects models weighted by inverse variance to account for clinical heterogeneity. The analysis included 13 studies with a total of 354 patients, with a mean age of 71.3 years (95% CI 64.9 to 73.1) and 77% (95% CI 71.2% to 82.4%) being male. The mean follow-up duration was 2.6 months (95% CI 1 to 15.3), and the strategy was successful in 88.7% (95% CI 82.3 to 95.1) of cases. The mean minimal stent area reported in 6 studies increased from a pre-IVL value of 3.4 mm² (95% CI 3 to 3.8) to a post-IVL value of 6.9 mm² (95% CI 6.5 to 7.4). Additionally, the mean percentage of diameter stenosis reported in 7 studies decreased from 69.4% (95% CI 60.7 to 78.2) pre-IVL to 14.6% (95% CI 11.1 to 18) post-IVL, with an intraprocedural complication rate of 1.6% (95% CI 0.3 to 2.9). In conclusion, the "stent-through" IVL plaque modification technique is a safe and effective method for treating SU caused by CCP, demonstrating a high success rate and a low incidence of complications. However, this meta-analysis has limitations, including concerns about meta-regression in studies with small sample sizes and the overall quality of the included studies, which showed some risk of bias. The authors report that while the funnel plot and Egger test indicated asymmetry in the endpoints, the findings remain significant given the random-effects model analysis and the limited data available in prior studies. Additionally, there was considerable variability in follow-up lengths across the studies.
The European Association of Percutaneous Cardiovascular Interventions (EAPCI) addresses management strategies for heavily calcified coronary stenoses, defining this condition and providing consensus statements on procedural treatments. They highlight the importance of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as catheter-based imaging tools that offer complementary assessments of calcified lesions, aiding in the selection of appropriate techniques and devices during percutaneous coronary interventions (PCI). IVUS and OCT enable evaluation of calcium from both cross-sectional and longitudinal perspectives. When a stenosis exhibits a high calcification burden with significant luminal narrowing, the use of adjunctive devices such as rotational atherectomy (RA), orbital atherectomy (OA), or intravascular lithotripsy (IVL) is recommended. IVL is preferred for deeper calcification, while atherectomy is more effective for superficial calcification. The inability to navigate a calcified lesion with an imaging catheter often signals the need for upfront plaque modification techniques. The EAPCI defines extensive calcification on coronary computed tomography angiography (CCTA) as a cross-section with calcium greater than 270°. In their consensus statement, they recommend considering PCI with advanced plaque modification techniques, such as IVL or atherectomy, prior to stent implantation when a high coronary stenosis calcium score (cross-section with calcium >270°) is present on CCTA, particularly when the calcified lesion meets the IVUS or OCT criteria for high calcification burden with lumen narrowing.
Lv et al. (2024) noted that severe coronary artery calcification is associated with low success rates in interventional procedures, peri-operative adverse cardiac events, and poor prognosis, presenting a significant challenge for operators. Existing therapy methods have inherent limitations, such as unsatisfactory balloon crossability and inadequate balloon dilation. The emergence of intravascular lithotripsy (IVL) has heralded a new era in the treatment of calcified lesions by utilizing unfocused acoustic pressure waves to fracture calcification in situ; IVL is the only technology capable of targeting deep calcification. These researchers hypothesized that IVL may have substantial clinical application value and potential prospects. Based on existing clinical evidence of IVL and traditional treatment methods, they discussed the safety and effectiveness of IVL, analyzing precautions and coping strategies in clinical practice. The authors concluded that any technology must continually evolve to achieve optimal practical value, and IVL is no exception. Reducing the crossing profile of the IVL balloon can optimize its crossability, while increasing the length and diameter of a single IVL balloon or the total pulse number can further reduce operational time and costs while expanding its application range. They stated that existing evidence shows IVL has great application prospects and potential value in valvular heart diseases accompanied by calcification, suggesting that IVL may revolutionize the treatment of coronary artery calcification.
In a prospective, multi-center, real-world registry, Rodriguez-Leor et al. (2024) examined the performance of coronary IVL in calcified coronary lesions in a real-life, all-comers setting. The REPLICA-EPIC study prospectively enrolled consecutive patients treated with IVL in 26 centers across Spain. An independent core laboratory conducted the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis of less than 20%, and absence of in-hospital MACE). The primary safety endpoint measured freedom from MACE at 30 days. A predefined sub-study compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. A total of 426 patients (456 lesions) were included, with 63% presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). There were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (the primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients; p = 0.073). The authors concluded that coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but a trend toward higher 30-day MACE compared with patients with CCS. Moreover, they stated that the impact of these favorable initial findings on long-term clinical outcomes has yet to be determined.
The authors acknowledged several drawbacks in this study. First, the non-randomized study design lacked a concurrent control group. Despite this limitation, the study demonstrated a high procedural success rate and a remarkably low peri-procedural MACE rate, even considering the severity of lesion calcification and patient complexity in the study population. These positive outcomes, combined with the ease of use and rapid learning curve associated with IVL, strongly suggest that the technology may play a crucial role in treating complex and high-risk calcified lesions. Second, certain lesions were not suitable for core laboratory analysis for various reasons. In 22 cases, the complexity of the lesions, such as overlapping branches or bifurcation treatment with two stents, made them unsuitable for analysis. In 18 cases, poor quality of the recordings, including the absence of a final angiographic study or only fluoroscopy recording, prevented proper assessment. Additionally, in 14 cases, the recordings were not sent to the core laboratory for analysis. Third, only 43% of lesions were treated with guidance from intracoronary imaging. Although the use of intracoronary imaging is particularly useful in treating calcified lesions, these data reflect real-life use outside the controlled context of clinical trials; in fact, in the Disrupt CAD III Trial, only 100 patients out of 431 had intracoronary OCT imaging.
Butala et al. (2024) stated that calcified coronary lesions pose a challenge for PCIs. Coronary IVL is a novel calcium modification technology approved for commercial use in February 2021; however, little is known regarding its uptake in U.S. clinical practice. These researchers described trends in the use of calcium modification strategies, variations in use across hospitals, and predictors of calcium modification and IVL use in PCI. They included patients from the National Cardiovascular Data Registry CathPCI Registry who underwent PCI between April 1, 2018, and December 31, 2022. These investigators examined trends and hospital variation in calcium modification and IVL use, employing multivariate hierarchical logistic regression to identify predictors of calcium modification and IVL use at hospitals in 2022. Of 2,733,494 PCIs across 1,676 hospitals over 4.75 years, 11.4% were performed with calcium modification. Coronary IVL use increased rapidly from 0% of PCIs in Q4 2020 to 7.8% of PCIs in Q4 2022, accompanied by an overall increase in the use of all calcium modification strategies (11.1% to 16.0%) during this period, with a slight corresponding decrease in coronary atherectomy use (5.4% to 4.4%). In 2022, there was wide variation in IVL use across hospitals (median of 3.86%; IQR, 0% to 8.19%), with IVL being the most common calcium modification strategy in 48% of hospitals. The treating hospital was the strongest predictor of calcium modification (median odds ratio [OR], 2.49; 95% CI: 2.40 to 2.57) and IVL use (median OR, 2.89; 95% CI: 2.74 to 3.04). The authors concluded that the introduction of IVL has changed the landscape of calcium modification use for PCI. There was rapid uptake in the use of coronary IVL after its commercial introduction in the U.S., primarily resulting in an overall increase in calcium modification for PCI, with some displacement of atherectomy. Furthermore, there remains wide variation in calcium modification and IVL use, with the strongest predictor of use being the treating hospital site, which may reflect hospital price sensitivity to costly novel technologies or the selective rollout of IVL. These researchers found evidence of race and sex differences in the use of calcium modification for PCI and the initial use of IVL, which provides insight into the prevalence of calcified lesions in these demographic subgroups and has implications for the equitable rollout of novel technologies in interventional cardiology in the future.
The authors stated that these findings should be interpreted in the context of the following potential drawbacks. First, these results contained data only from hospitals participating in the CathPCI Registry and may not reflect non-participating hospitals; however, more than 90% of hospitals participated in the CathPCI Registry, and it is thought to be nationally representative. Second, granular data on coronary calcification (arc of calcium, degree of calcification, and presence of nodules) or the use of intravascular imaging were not available in the CathPCI database, which could affect the use of calcium modification strategies. However, results were similar when repeated among the subset of patients with severely calcified lesions. Third, this study focused on patients who underwent PCI; however, the degree to which PCI was not attempted in patients with severe coronary calcification, or how the treatment rate of such lesions varied over time, could not be addressed.
Riley et al. (2024) stated that the prevalence of calcification in obstructive coronary artery disease is on the rise; PCI of these calcified lesions is associated with increased short-term and long-term risks. To optimize PCI results, there is an expanding array of treatment modalities devoted to calcium modification before stent implantation. The Society for Cardiovascular Angiography and Interventions put forth an expert consensus document regarding methods to identify types of calcified coronary lesions, a central algorithm to help guide the use of various calcium modification strategies, tips for when using each treatment modality, and a look at future studies and trials for treating this challenging lesion subset. This consensus document noted that IVL may be used in the presence of multiple guide wires (e.g., bifurcation lesions) and may also be advantageous in aorto-ostial lesions. While hemodynamically vulnerable patients may not tolerate repeated or prolonged balloon obstruction of coronary flow during the delivery of IVL therapy, recent data showed the safety and feasibility of IVL in left main coronary artery PCI, with a lower rate of slow flow/no-reflow compared to that with RA or OA. The off-label use of IVL has also been widely adopted in the treatment of stent under-expansion due to calcium, calcific neo-atherosclerosis within the stent, or nodular re-protrusion. The key limitation of the device, as with other balloon-based technologies, is deliverability; however, this can be mitigated with increased guide support via guide shape, guide extensions, buddy wires, or other techniques. Overall angiographic complication rates were less than 0.5%. Moreover, these researchers stated that several RCTs evaluating IVL are underway. The Short-Cut (Shockwave Lithoplasty Compared to Cutting Balloon Treatment in Calcified Coronary Disease Trial; NCT06089135) trial aims to randomize 410 patients with calcified lesions to IVL versus cutting balloon (CB) in two cohorts—those prepared with or without RA. The DECALCIFY (Prospective, Randomized, Controlled, Multicenter Study for the Treatment of Calcified Coronary Artery Lesions With Rotational Atherectomy versus Intravascular Lithotripsy; NCT04960319) trial will randomize 100 patients to IVL versus RA and assess in-hospital MACE and stent expansion by OCT. The SONAR (Shockwave Balloon or Atherectomy with Rotablation in Calcified Coronary Artery Lesions; NCT05208749) multi-center RCT of 170 patients will randomize IVL or RA and assess post-procedural myocardial infarction. The BALI (Balloon Lithoplasty for Preparation of Severely Calcified Coronary Lesions Before Stent Implantation; NCT04253171) RCT will compare IVL with the standard of care (which can include plain balloon angioplasty, CB/scoring balloons, and RA) in 200 patients, with the primary endpoint being strategy failure (failed stent delivery, residual stenosis of 20% or greater, or target vessel failure [TVF]). Finally, the VICTORY (Value of IVL Compared to OPN Non-compliant Balloons for Treatment of Refractory Coronary Lesions; NCT05346068) trial is a non-inferiority RCT to compare the impact of IVL with that of very high-pressure balloon on final stent expansion assessed by OCT in 280 patients with calcified lesions. Furthermore, several multi-center, observational IVL studies are underway. The Intravascular Balloon Lithotripsy in Left Main Stem Percutaneous Coronary Intervention Trial (NCT04319666) aims to follow 50 patients undergoing PCI for intravascular imaging–defined calcified left main disease. The EMPOWER CAD trial (Equity in Modifying Plaque of Women with Under-treated Calcified CAD; NCT05755711) is a post-market, multi-center, single-arm observational study to generate real-world clinical evidence associated with IVL in female patients. Other investigator-initiated, real-world registries examining the role of IVL in calcified coronary lesions are ongoing in various countries.
McEntegart et al. (2024) stated that coronary artery disease (CAD) is the leading cause of death for women, yet they remain under-represented in interventional CAD studies. Women have been shown to be at increased risk of mortality and major adverse events (AEs) after percutaneous coronary intervention (PCI). The poorer outcomes are likely because women are typically diagnosed with CAD later, at an older age, with more comorbidities, and with more challenging anatomy, including smaller vessels and a higher prevalence of coronary artery calcification. The EMPOWER CAD trial is a post-market, prospective, observational, single-arm, multi-center study of the Shockwave coronary intravascular lithotripsy (IVL) system for the treatment of women with calcified CAD. The study will enroll 400 female patients referred for PCI with coronary IVL and stenting. The primary safety endpoint is target lesion failure (TLF) at 30 days, defined as a composite of cardiac death, target-vessel myocardial infarction (TV-MI), or ischemia-driven target lesion revascularization (TLR). The primary effectiveness endpoint is procedural success, defined as stent delivery with a residual in-stent stenosis of 30% or less in all target lesions and without in-hospital TLF, as assessed by an independent core laboratory and clinical events committee. Patients will be followed for 3 years. The authors concluded that the EMPOWER CAD study will enroll real-world female patients. Adjunctive use of IVL with other calcium modification technologies will be assessed, as well as a sub-cohort analysis of patients with OCT imaging. The EMPOWER CAD trial, therefore, directly addresses the under-representation of women in interventional cardiology clinical trials.
Sagris et al. (2024) state that intravascular lithotripsy (IVL) technology disrupts both superficial and deep calcium using localized pulsative sonic pressure waves, making it a promising tool for patients with severe calcification in the coronary arteries. The authors conducted a systematic review and meta-analysis of studies assessing the characteristics and outcomes of patients undergoing IVL prior to stent implantation. The analysis included the diameter of the vessel lumen before and after IVL, as well as after stent implantation, and the occurrence of major adverse cardiovascular events (MACE) was evaluated using a random-effects model. This meta-analysis comprised 38 studies involving 2,977 patients with heavily calcified coronary lesions, with a mean age of 72.2 ± 9.1 years. The overall clinical success rate of IVL was 93% (95% confidence interval [CI]: 91%-95%, I² = 0%), and the procedural success rate was 97% (95% CI: 95%-98%, I² = 73.7%). The in-hospital and 30-day incidences of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I² = 84.5%), 5% (95% CI: 2%-8%, I² = 85.6%), and 2% (95% CI: 1%-3%, I² = 69.3%), respectively. There was a significant increase in vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I² = 96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I² = 97.5%) immediately after IVL application. Further reductions in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I² = 95.8%) and increases in vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I² = 96.7%) and calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I² = 98%) were observed after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated at 1.27 ± 0.6 mm and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with only a few cases of perforations, dissections, or no-reflow phenomena recorded. The authors acknowledged several limitations in their study including high heterogeneity in the results, retrospective studies that lacked direct comparisons with other lesion preparation strategies, as well as variations in follow-up. Additionally, the analysis pooled patients from different countries and health systems with varying socioeconomic and ethnic backgrounds, without accounting for the experience of the operators. Furthermore, there were no studies comparing IVL with other techniques to assess its long-term effectiveness. The authors concluded that IVL appears to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries, and they advocate for future prospective studies to compare IVL with other lesion preparation strategies.
Oliveri et al. (2025a) examined the technical success and 1-year clinical outcomes in calcified left main (LM) coronary artery lesions treated with IVL. Patients who underwent IVL from the ongoing prospective BENELUX registry were eligible for inclusion. Subjects were divided into LM and non-LM groups based on the anatomical application of the IVL pulses. The primary technical endpoint was technical success, defined as the successful delivery of the IVL catheter across the target lesion, administration of IVL pulses without angiographic complications, and attaining a residual target lesion stenosis of less than 30%. The primary safety endpoint was in-hospital MACE. The study included 509 patients (59 LM and 450 non-LM). Patients in the LM group were significantly older (79 years [75 to 82] versus 73 years [68 to 81], p < 0.01), and left ventricular ejection fraction (LVEF) was slightly lower in the LM group (41% [19 to 50] versus 51% [40 to 60], p = 0.053). Temporary mechanical circulatory support devices were more frequently used in the LM group, primarily as part of the "protected PCI" strategy (6.8% in LM versus 2.1% in non-LM, p = 0.04). Technical success was comparable between the two groups (93.2% in LM versus 89.8% in non-LM, p = 0.41). Cardiac death, MACE, and target vessel revascularization (TVR) rates were also comparable at hospital discharge, 30 days, and 1-year follow-up. The authors concluded that IVL in calcified LM lesions achieved comparable technical success and long-term clinical outcomes to non-LM lesions.
The authors stated that this study had several drawbacks. First, although beyond the scope of this trial, a direct comparison between IVL and other calcium modification devices would be desirable to better contextualize IVL's relative safety and effectiveness in LM-PCI. Second, despite the high use of intracoronary imaging, heterogeneity between the groups may have influenced these findings. Third, the limited sample size, as well as loss at follow-up, reduced the statistical power and robustness of the conclusions regarding long-term clinical outcomes.
In an observational registry study, Oliveri et al. (2025b) examined the procedural and clinical outcomes of IVL in treating patients with heavily calcified acute coronary syndrome (ACS). Patients who underwent IVL between 2019 and 2024 from the ongoing prospective BENELUX registry were eligible for inclusion. Subjects were classified into ACS and chronic coronary syndrome (CCS) groups. The primary technical endpoint was angiographic success of less than 30%, defined as the successful delivery of the IVL catheter across the target lesion and delivery of IVL pulses without angiographic complications and residual target lesion stenosis of less than 30%. The primary clinical endpoint was in-hospital MACE, including cardiac death, non-fatal MI, or TLR. A total of 454 patients underwent IVL, with 251 (55.3%) treated for CCS and 203 (44.7%) for ACS. The median SYNTAX score (p-value 0.17), the need for inotropes (p-value 0.09), and the use of mechanical circulatory support (p-value 0.71) were similar between CCS and ACS groups. Comparable angiographic success (less than 30% residual stenosis) was observed between CCS and ACS groups (90.1% versus 91.1%, p = 0.69). MACE rates were similar across groups during hospital stays (CCS 1.6% versus ACS 3.0%, p = 0.33), at 30 days (CCS 3.2% versus ACS 3.9%, p = 0.86), and at 12-month follow-up (CCS 8.4% versus ACS 7.9%, p = 0.91). The authors concluded that IVL provided high procedural success and consistent clinical outcomes in both CCS and ACS cases.
The authors stated that this study had several drawbacks. First, its observational nature may introduce inherent biases. Second, paired intracoronary imaging data (before and after IVL) were not available in all patients, potentially negatively impacting stent and clinical outcomes. Third, patient loss at long-term follow-up (lower statistical power) may represent another important limitation.
Meijer et al. (2025) noted that coronary artery bypass grafting (CABG) is a cornerstone treatment for CAD, with the use of saphenous vein grafts (SVGs) being prevalent. However, SVGs are susceptible to high failure rates due to graft inflammation, intimal hyperplasia, and atherosclerosis, resulting in a substantial number of patients requiring revascularization. Percutaneous coronary intervention of SVGs poses unique challenges, including an increased risk of distal embolization and perforation due to the grafts' structure and atherosclerotic nature. The role of IVL in calcific SVG lesions has not been elucidated. In a retrospective, case-series study, these investigators analyzed four cases of patients treated with IVL for SVG stenosis at Leiden University Medical Centre between May 2019 and December 2023. Quantitative coronary analysis and IVUS were employed to evaluate procedural success, and mid- to long-term clinical outcomes were reported as well. In all four cases, IVL was carried out in-stent (two due to calcific in-stent neo-atherosclerosis; two bail-out due to extrinsic stent calcification). No MACE were reported during mid- to long-term follow-up. The procedure showed effective calcium cracking, resulting in optimal stent expansion and minimal residual stenosis with a low risk of procedural complications. The authors concluded that IVL represents a promising approach for managing calcified peri-stent SVG lesions, showing potential for safe and effective revascularization with minimal complications. These researchers stated that these results suggest that IVL could be incorporated into the treatment paradigm for calcified peri-stent SVG stenosis, warranting further investigations in larger, prospective, multi-center studies to validate its safety and effectiveness.
The authors stated that this study had two main drawbacks. First, potential bias may arise from the selective treatment of lesions with PCI of the SVG rather than PCI of the native vessel. This selection process introduced the possibility of bias, as lesions deemed too risky or severe for PCI were excluded from consideration and consequently not included in this report. Second, the limited number of cases (n = 4) compromised the evidential value of these findings.
In an UpToDate review on “Specialized revascularization devices in the management of coronary heart disease”, Cutlip (2025) states that “The safety and efficacy of shockwave intravascular lithotripsy for the treatment of severe coronary artery plaque were established with the DISRUPT CAD II study. In this study, 120 patients were enrolled, with severe coronary artery calcium present in 94% of lesions. Catheter delivery was successful in all patients. Post-procedure, coronary artery residual stenosis was on average 33%, which decreased to 8% following drug-eluting stent implantation. There were no acute procedural complications of major dissections, perforations, abrupt closure, or slow flow/no reflow. Adverse events occurred in 6% in-hospital (non-ST-elevation myocardial infarction) and 8% at 30 days (cardiac death, myocardial infarction, or target vessel revascularization). A potential limitation of the study was that only 6% of participants were female, somewhat limiting the generalizability of the results. A specialized revascularization device is an uncommonly needed tool with specialized functions that can be used at the time of percutaneous coronary intervention (generally before the stent is placed) that either allows for optimal placement of a stent or improved outcomes. Neither short- nor long-term benefits have been shown consistently with the routine use of these revascularization devices. In particular, atherectomy devices have generally failed to improve patient survival or the durability of the revascularization. These findings indicate that the routine use of specialized device therapies (over the combination of balloon dilation and stent implantation) is not justified in most cases.” Furthermore, shockwave intravascular lithotripsy is not mentioned as a therapeutic tool in the “Summary and Recommendations” section of this UTD review.
Suruagy-Motta et al. (2025) highlight that severe coronary artery calcification (CAC) poses a significant challenge in interventional cardiology, particularly for elderly patients and those with comorbidities such as diabetes or chronic kidney disease. CAC can lead to complications like stent thrombosis and restenosis, resulting in poor clinical outcomes and increased rates of major adverse cardiovascular events (MACE). Traditional treatments, such as rotational atherectomy (RA), are often complicated by procedural difficulties, extended procedure times, and risks of vascular injury. In contrast, intravascular lithotripsy (IVL) has emerged as a novel therapy that utilizes acoustic pressure waves to fracture calcified plaques with minimal vascular trauma. However, there is a lack of direct comparisons between IVL and RA in the context of severe CAC, creating critical gaps in evidence for optimizing therapy. This study aims to compare the clinical outcomes, including procedural success, safety, and efficacy, of IVL and RA in treating severe CAC. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines, with searches performed in multiple databases for studies that directly compared IVL and RA. Eleven studies involving 2,120 patients were included, revealing that IVL offered significant advantages over RA, such as reduced contrast use (mean difference [MD]: -17.45 mL) and shorter procedural times (MD: -27.90 min). IVL effectively treated complex lesions, including bifurcations and calcified left main arteries, with minimal vascular trauma and lower procedural risks. Although luminal gain did not differ significantly between the two groups (MD: -0.07 mm²), IVL demonstrated higher rates of stent deployment success and lower target lesion revascularization, suggesting better long-term vessel patency. The meta-analysis indicated a pooled odds ratio for mortality of 0.55 under the common-effect model and 0.70 under the random-effects model, with negligible heterogeneity. These consistent findings support IVL as a safer and more effective strategy for managing severe CAC, warranting further trials to confirm long-term benefits. The authors concluded that IVL presents slight advantages over RA in treating severe CAC, including reduced contrast use, shorter procedure times, and fewer complications, highlighting the need for additional studies to validate these results and address study heterogeneity.
Moghadam et al. (2025) address the significant challenges posed by calcific coronary lesions in percutaneous coronary intervention (PCI), which can hinder stent delivery and expansion. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are commonly employed plaque modification techniques, yet comparative data on their effectiveness are limited. Their study aimed to evaluate and compare the clinical and procedural outcomes of IVL and RA in managing calcific coronary lesions. A comprehensive search of PubMed, Embase, Scopus, and the Cochrane Library was conducted through January 2025, focusing on randomized controlled trials (RCTs) and observational studies that compared IVL with RA in this context. The primary outcome assessed was major adverse cardiovascular events (MACE), while secondary outcomes included all-cause mortality, myocardial infarction (MI), stroke, repeat revascularization, procedural outcomes, and minimum stent area (MSA). The analysis included 14 studies (2 RCTs and 12 observational studies) with 2,056 patients treated with IVL and 3,099 with RA. The results indicated that IVL and RA had comparable risks of MACE (odds ratio [OR] 0.81; 95% confidence interval [CI] 0.57-1.16; p = 0.26) and similar rates of all-cause mortality, MI, stroke, and repeat revascularization. However, IVL was associated with a significantly lower risk of coronary perforation (OR 0.43; 95% CI 0.32-0.57; p < 0.001) and slow or no-reflow (OR 0.34; 95% CI 0.14-0.79; p = 0.02). Additionally, IVL resulted in shorter procedure durations (standardized mean difference [SMD] -0.30; 95% CI -0.61 to 0.00; p = 0.05) and reduced fluoroscopy times (SMD -0.41; 95% CI -0.62 to -0.20; p = 0.004). Post-procedural MSA was found to be similar between the two techniques. The authors concluded that while IVL and RA demonstrated comparable efficacy regarding MACE and clinical outcomes in patients with calcific coronary lesions undergoing PCI, IVL showed advantages such as a lower risk of coronary perforation, reduced slow or no-reflow phenomena, and shorter procedure and fluoroscopy times, indicating a potential procedural benefit over RA.
Kristensen, et al. (2025) reported the results of the BALI trial, a randomized, assessor‑blinded, multicenter study designed to determine whether adding intravascular lithotripsy to conventional lesion preparation improves outcomes in patients undergoing PCI for severely calcified coronary lesions. Investigators enrolled 200 adults with chronic coronary syndrome or non‑ST‑segment elevation acute coronary syndrome and angiographically or intravascularly confirmed severe calcification. Participants were randomized 1:1 to receive either lithotripsy plus conventional lesion preparation or conventional preparation alone before implantation of a second‑generation drug‑eluting stent. All procedures were guided by mandatory optical coherence tomography (OCT), and outcomes were assessed using intention‑to‑treat principles. The primary composite endpoint included procedural failure (defined as failed or no stent delivery or residual in‑stent area stenosis ≥20%) or target vessel failure, a combination of cardiac death, target‑vessel myocardial infarction, and clinically driven target‑vessel revascularization at 1 year. The study found that lithotripsy significantly reduced the primary composite endpoint, occurring in 35% of patients assigned to lithotripsy compared with 52% receiving conventional preparation alone (RR 0.69; P = 0.02). This improvement was driven mainly by reductions in residual area stenosis ≥20%, which occurred in 32% vs 45% of patients, respectively. Rates of target vessel failure also numerically favored lithotripsy (4% vs 11%), although the difference was not statistically significant. Safety outcomes, including periprocedural myocardial infarction, flow‑limiting dissection, perforation, and 1‑year adverse events, were similar between groups. OCT analyses demonstrated modest improvements in minimal stent expansion and minimal stent area at the site of maximal calcification in the lithotripsy arm. Importantly, late lumen loss at 1 year was comparable across both groups, suggesting no adverse long‑term remodeling associated with lithotripsy. Study limitations include the composite nature of the primary endpoint, heavily influenced by residual area stenosis, a measure dependent on reference‑area selection. Although OCT adjudication was blinded with predefined criteria, small differences in reference sizing could influence results. The trial was conducted at high‑volume European centers by operators experienced in calcium modification and imaging‑guided PCI, potentially limiting generalizability to broader practice settings. Additionally, subgroup analyses were underpowered and exploratory. Despite these limitations, the investigators concluded that the trial demonstrated that adding lithotripsy to standard lesion preparation improves procedural and 1‑year anatomical outcomes without compromising safety, supporting its role in treating severely calcified coronary lesions.
The EMPOWER CAD study (McEntgart, et al., 2026) was a prospective, multicenter, single‑arm real‑world investigation designed to evaluate the safety, effectiveness, and quality‑of‑life impact of an intravascular lithotripsy (IVL)–first strategy in women undergoing percutaneous coronary intervention for severely calcified coronary artery disease. Its objective was to address the persistent underrepresentation of women in prior plaque‑modification and PCI trials and to characterize outcomes in this high‑risk population. The study enrolled 399 women with extensive comorbidities and complex lesion characteristics, nearly all of whom had severe coronary calcification. Participants were treated primarily with IVL as the first calcium‑modifying therapy, and the primary safety endpoint, 30‑day target lesion failure, was assessed as a composite of cardiac death, myocardial infarction, or ischemia‑driven target lesion revascularization. Effectiveness was evaluated based on successful stent delivery with adequate residual stenosis reduction and absence of in‑hospital target‑lesion failure. Results demonstrated high procedural success (87.4%) and substantial angiographic improvement, with mean diameter stenosis decreasing from 78% at baseline to 12% in‑stent at the final angiogram. Thirty‑day target lesion failure occurred in 11.6% of patients, driven largely by periprocedural myocardial infarction, more than half of which consisted of asymptomatic biomarker elevations identified through systematic laboratory testing. Serious angiographic complications were rare, and quality‑of‑life measures (including angina, general health status, and anxiety) improved significantly by 30 days. Despite these strengths, the study’s single‑arm design without a comparison group limited its ability to evaluate relative efficacy versus other plaque‑modification strategies or outcomes in men. Lack of blinding may have introduced bias into patient‑reported measures, and the predominance of IVL as the chosen strategy limited insights into how outcomes might differ with alternative adjunctive devices. Nonetheless, the authors concluded that the study provides important evidence supporting an IVL‑first approach in women with complex calcified CAD, while underscoring the need for randomized trials to compare treatment strategies more definitively.
Badrawy Khalefa et al. (2026) discuss the significant challenge posed by coronary stenosis with severe calcification in percutaneous coronary intervention, as calcified coronary arteries hinder stent expansion and catheter passage, leading to increased complications such as target lesion failure, stent thrombosis, and cardiac mortality. Various modalities for calcium modification, including intravascular lithotripsy (IVL) and rotational atherectomy, have been proposed, and this study aims to compare the effectiveness of both techniques in treating calcified coronary artery disease. A systematic search of PubMed, Scopus, Cochrane, and Web of Science was conducted from inception to January 2025, with dichotomous outcomes pooled as odds ratios (OR) and continuous outcomes pooled as mean differences, along with their respective 95% confidence intervals (CI). The primary endpoint was major adverse cardiovascular events (MACE) during hospitalization and the longest reported follow-up, while procedural success was a key secondary endpoint. The analysis included 15 studies (1,406 patients undergoing rotational atherectomy and 1,088 patients undergoing IVL), revealing no significant difference in MACE during hospitalization (OR = 1.43; 95% CI: 0.63-3.22) or at the longest follow-up (OR = 0.93; 95% CI: 0.44-2.00). However, procedural success favored IVL (OR = 0.57; 95% CI: 0.36-0.89), and safety endpoints also favored IVL, as rotational atherectomy was associated with a higher risk of coronary perforation (OR = 2.67; 95% CI: 1.58-4.49) and slow flow/no-reflow (OR = 2.49; 95% CI: 1.03-6.03). There were no differences in mortality, myocardial infarction, target vessel revascularization, or stent thrombosis between the two techniques, but IVL resulted in shorter procedure durations (mean difference: 13.79 minutes; 95% CI: 4.09-23.49). In conclusion, both IVL and rotational atherectomy are effective options for plaque modification in calcified coronary artery lesions prior to drug-eluting stent implantation, with comparable clinical safety and efficacy outcomes. While IVL demonstrated higher procedural success and fewer complications, its higher costs present a significant drawback that may limit its widespread adoption and standardization in clinical practice.
Cerrato et al. (2026) note the lack of prospective data on the contemporary use of various coronary calcium debulking techniques. The authors aimed to compare intravascular lithotripsy (IVL) with atherectomy (AT) devices, including both rotational and orbital atherectomy, in a real-world all-comer population. The ROLLING STONE Registry prospectively enrolled patients treated with IVL and/or AT across 23 Italian centers, with the primary efficacy endpoint defined as procedural success (residual stenosis <30% and absence of in-hospital major adverse cardiac events [MACE], such as cardiac death, myocardial infarction, and target vessel revascularization). The primary safety endpoint was freedom from MACE at 30 days, while the secondary endpoint assessed MACE at 12 months. Propensity score matching and inverse probability weighting were utilized to compare safety endpoints. A total of 1,005 patients were enrolled, with 544 (59%) in the IVL group and 380 (41%) in the AT group, excluding 81 patients who received both treatments. The primary efficacy endpoint was similar between groups (85.4% for IVL vs. 86.3% for AT; relative risk: 1.01; 95% CI: 0.88-1.17). However, the MACE rate at 30 days was significantly lower in the IVL group (5.7% vs. 8.6%; hazard ratio [HR]: 0.60; 95% CI: 0.36-0.99; P = 0.045), primarily due to a lower rate of cardiovascular death (1.7% vs. 3.9%; HR: 0.40; 95% CI: 0.18-0.92; P = 0.030). After applying propensity score matching (n = 320) and inverse probability weighting (n = 532), the MACE rate at 12 months was also significantly lower in the IVL group (6.8% vs. 14.3%; HR: 0.43; 95% CI: 0.21-0.89; P = 0.022). The study confirms the feasibility, safety, and efficacy of both IVL and AT in an unselected population, with similar procedural success rates; however, after propensity matching, IVL appears to offer better safety outcomes at 12 months. The authors acknowledged several limitations, including the nonrandomized nature of the study, which may overlook certain clinical or procedural variables related to outcomes. They noted that the rationale for selecting a specific calcium modification device was not systematically recorded, limiting the analysis of factors influencing device selection. Additionally, the absence of systematically collected quantitative calcium scores using advanced imaging techniques restricted the ability to stratify outcomes by calcium severity. The AT group included patients treated with both rotational and orbital atherectomy, which may introduce variability in outcomes due to differences in their mechanisms of action. Furthermore, the study did not include excimer laser debulking, and comparisons with other plaque modification strategies were not made. The use of intracoronary imaging was limited, reflecting real-world practices, and the application of propensity score matching reduced the sample size, potentially affecting the statistical power for detecting subtle differences. Despite these limitations, the authors concluded that this study demonstrated a high procedural success rate even in high-risk patients and complex anatomical settings, which are often excluded from registries.
Abciximab for Thrombus Resolution During Intracranial Bypass Surgery
Buchanan and colleagues (2018) noted that abciximab is a glycoprotein IIb/IIIa receptor antagonist that functions to prevent platelet aggregation, thus reducing thrombus initiation and propagation. The use of abciximab in cardiac and neurosurgical procedures has been associated with a reduced incidence of ischemic complications and a decreased need for repeated intervention. In these settings, abciximab has been delivered trans-arterially via a micro-catheter or infused intravenously for systemic administration. In a case-report, these investigators described novel in-situ delivery of abciximab as an agent to dissolve "white clots", which are composed primarily of platelets, during an intracranial superficial temporal artery to middle cerebral artery bypass in a 28-year old woman with severe intracranial occlusive disease. Abciximab was able to resolve multiple platelet-based clots after unsuccessful attempts with conventional clot dispersal techniques, such as heparinized saline, tPA, mechanical passage of a wire through the vessel lumen, and multiple take-downs and re-anastomosis. After abciximab was administered, patency was demonstrated intra-operatively using indocyanine green (ICG) dye and confirmed post-operatively at 1 and 10 months via CT angiography. The authors concluded that the in-situ use of abciximab as an agent to disperse a thrombus during intracranial bypass surgery is novel and has not previously been described in the literature, and serves as an additional tool during intracranial vessel bypass surgery.
Abciximab / Heparin Therapy for Left Ventricular Assist Device Implantation in Patients with Heparin-Induced Thrombocytopenia
Lee and associates (2018) stated that the optimal anti-coagulation strategy remains uncertain in patients with heparin-induced thrombocytopenia (HIT) undergoing left ventricular assist device (LVAD) implantation. These researchers described their protocol of abciximab and heparin in these patients. The protocol was to administer abciximab, 0.25 mg/kg loading dose, followed by continuous infusion of 0.125 μg · kg-1 · min-1 throughout cardio-pulmonary bypass. Full-dose heparin was then given with subsequent additional doses to maintain an activated clotting time of 400 seconds or longer. The abciximab infusion was stopped 15 minutes after heparin reversal with protamine, and platelets were transfused. A total of 6 patients underwent LVAD implantation with this protocol in the authors’ program; HIT was confirmed in 4 patients; it was suspected in 2, which was negative after the operation; 1 patient received a HeartMate XVE and the others received HeartMate II. There were no thromboembolic complications; 1 patient required chest re-exploration for bleeding and temporary right VAD support. Post-operative anti-coagulation with argatroban was re-started on median post-operative day 3 (range of days 1 to 6), and warfarin was started on day 5 (range of days 3 to 12). Median post-operative ICU stay was 9 days (range of 5 to 76), and hospital stay was 22 days (range of 18 to 132). After the initial LVAD implantation, 1 patient required HeartMate XVE LVAD exchange to HeartMate II and subsequent heart transplant, both of which were performed with the abciximab/heparin protocol. A HeartMate II device was explanted in another patient after myocardial recovery. The remaining 4 patients were alive on device support. The authors concluded that this was the first report of a novel abciximab/heparin protocol for LVAD implantation in patients with HIT. They stated that these preliminary findings suggested the feasibility and safety of this protocol. They stated that further studies in the use of this protocol in HIT patients requiring cardiac operations are needed.
The authors stated that this study had several drawbacks. First, this is a retrospective study, and the sample number was limited (n = 6). Second, there was no control group to compare the peri-operative outcomes. Moreover, there were 2 patients without serotonin release assay testing, albeit with strong clinical evidence supporting the diagnosis of HIT.
Acute Ischemic Stroke
Al-Mufti and colleagues (2017) retrospectively delineated the feasibility of the combined use of emergent carotid stenting and intra-arterial (IA) abciximab with intracranial re-vascularization in the setting of acute ischemic stroke and carotid occlusions. A total of 11 patients with complete cervical carotid occlusion with or without concomitant intracranial ICA and/or MCA occlusion were identified from a single center, retrospective review of patients admitted to the Stroke unit. These researchers evaluated all cases for complications of emergent cervical ICA recanalization employing carotid stenting and IA abciximab. All patients had complete cervical carotid occlusion with (n = 8) or without (n = 3) concomitant intracranial ICA and/or MCA occlusion. Successful emergent cervical ICA re-canalization was achieved in all cases. All patients were administered IA abciximab (dose range 6 to 17 mg, average of 11.4 mg) immediately following the cervical carotid stenting. There was complete re-canalization in all patients with no procedural morbidity or mortality. A single case (1/11, 9%) developed asymptomatic hemorrhagic transformation. Upon discharge, 9 patients (9/11, 82%) had a modified Rankin Scale (mRS) of 0 to 2, and 2 patients (2/11, 18%) had a mRS of 3. The authors concluded that in acute ICA-MCA/distal ICA occlusions, extracranial stenting followed by intracranial IA abciximab and thrombectomy appeared feasible, safe, and effective. They stated that further evaluation of this treatment strategy is needed.
Acute Limb Ischemia
Salzler et al. (2016) stated that contemporary endovascular management of acute limb ischemia (ALI) generally consists of tissue plasminogen activator (tPA) based catheter-directed thrombolysis (CDT) with or without pharmaco-mechanical thrombectomy (PMT). Although abciximab is widely used in coronary re-vascularization, its safety and effectiveness in the treatment of ALI are unknown. These investigators reviewed their contemporary experience with the endovascular management of ALI and evaluated the safety and effectiveness of abciximab. A total of 49 consecutive patients with Rutherford class II (RII) ALI undergoing CDT for ALI from 2011 to 2014 was identified. Demographics, procedural details, and outcomes were assessed and reported. A total of 44 patients with RII ALI underwent tPA-based CDT in 49 discrete interventions. In 11 patients adjunctive abciximab infusion was also used. The majority (82%) of patients treated with tPA ± PMT required over-night infusion and at least 1 subsequent procedure. Single-stage (on-table) thrombolysis was achieved in 91% of cases with adjunctive abciximab use versus 18% with tPA alone (p < 0.001). There was significantly less need for intensive care unit (ICU) monitoring, and there were no bleeding complications associated with adjunctive abciximab use. Overall length of stay and total operating room time favored the abciximab group; but did not reach statistical significance. Overall primary patency, secondary patency, and amputation-free survival were 46 ± 9.9%, 79 ± 6.6%, and 78 ± 9.2%, respectively, at 1 year. The authors concluded that early results suggested adjunctive abciximab may safely facilitate on-table thrombolysis for RII ALI. This approach appeared to be associated with reduced resource utilization including fewer procedures, shorter operating room time, and less ICU admissions and 1-year outcomes compared favorably to a similar cohort of ALI patients treated with tPA-based therapy alone. These findings from a small study (only 11 subjects received abciximab) need to be validated in well-designed studies.
Adjuvant Abciximab in ST-elevation Myocardial Infarction
Caldeira and colleagues (2019) stated that the standard of care for acute STEMI includes the activation of a STEMI care network, the administration of adjuvant medical therapy, and re-perfusion through primary PCI. While primary PCI is nowadays the first option for the treatment of patients with STEMI, anti-thrombotic therapy, including anti-platelet and anti-coagulant agents, is the cornerstone of pharmacotherapies to optimize their clinical outcomes. These researchers described contemporaneous real-world patterns of use of anti-thrombotic treatments in Portugal for STEMI patients undergoing primary PCI. They carried out a retrospective, observational, cross-sectional study for the year 2016, based on data from 2 national registries: the Portuguese Registry on Acute Coronary Syndromes (ProACS) and the Portuguese Registry on Interventional Cardiology (PRIC). Data on oral anti-platelet and procedural IV anti-thrombotic drugs were retrieved. In 2016, the ProACS enrolled 534 STEMI patients treated with primary PCI, while the PRIC registry reported data on 2,625 STEMI patients. Of these, 99.6% were treated with aspirin, 75.6% with dual anti-platelet therapy (mostly clopidogrel), and GPIs (mostly abciximab) were used in 11.6% of cases. Heparins were used in 80% of cases (78% un-fractionated heparin [UFH] and 2% low molecular weight heparin [LMWH]). None of the patients included in the registry was treated with cangrelor, prasugrel, or bivalirudin. Missing data were one of the main drawbacks of the registries. The authors concluded that in 2016, according to data from these national registries, almost all patients with STEMI were treated with aspirin and 76% with dual anti-platelet agents, mostly clopidogrel; however, GP IIb/IIIa inhibitors (mostly abciximab) were used in few patients, and UFH was the most prevalent parenteral anti-coagulant drug.
Karathanos and associates (2019) examined the effectiveness of routine use of GPIs in STEMI treated with primary PCI. Online databases were searched for RCTs of routine GPIs versus control therapy in STEMI. Data from retrieved studies were abstracted and evaluated in a comprehensive meta-analysis. A total of 21 RCTs with 8,585 patients were included: 10 trials randomized tirofiban, 9 abciximab, 1 trial eptifibatide, and 1 trial used abciximab + tirofiban; only 1 trial used dual anti-platelet therapy with prasugrel/ticagrelor. Routine GPI use was associated with a significant reduction in all-cause mortality at 30 days (2.4% [GPI] versus 3.2%; RR, 0.72; p = 0.01) and 6 months (3.7% versus 4.8%; RR, 0.76; p = 0.02), and a reduction in recurrent MI (1.1% versus 2.1%; RR, 0.55; p = 0.0006), repeat re-vascularization (2.5% versus 4.1%; RR, 0.63; p = 0.0001), thrombolysis in MI flow less than 3 after PCI (5.4% versus 8.2%; RR, 0.61; p < 0.0001), and ischemic stroke (RR, 0.42; p = 0.04). Major (4.7% versus 3.4%; RR, 1.35; p = 0.005) and minor bleedings (7.2% versus 5.1%; RR, 1.39; p = 0.006) but not intra-cranial bleedings (0.1% versus 0%; RR, 2.7; p = 0.37) were significantly increased under routine GPI. The authors concluded that routine GPI administration in STEMI resulted in a reduction in mortality, driven by reductions in recurrent ischemic events; however, predominantly in pre-prasugrel/ticagrelor trials. These researchers stated that studies with contemporary STEMI management are needed to confirm these findings.
Cardiac Complications (e.g., Coronary Artery Aneurysms) of Kawasaki Disease
Bachlava and co-workers (2016) stated that there are limited data regarding the possible benefits of abciximab in children with Kawasaki disease (KD), who developed serious cardiac abnormalities non-responsive to standard treatment. These investigators retrospectively identified children with KD who were treated with abciximab from 2007 to 2015. Data regarding clinical course, treatment, echocardiographic data and follow-up at 1 and 6 months were retrieved. During the study period, a total of 15 children were identified who were diagnosed with KD and were given abciximab. The median age at onset of symptoms was 11 months (range of 2 months to 6 years). The median day of disease at admission was 10 days (range of 4 to 26 days) and the median day of administration of abciximab was 17 days (range of 9 to 40 days); 12 children were diagnosed with complete and 3 with incomplete KD. Aneurysms were found in 8 children: 2 had ectatic coronary arteries and 5 presented with both ectasia and aneurysms. At 1month follow-up, echocardiographic findings showed regression in the size of aneurysms in 11 children, resolution of the aneurysms or ectasia of coronary arteries in 3 children, while 1 child who could not take aspirin because of G6PD deficiency died. At 6 months of follow-up, echocardiographic findings showed resolution of coronary abnormalities in 12 (80%) children, whereas 2 children (13.3%) presented with significant regression of aneurysms. The authors concluded that abciximab may have an important role in the management of severe cardiac complications of KD, although prospective RCTs are needed to fully evaluate its role.
Intracoronary Brachytherapy for the Treatment of Recurrent Drug-Eluting Stent In-Stent Restenosis
Meraj and colleagues (2021) stated that intracoronary brachytherapy (ICBT) is an effective treatment for ISR of BMS; however, its use has waned due to the advent of DES. In-stent restenosis following drug eluting stents (DES) occurs at a frequency of 8% or greater. In a retrospective analysis, these investigators reported on the safety, short-term and long-term efficacy following ICBT for ISR in patients with DES. This analysis was carried out on patients treated on an institutional review board (IRB)-approved protocol using ICBT for DES ISR between January 2011 and October 2016. All subjects were followed for 24 months for procedural complications, mortality, clinical ISR/target lesion revascularization (TLR) and stroke. A total of 290 patients were identified with a mean age of 66.6 years. All subjects had high rates of typical coronary artery disease (CAD) risk factors. The primary outcome, composite of in-hospital mortality, myocardial infarction (MI), safety outcomes and procedural failure was noted in 1 (0.3%) patient who had a MI. No other secondary outcome was noted in-hospital. At 1-year follow up, 12.4% patients had ISR, 1.7% patients died, and 1 (0.3%) had ischemic stroke. At 2-year, 14.7% had ISR, and a total 6 (2.1%) patients had MI. The authors concluded that ICBT demonstrates excellent technical success rates for treatment, safety, and reasonable efficacy over 2-years to be free from recurrent clinical ISR. This study represented the largest ICBT data for DES ISR to-date among very complex lesion subsets, however, more prospective data are still needed to determine the optimal patient for treatment.
Intravascular Lithotripsy for Peripheral Artery Calcification
Tepe et al., (2021) reported on short-term results of the Disrupt PAD III randomized trial, which evaluated whether intravascular lithotripsy (IVL) provides superior vessel preparation compared with standard percutaneous transluminal angioplasty (PTA) before drug‑coated balloon treatment or provisional stenting in patients with moderately or severely calcified femoropopliteal artery disease. The study enrolled 306 patients with symptomatic peripheral artery disease and heavy arterial calcification, randomly assigning them to IVL or PTA. After successful guidewire crossing of the target lesion, patients underwent the assigned vessel preparation technique, followed by drug‑coated balloon therapy or stenting when required. The primary endpoint, procedural success defined as ≤30% residual stenosis without flow‑limiting dissection, was assessed by an independent core laboratory prior to definitive treatment. IVL demonstrated higher procedural success (65.8% vs. 50.4%) and resulted in lower residual stenosis and fewer severe dissections compared with PTA. Patients treated with PTA required more post‑dilatation and had a markedly higher rate of provisional stenting (18.3% vs. 4.6%), suggesting that IVL more effectively modifies vessel compliance and reduces the need for additional interventions. Safety outcomes at 30 days were excellent in both groups, with very low major adverse event rates and no deaths, although two complications, one perforation and one distal embolization, occurred only in the PTA arm. Hemodynamic and functional improvements were similar between groups, though quality‑of‑life scores modestly favored IVL. Study limitations include its comparison of IVL only to PTA, leaving uncertainty about how IVL would perform relative to atherectomy or other calcium‑modifying devices. Interpretation of results is complicated by the fact that all patients ultimately received drug‑coated balloon therapy or stenting, making it difficult to attribute longer‑term outcomes solely to the vessel‑preparation strategy. The findings also may not generalize to patients with critical limb ischemia or infrapopliteal disease because of eligibility restrictions. Additionally, although core laboratories were blinded, treating clinicians were not, raising the possibility of procedural bias. Finally, only short‑term outcomes were reported in this study. Overall, the investigators found that IVL is an effective and safe method of vessel preparation that reduces procedural complications and the need for stenting in heavily calcified femoropopliteal arteries.
An accompanying commentary (White et al., 2021) noted that there was no difference in the angiographic result between the 2 groups. Final residual stenosis following DCB and/or stent placement was similar between the 2 groups (21.5 ± 7.8% with IVL vs. 20.7 ± 9.1% with PTA; p = 0.39). The use of IVL did not result in superior luminal gain, which we would have expected if these calcified lesions truly impaired balloon expansion. To achieve this parity, the PTA preparation group used higher balloon inflation pressures and more stents while inducing a higher rate of flow-limiting dissection (1.4% with IVL vs. 6.8% with PTA). The accompanying commentary noted that more than 1 in 10 (13%) angiographic images in the PTA group were not available for endpoint assessment, which suggests a problem in protocol compliance. The commentator stated that, "more seriously troubling is the dominant and asymmetrical use of BMS without DCBs in the PTA preparation group, driven by the unblinded operators’ preference. This will likely be problematic in a trial whose eventual outcome will measure 1-year patency and the device’s ultimate utility."
Tepe et al. (2022) reported mid-term results of the aforementioned Disrupt PAD III randomized controlled trial, which evaluated whether intravascular lithotripsy (IVL) offers superior vessel preparation and longer-term patency compared with percutaneous transluminal angioplasty (PTA) in patients with heavily calcified femoropopliteal peripheral artery disease. The study enrolled 306 symptomatic patients with moderate-to-severe arterial calcification who were randomized to IVL or PTA prior to treatment with a drug-coated balloon (DCB) or provisional stenting. IVL uses low-pressure acoustic shockwaves to fracture superficial and deep calcium, aiming to improve luminal compliance without causing the vessel trauma commonly associated with high-pressure PTA. The primary objective of this mid‑term analysis was to assess primary patency at 1 and 2 years, defined as freedom from clinically driven target lesion revascularization, restenosis, and provisional stenting. The study demonstrated that IVL resulted in significantly higher primary patency at both 1 year (80.5% vs 68.0%, P = .017) and 2 years (70.3% vs 51.3%, P = .003) compared with PTA, with differences primarily driven by IVL’s substantially reduced need for provisional stenting (4.6% vs 18.3%, P < .0001). Freedom from restenosis and clinically driven revascularization alone was similar between treatment groups at both time points, suggesting that the patency advantage stemmed largely from fewer flow‑limiting dissections and better initial vessel preparation with IVL. The multivariable analysis identified IVL treatment, older age (>75 years), and non-CTO lesions as independent predictors of successful primary patency at one year. Both groups showed meaningful clinical improvement in ankle‑brachial index, quality‑of‑life measures, and Rutherford class, and major adverse events were infrequent and similar between arms. The study’s limitations include its comparison only between IVL and PTA, leaving the relative performance of IVL versus other calcium‑modifying technologies, such as rotational or directional atherectomy, uncertain. Results may not generalize to patients with chronic limb‑threatening ischemia or infrapopliteal disease, as these populations were largely excluded. The PTA outcomes in this trial may not reflect real‑world results, where restenosis and reintervention rates tend to be higher. Additionally, the study did not directly evaluate whether IVL improves drug uptake from DCBs, nor did it assess calcium morphology in detail, as angiography offers limited resolution for characterizing superficial versus deep or concentric versus eccentric calcium. Despite these limitations, the authors concluded that the trial provides the strongest evidence to date that IVL offers a safer and more predictable vessel preparation strategy than PTA, with durable mid‑term patency and reduced reliance on stenting in patients with severely calcified femoropopliteal disease.
Lenchur and Frishman (2024) noted that in the last 10 years, IVL has emerged as a novel therapy for the treatment of vascular calcification. In coronary blood vessels, IVL modifies arterial calcium and enables PCI to be carried out safely and consistently, while in peripheral blood vessels, IVL can be used as a stand-alone therapy for treating calcified plaque in patients with peripheral artery disease (PAD). Due to the success of the Disrupt CAD and Disrupt PAD clinical trials, IVL is now FDA-approved in the U.S. for use in both patients with coronary artery disease (CAD) and PAD. The widespread adoption of IVL for PAD is likely to mirror the swift uptake observed in CAD. Although questions remain regarding IVL's high cost and performance compared directly to other technologies such as atherectomy, its ease of use, speed, and safety make its future extremely promising for treating complex, heavily calcified lesions in both peripheral and coronary vessels. The authors concluded that more studies are needed to determine in what clinical scenarios IVL should be considered as opposed to atherectomy and whether there are types of calcified lesions where IVL is best utilized (i.e., concentric vs. eccentric).
Chandra et al. (2025) reported the results of the Disrupt PAD BTK II study, a prospective, multicenter, single‑arm investigation evaluating the Shockwave Medical Peripheral Intravascular Lithotripsy (IVL) System for the treatment of moderate to severely calcified below‑the‑knee arterial disease. Its objective was to address the limited evidence base for managing heavily calcified infrapopliteal lesions, a population often excluded from prior trials, by assessing procedural success, early safety, and short‑term clinical outcomes. Methods included enrolling 250 patients across 38 U.S. and European sites, all of whom had Rutherford category 3–5 ischemia and at least one calcified lesion between the distal popliteal artery and ankle. An independent angiographic core laboratory adjudicated outcomes, and the primary endpoints were 30‑day major adverse limb events or postoperative death and procedural success defined as ≤50% residual stenosis without serious angiographic complications. A total of 305 lesions were treated. Results showed a high procedural success rate of 97.9%, with mean preprocedural stenosis reduced from 78% to 29% after IVL and 26% after adjunctive therapy. Serious angiographic complications were rare, with no deaths and a 0.8% rate of major adverse limb events at 30 days. Clinical improvements were also observed: nearly half of treated limbs improved in Rutherford category, Vascular QoL scores increased significantly, and of patients with baseline wounds, 69% demonstrated healing or improvement. Study limitations include its single‑arm design, which precludes direct comparison with alternative therapies, potential bias in patient‑reported outcomes due to lack of blinding, exclusion of Rutherford 6 patients, and inconsistencies between site‑reported and core‑lab‑verified calcium severity. Additionally, the study did not mandate intravascular imaging or include a wound core laboratory, limiting granularity of lesion characterization and wound adjudication. Overall, the investigators concluded that the short‑term findings support IVL as an effective and safe strategy for complex calcified BTK lesions, pending longer‑term follow‑up.
Polyzene-F Nanocoated Coronary Stent System
Cutlip et al. (2022) stated that the Cobra Polyzene F nanocoated coronary stent system (PzF-coated stent) showed favorable clinical outcomes at 9 months; however, late results have not been reported. In a prospective, non-randomized study, these researchers examined the late safety and effectiveness of the PzF-coated stent for the treatment of de-novo coronary artery lesions. Patients with de-novo coronary artery lesions meeting eligibility criteria were enrolled in this trial and followed for 5 years. The primary endpoint was cardiac death, MI, target vessel failure (TVF), or clinically driven target vessel revascularization (TVR) at 9 months. Secondary endpoints included MACE, cardiac death, MI, or clinically driven TLR, clinically driven TLR, and definite or probable stent thrombosis (ST) during the 5-year follow-up. Endpoints at 5 years were analyzed as cumulative incidence accounting for the competing risk of death. Of 296 enrolled patients, 290 (98%) were evaluable at 5 years. By 5 years, MACE had occurred in 61 (21.3%), cardiac death in 11 (4.2%), MI in 25 (8.6%), and TLR in 34 (12.0%) subjects. Between follow-up years 1 and 5, a 1st MACE occurred in 17 (6.2%), including 10 (4.0%) cardiac deaths, 4 (1.6%) MIs, and 7 (2.9%) TLR events. There were no definite or probable ST. The authors concluded that the PzF-coated stent showed continued safety and effectiveness through 5 years with low-to-very low incident rates of MACE, MI, TLR, and ST between 1 to 5 years following stent placement.
Bian et al. (2023) noted that a stent for patients with coronary heart disease (CHD) provides a requirement for long-term anti-platelet therapy because of the high possibility of the development of stent thrombosis. It was against this background that both Cobra and Catania PzF stents were designed to reduce the occurrence of ST. In a systematic review and single-arm meta-analysis, these investigators examined the safety and effectiveness of a PzF-nanocoated stent. The inclusion criteria entailed studies among patients with PzF-nanocoated coronary stents and reported target vessel failure (TVF) and ST as the outcomes, and the exclusion criteria entailed reported patients who could not receive the adjunctive medical therapies or without the necessary endpoints. Studies regarding PzF-nanocoated stents were searched in PubMed, Embase, and Web of Science and other sources. Because of the existence of few reports and a lack of comparison groups, a single-arm meta-analysis was carried out in R software (v3.6.2), using a random-effects model with the generic inverse variance method. After a heterogeneity test, assessment of evidence quality was performed by using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) software. A funnel plot Egger's test was carried out to examine publication bias, and a sensitivity analysis was carried out to determine the robustness of the overall effects. A total of 6 studies of 1,768 subjects were included. The primary endpoint that pooled the TVF rate was 8.9% (95% CI: 7.5% to 10.2%), which comprised the pooled cardiac death (CD) rate (1.5%, 95% CI: 0% to 3%), MI rate (2.7%, 95% CI: 0.4% to 5.1%), TVR (4.8%, 95% CI: 2.4% to 7.2%), or TLR (5.2%, 95% CI: 4.2% to 6.4%), while the secondary endpoint ST was 0.4% (95% CI: 0.1% to 0.9%). The funnel plots of TVF, CD, TVR, and TLR did not show any serious publication bias, and TVF, TVR, and TLR showed evidence of moderate quality in GRADE assessment. The sensitivity analysis showed that TVF, TLR, and ST exhibited good stability (I² = 26.9%, 16.4%, and 35.5%, respectively), while the other endpoints demonstrated moderate instability. The authors concluded that these findings showed that the PzF-nanocoated coronary stents of the Cobra and Catania systems exhibited good safety and effectiveness in clinical application; however, the sample size of patients included in the reports was relatively small, and this meta-analysis will be updated if more studies in this field are published in the future.
The authors stated that as the amount of included reports and the total objective size were relatively small in this single-arm meta-analysis, publication bias analysis and sensitivity analysis were performed, which yielded relatively robust results. Moreover, there was a relatively obvious heterogeneity in some outcome parameters, and subgroup analysis showed that the main heterogeneity derived from the studies of COBRA stents. The principal drawback of this study was the lack of comparison studies such as an RCT clinical trial design, and the publication bias analysis may produce more accurate results when more studies are included.
Saphenous Vein Graft Interventions
Harskamp et al. (2016) noted that PCI of saphenous vein grafts (SVG) poses a high-risk for distal coronary thrombo-embolic events. Glycoprotein IIb/IIIa inhibitors are frequently used in hope of reducing the impact of this, although the safety and effectiveness of these drugs to improve outcomes in this setting are under-studied. In this study, patients were included if they had prior coronary artery bypass surgery and subsequently underwent PCI of greater than or equal to 1 SVG graft at a Dutch academic center between 1997 and 2008. These patients were matched 1:1 based on peri-procedural use of abciximab using a propensity-score matching algorithm based on 17 variables. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between abciximab use and MACCE (the composite measure of mortality, myocardial infarction, stroke and repeat revascularization) at 30 days and up to 1 year. The composite of 30-day MACCE occurred in 18 patients (15.3%) in the abciximab group and 16 patients (13.6%) in the propensity matched control group (OR: 1.13, 95% CI: 0.57 to 2.21, p = 0.73). At 1-year follow-up, MACCE rates were also similar (32.5% versus 33.9%, HR: 0.97, 95% CI: 0.59 to 1.59). Major bleeding (BARC types 3a-c) was higher in the abciximab group (11.9% versus 4.2%, OR: 2.80, 95% CI: 1.01 to 7.77). Ischemic outcomes did not differ among patients with ACS. The authors concluded that the use of intravenous abciximab was not associated with improved clinical outcomes up to 1-year among patients undergoing SVG PCI, but was related to more bleeding.
Thromboembolic Complications during Aneurysm Coiling
Martínez-Perez and associates (2017) evaluated the safety and effectiveness of abciximab for the treatment of thromboembolic complications during aneurysm coiling and identified the associated risk factors. From an aneurysm coiling database, patients treated with intra-arterial abciximab after experiencing thrombotic complications during the coiling procedure were selected for analysis. Complications following the use of abciximab were categorized as hemorrhage, distal migration of the thrombus, and aneurysm re-canalization. A total of 14 coiling patients sustained a thromboembolic complication and were treated with intra-arterial infusion of abciximab, leading to further analysis. The age range of the patients was 48 to 76 years; 3 patients were male, and 7 had subarachnoid hemorrhage. Only complete re-canalization was associated with clinical improvement, which occurred in just 4 (28.5%) cases. Partial or complete re-canalization was achieved in 13 (93%) patients; however, 8 (57%) experienced complications related to the infusion. Specifically, 3 had aneurysm re-canalization, 3 had distal migration of the thrombus, and 1 had a hemorrhagic complication. Additionally, 8 cases demonstrated acute infarcts related to the occluded vessel, while 7 patients made a good functional recovery. The authors concluded that successful re-canalization of a vessel occluded by thrombus formation during aneurysm coiling using abciximab infusion was less than optimal, with risks associated with abciximab, including bleeding and aneurysm re-canalization.
Lin and colleagues (2018) stated that flow diversion with the Pipeline embolization device (PED) is an effective neuro-endovascular method that is increasingly accepted for the treatment of cerebral aneurysms. Acute in-situ thrombosis is a known complication of PED procedures, and there is limited experience in the flow diversion literature regarding the use of abciximab for managing acute thrombus formation in PED cases. In a retrospective study, data were collected on patients who received intra-arterial (IA) ReoPro with or without subsequent intravenous (IV) infusion during PED flow diversion treatment of intracranial aneurysms. A total of 30 cases were identified, with a mean patient age of 56.7 years (range of 36 to 84) and a mean aneurysm size of 8.6 mm (range of 2 to 25), all of whom experienced intra-procedural thromboembolic complications during PED treatment. IA ReoPro was administered in all cases, with 20 cases receiving increments of 5-mg boluses and 10 cases receiving a 0.125 mg/kg IA bolus (half cardiac dosing). Complete or partial re-canalization was achieved in 100% of the cases. Post-procedurally, IV ReoPro infusion at 0.125 μg/kg/min for 12 hours was administered in 22 cases with residual thrombus. After the procedure, 18 patients were transitioned from clopidogrel (Plavix) to prasugrel (Effient). The majority of cases (23/30; 77%) were discharged home. Peri-procedural intracranial hemorrhage was noted in 2 cases (7%), and radiographic infarcts were noted in 4 cases (13%), with an overall mortality rate of 0% at the time of initial discharge. Clinical follow-up was available for 28/30 patients, with an average follow-up duration of 11.7 months, at which time 23/28 (82%) of the patients had a modified Rankin Scale (mRS) score of 0. The authors concluded that IA ReoPro administration was a safe and effective rescue strategy for managing acute intra-procedural thromboembolic complications during PED treatment. They suggested that using a dosing strategy of either 5-mg increments or a 0.125 mg/kg IA bolus (half cardiac dosing) could provide high rates of re-canalization with low rates of hemorrhagic complications and long-term morbidity.
The authors acknowledged that the drawbacks of this study were due to its retrospective, single-institution nature. Furthermore, there was heterogeneity in ReoPro dosing within this series. They stated that prospective, randomized trials are needed to establish further protocols.
References
The above policy is based on the following references:
- Adams HP Jr, Effron MB, Torner J, et al. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: Results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke. 2008;39(1):87-99.
- Ahmed JM, Mintz GS, Waksman R, et al. Serial intravascular ultrasound analysis of the impact of lesion length on the efficacy of intracoronary gamma-irradiation for preventing recurrent in-stent restenosis. Circulation. 2001;103(2):188-191.
- Ahrens I, Peter K, Bode C. Use of GPIIb/IIIa inhibitors in cardiovascular medicine. Expert Rev Cardiovasc Ther. 2003;1(2):233-242.
- Aksoy A, Tiyerili V, Jansen N, et al. Propensity-score-matched comparison of safety, efficacy, and outcome of intravascular lithotripsy versus high-pressure PTCA in coronary calcified lesions. Int J Cardiol Heart Vasc. 2021;37:100900.
- Alberta Heritage Foundation for Medical Research (AHFMR). Intracoronary brachytherapy for the treatment of in-stent restenosis. TechNote. TN 36. Edmonton, AB: AHFMR; May 2002.
- Albiero R, Adamian M, Kobayashi N, et al. Short- and intermediate-term results of (32)P radioactive beta-emitting stent implantation in patients with coronary artery disease: The Milan Dose-Response Study. Circulation. 2000;101(1):18-26.
- Albiero R, Nishida T, Adamian M, et al. Edge restenosis after implantation of high activity (32)P radioactive beta-emitting stents. Circulation. 2000;101(21):2454-2457.
- Al-Mufti F, Amuluru K, Manning NW, et al. Emergent carotid stenting and intra-arterial abciximab in acute ischemic stroke due to tandem occlusion. Br J Neurosurg. 2017:1-7.
- Ansel GM, Silver MJ, Botti CF, et al. Functional and clinical outcomes of nitinol stenting with and without abciximab for complex superficial femoral artery disease: A randomized trial. Catheter Cardiovasc Interv. 2006;67(2):288-297.
- Bachlava E, Loukopoulou S, Karanasios E, et al. Management of coronary artery aneurysms using abciximab in children with Kawasaki disease. Int J Cardiol. 2016;220:65-69.
- Badrawy Khalefa B, Elettreby AM, Arnaout M, et al. Intravascular lithotripsy versus rotational atherectomy in calcified coronary artery disease: A systematic review and meta-analysis. Coron Artery Dis. 2026 January 13 [Online ahead of print].
- Barbato E, Gallinoro E, Abdel-Wahab M, et al. Management strategies for heavily calcified coronary stenoses: An EAPCI clinical consensus statement in collaboration with the EURO4C-PCR group. Eur Heart J. 2023;44(41):4340-4356.
- Bertrand OF, Rodés-Cabau J, Larose E, et al. Effects of intracoronary compared to intravenous abciximab administration in patients undergoing transradial percutaneous coronary intervention: A sub-analysis of the EASY trial. Int J Cardiol. 2009;136(2):165-170.
- Bian J, Yang R, Wang D, et al. Evaluation of the safety and efficacy of a Polyzene-F nanocoated coronary stent system: A systematic review and single-arm meta-analysis. Front Cardiovasc Med. 2023;10:1095794.
- BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Intracoronary brachytherapy as an adjunct to percutaneous revascularization to prevent and manage restenosis. TEC Assessment Program. Chicago IL: BCBSA; August 2002;17(9).
- Braunwald E, Antman EM, Beasley JW, et al. American College of Cardiology; American Heart Association. Committee on the Management of Patients With Unstable Angina. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction--summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002;40(7):1366-1374.
- Brown A, Mittmann N, Seung SJ, et al. Economic evaluation of glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention with stenting. Technology Report No. 54. Ottawa, ON: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); March 2005:1-78.
- Buchanan IA, Lee B, Amar AP, Giannotta SL. In situ administration of abciximab for thrombus resolution during intracranial bypass surgery: Case report. J Neurosurg. 2018;130(1):268-272.
- Butala NM, Waldo SW, Secemsky EA, et al. Use of calcium modification during percutaneous coronary intervention after introduction of coronary intravascular lithotripsy. JSCAI. 2024;3(2):101254.
- Caldeira D, Pereira H, Marques A, et al; investigators of the Portuguese Registry of Acute Coronary Syndromes (ProACS), investigators of the Portuguese Registry on Interventional Cardiology (PRIC). Adjuvant antithrombotic therapy in ST-elevation myocardial infarction: Contemporaneous Portuguese cross-sectional data. Rev Port Cardiol. 2019;38(11):809-814.
- Caminiti R, Vetta G, Parlavecchio A, et al. A systematic review and meta-analysis including 354 patients from 13 studies of intravascular lithotripsy for the treatment of underexpanded coronary stents. Am J Cardiol. 2023;205:223-230.
- Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Glycoprotein IIb/IIIa antagonists: A systematic review of randomized clinical trials in patients undergoing percutaneous coronary intervention. Technology Report No. 49. Ottawa, ON: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); January 2005:1-72.
- Castagna MT, Mintz GS, Weissman NJ, et al. Intravascular ultrasound analysis of the impact of gamma radiation therapy on the treatment of saphenous vein graft in-stent restenosis. Am J Cardiol. 2002;90(12):1378-1381.
- Centocor. REOPRO® (abciximab) [website]. Leiden, The Netherlands; Centocor; 2006. Available at: http://www.centocor.nl/producten/default.aspx?rID=4. Accessed January 20, 2006.
- Cerrato E, Pavani M, Zecchino S, et al. Intravascular lithotripsy or mechanical debulking in complex calcified coronary arteries: Multicenter, prospective ROLLING STONE Study. JACC Cardiovasc Interv. 2026 January 24 [online ahead of print].
- Chandra V, Lansky AJ, Sayfo S, et al. Thirty-day outcomes from the Disrupt PAD BTK II study of the Shockwave Intravascular Lithotripsy System for treatment of
calcified below-the-knee peripheral arterial disease. J Vasc Surg. 2025;81(3):710-719. - Chougule PB. Vascular radiation therapy to reduce coronary artery restenosis. Surg Oncol Clin N Am. 2000;9(3):577-584.
- Ciccone A, Abraha I, Santilli I. Glycoprotein IIb-IIIa inhibitors for acute ischaemic stroke. Cochrane Database Syst Rev. 2006;(4):CD005208.
- Comite d'Evaluation et de Diffusion des Innovations Technologiques (CEDIT). Intracoronary brachytherapy - systematic review, expert panel. Paris, France: CEDIT; 2001.
- Conseil d'Evaluation des Technologies de la Sante du Quebec (CETS). The use of abciximab (c7E3 Fab) as a therapeutic adjunct to transluminal coronary balloon angioplasty - systematic review. Montreal, QC: CETS; 1998:1-18.
- Crocker I. Radiation therapy to prevent coronary artery restenosis. Semin Radiat Oncol. 1999;9(2):134-143.
- Cutlip D. Specialized revascularization devices in the management of coronary heart disease. UpToDate [online serial], Waltham, MA: UpToDate; reviewed March 2025.
- Cutlip DE, Jauhar R, Meraj P, et al. Five-year clinical outcomes of the COBRA Polyzene F nanocoated coronary stent system. Cardiovasc Revasc Med. 2022;41:76-80.
- De Luca G, Verdoia M, Suryapranata H. Benefits from intracoronary as compared to intravenous abciximab administration for STEMI patients undergoing primary angioplasty: A meta-analysis of 8 randomized trials. Atherosclerosis. 2012;222(2):426-433.
- De Rosa S, Caiazzo G, Torella D, Indolfi C. Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: A meta-analysis of clinical trials. Int J Cardiol. 2013;168(2):1298-1305.
- Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P, et al. Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention -- effects on soluble CD40 ligand concentrations. Atherosclerosis. 2009;206(2):523-527.
- Dong L, Zhang F, Shu X. Upstream vs deferred administration of small-molecule glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Insights from randomized clinical trials. Circ J. 2010;74(8):1617-1624.
- Eitel I, Wohrle J, Suenkel H, et al. Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: Cardiac magnetic resonance substudy of the AIDA STEMI Trial. J Am Coll Cardiol. 2013;61(13):1447-1454.
- Fan P, Chiu-Tsao ST, Patel NS, et al. Effect of stent on radiation dosimetry in an in-stent restenosis model. Cardiovasc Radiat Med. 2000;2(1):18-25.
- Farhat H, Kuzemczak M, Durel N, et al. Rotational atherectomy versus intravascular lithotripsy for calcified in-stent restenosis: A single-center study with 1-year follow-up. Am J Cardiol. 2023:205:413-419.
- Fischell TA, Hehrlein C. The radioisotope stent for the prevention of restenosis. Herz. 1998;23(6):373-379.
- Fischell TA. Radioactive stents. Semin Interv Cardiol. 1998;3(2):51-56.
- Gardiner R, Muradagha H, Kiernan TJ. Intravascular lithotripsy during percutaneous coronary intervention: Current concepts. Expert Rev Cardiovasc Ther. 2022;20(4):323-338.
- Ghaffari S, Kereiakes DJ, Lincoff AM, et al. Platelet glycoprotein IIb/IIIa receptor blockade with abciximab reduces ischemic complications in patients undergoing directional coronary atherectomy. EPILOG Investigators. Evaluation of PTCA to Improve Long-term Outcome by c7E3 GP IIb/IIIa Receptor Blockade. Am J Cardiol. 1998;82(1):7-12.
- Gurm HS, Tamhane U, Meier P, et al. A comparison of abciximab and small-molecule glycoprotein IIb/IIIa inhibitors in patients undergoing primary percutaneous coronary intervention: A meta-analysis of contemporary randomized controlled trials. Circ Cardiovasc Interv. 2009;2(3):230-236.
- Hang CL, Hsieh BT, Wu CJ, et al. Six-year clinical follow-up after treatment of diffuse in-stent restenosis with cutting balloon angioplasty followed by intracoronary brachytherapy with liquid rhenium-188-filled balloon via transradial approach. Circ J. 2010;75(1):113-120.
- Harskamp RE, Hoedemaker N, Newby LK, et al. Procedural and clinical outcomes after use of the glycoprotein IIb/IIIa inhibitor abciximab for saphenous vein graft interventions. Cardiovasc Revasc Med. 2016;17(1):19-23.
- Hehrlein C, Kubler W. Advantages and limitations of radioactive stents. Semin Interv Cardiol. 1997;2(2):109-113.
- Hesse K, Shahid F, Ahmed R, et al. Early experience of intravascular lithotripsy in unprotected calcified left main coronary artery disease. Cardiovasc Revasc Med. 2023;55:33-41.
- Hill JM, KereiakesDJ, Shlofmitz RA, et al. Intravascular lithotripsy for treatment of severely calcified coronary artery disease. J Am Coll Cardiol. 2020;76(22):2635-2646.
- Honton B, Monsegu J. Best practice in intravascular lithotripsy. Interv Cardiol. 2022;17:e02.
- Howard K, Barr E. Intravascular brachytherapy. Assessment Report. MSAC Application 1041. Canberra, ACT; Medical Services Advisory Committee (MSAC); August 2002.
- Institute for Clinical Systems Improvement. Intracoronary brachytherapy to treat restenosis after stent placement (in-stent restenosis). Technology Assessment Report No. 63. Bloomington, MN: ICSI; May 2002.
- Jattari HE, Holvoet W, De Roeck F, et al. Intracoronary lithotripsy in calcified coronary lesions: A multicenter observational sStudy. J Invasive Cardiol. 2022;34(1):E24-E31.
- Kaluza GL, Raizner AE. Brachytherapy for restenosis after stenting for coronary artery disease: Its role in the drug-eluting stent era. Curr Opin Cardiol. 2004;19(6):601-607.
- Karathanos A, Lin Y, Dannenberg L, et al. Routine glycoprotein IIb/IIIa inhibitor therapy in ST-segment elevation myocardial infarction: A meta-analysis. Can J Cardiol. 2019;35(11):1576-1588.
- Kay IP, Sabate M, Van Langenhove G, et al. Outcome from balloon induced coronary artery dissection after intracoronary beta radiation. Heart. 2000;83(3):332-337.
- Kereiakes DJ, Di Mario C, Riley RF, et al. Intravascular lithotripsy for treatment of calcified coronary lesions: Patient-level pooled analysis of the disrupt CAD studies. JACC Cardiovasc Interv. 2021;14(12):1337-1348.
- Kereiakes DJ, Hill JM, Ben-Yehuda O, et al. Evaluation of safety and efficacy of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses: Design and rationale for the Disrupt CAD III trial. Am Heart J. 2020;225:10-18.
- Kereiakes DJ, Hill JM, Shlofmitz RA, et al; on behalf of the Disrupt CAD III Investigators. Intravascular lithotripsy for treatment of severely calcified coronary lesions: 1-year results from the Disrupt CAD III Study. J Soc Cardiovasc Angiogr Interv. 2022;1(1).
- Kereiakes DJ, Hill JM, Shlofmitz RA, et al; Disrupt CAD III Investigators. Intravascular lithotripsy for treatment of severely calcified coronary arteries: 2-year results -- Disrupt CAD III Study. JACC Cardiovasc Interv. 2023;16(19):2472-2474.
- King SB, Williams DO, Chougule P, et al. Endovascular beta-radiation to reduce restenosis after coronary balloon angioplasty: Results of the beta energy restenosis trial (BERT). Circulation. 1998;97(20):2025-2030.
- Kong DF, Hasselblad V, Harrington RA, et al. Meta-analysis of survival with platelet glycoprotein IIb/IIIa antagonists for percutaneous coronary interventions. Am J Cardiol. 2003;92(6):651-655.
- Kristensen AT, Christiansen EH, Holm NR, et al. Balloon lithotripsy added to conventional preparation before stent implantation in severely calcified coronary lesions. JACC Cardiovasc Interv. 2026;19(3):331-341.
- Kumar S, Rajshekher G, Prabhakar S. Platelet glycoprotein IIb/IIIa inhibitors in acute ischemic stroke. Neurol India. 2008;56(4):399-404.
- Labinaz M, Ho C, Banerjee S, et al. Meta-analysis of clinical efficacy and bleeding risk with intravenous glycoprotein IIb/IIIa antagonists for percutaneous coronary intervention. Can J Cardiol. 2007;23(12):963-970.
- Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145:e18-e114.
- Lee CH, Ngo HM, Sewianto A, et al. Comparison between fixed-dose, intracoronary bolus-only versus standard weight-adjusted dose, intravenous bolus and infusion administration of abciximab in patients undergoing primary percutaneous coronary intervention. Int J Cardiol. 2010;145(2):355-357.
- Lee CL, Colombo PC, Eisenberger A, et al. Abciximab/heparin therapy for left ventricular assist device implantation in patients with heparin-induced thrombocytopenia. Ann Thorac Surg. 2018;105(1):122-128.
- Lenchur PD, Frishman WH. A novel approach to calcium destruction in coronary and peripheral blood vessels: Intravascular lithotripsy. Cardiol Rev. 2024;32(6):566-571.
- Leon MB, Teirstein PS, Moses JW, et al. Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting. N Engl J Med. 2001;344:250-256.
- Li AN, Eigler NL, Litvack F, et al. Characterization of a positron emitting V48 nitinol stent for intracoronary brachytherapy. Med Phys. 1998;25(1):20-28.
- Lim VY, Chan CN. Prevention of restenosis after percutaneous coronary intervention: The continuing challenge. Ann Acad Med Singapore. 2002;31(1):102-106.
- Liang B, Gu N. Evaluation of the safety and efficacy of coronary intravascular lithotripsy for treatment of severely calcified coronary stenoses: Evidence from the serial Disrupt CAD Trials. Front Cardiovasc Med. 2021;8:724481.
- Lin LM, Jiang B, Campos JK, et al. Abciximab (ReoPro) dosing strategy for the management of acute intraprocedural thromboembolic complications during Pipeline flow diversion treatment of intracranial aneurysms. Interv Neurol. 2018;7(5):218-232.
- Lincoff AM, Tcheng JE, Califf RM, et al. Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial.Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Circulation. 1999;99(15):1951-1958.
- Lv H, Li X, Ren Z, et al. Intravascular lithotripsy: A novel option for severe calcification of coronary artery. Clin Cardiol. 2024;47(2):e24186.
- Mangione FM, Jatene T, Badr Eslam R, et al. Usefulness of intracoronary brachytherapy for patients with resistant drug-eluting stent restenosis. Am J Cardiol. 2017;120(3):369-373.
- Martínez-Perez R, Lownie SP, Pelz DM. Intra-arterial use of abciximab in thromboembolic complications associated with cerebral aneurysm coiling: The London Ontario experience. World Neurosurg. 2017;100:342-350.
- McEntegart M, Gonzalo N, Fendelander L, et al. Equity in modifying plaque of women with undertreated calcified coronary artery disease: Design and rationale of EMPOWER CAD study. J Soc Cardiovasc Angiogr Interv. 2024;3(11):102289.
- McEntegart M, Gonzalo N, Shlofmitz R, et al. Treating women with calcified coronary arteries using intravascular lithotripsy: Primary results of the EMPOWER CAD study. J Soc Cardiovasc Angiogr Interv. 2026 [online ahead of print].
- Meijer M, Oliveri F, van Oort MJH, et al. Intravascular lithotripsy for the treatment of peri-stent calcific lesions in saphenous vein grafts: A case series report Cardiovasc Revasc Med. 2025;70:85-91.
- Meraj PM, Patel K, Patel A, et al. Northwell intracoronary brachytherapy for the treatment of recurrent drug eluting stent in-stent restenosis (NITDI Study Group). Catheter Cardiovasc Interv. 2021;97(1):41-46.
- Mhanna M, Beran A, Nazir S, et al. Efficacy and safety of intravascular lithotripsy in calcified coronary lesions: A systematic review and meta-analysis. Cardiovasc Revasc Med. 2022;36:73-82.
- Moghadam AS, Kakavand N, Shirmard FO, et al. Intravascular lithotripsy versus rotational atherectomy in the management of calcific coronary lesions: A systematic review and meta-analysis. Catheter Cardiovasc Interv. 2025;106(2):1142-1152.
- Mukherjee D, Reginelli JP, Moliterno DJ, et al. Unexpected mortality reduction with abciximab for in-stent restenosis. J Invasive Cardiol. 2000;12(11):540-544.
- Nair SV, McEwan JR. Angina pectoris: Interventional therapies and treatment of restenosis. Int J Biochem Cell Biol. 2003;35(10):1399-1406.
- Nakahama H, Jankowski M, Dixon SR, Abbas AE. Long-term outcome of brachytherapy treatment for coronary in-stent restenosis: Ten-year follow-up. Catheter Cardiovasc Interv. 2019;93(4):E211-E216.
- National Horizon Scanning Centre (NHSC). Abciximab (Reopro) for acute ischemic stroke - horizon scanning review. Birmingham, UK: NHSC; 2005.
- National Horizon Scanning Centre (NHSC). Preventing restenosis after PTCA. Birmingham, UK: NHSC; 2001.
- National Institute for Clinical Excellence (NICE). Guidance on the use of glycoprotein IIb/IIIa inhibitors in the treatment of acute coronary syndromes. Technology Appraisal No. 47. London, UK: NICE; September 2002:1-24.
- No authors listed. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet. 1997;349(9063):1429-1435.
- No authors listed. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. The EPIC Investigation. N Engl J Med. 1994;330(14):956-961.
- Novoste Corporation. Novoste announces results of BETA-CATH system trial; beta radiation shown to reduce in-lesion restenosis in balloon angioplasty patients in largest ever trial of vascular brachytherapy. Press Resease. Norcross, GA: Noveste; 2001.
- Oksnes A, Cosgrove C, Walsh S, et al. Intravascular lithotripsy for calcium modification in chronic total occlusion percutaneous coronary intervention. J Interv Cardiol. 2021;2021:9958035.
- Oliver LN, Buttner PG, Hobson H, Golledge J. A meta-analysis of randomised controlled trials assessing drug-eluting stents and vascular brachytherapy in the treatment of coronary artery in-stent restenosis. Int J Cardiol. 2008;126(2):216-223.
- Oliveri F, van Oort MJH, Al Amri I, et al. Intravascular lithotripsy in acute coronary syndromes: Procedural and one-year clinical outcomes from the BENELUX-IVL registry. Catheter Cardiovasc Interv. 2025b;105(2):385-393.
- Oliveri F, van Oort MJH, Phagu AAS, et al. Intravascular lithotripsy in calcified left main coronary artery: Procedural success and 1-year clinical outcomes. Int J Cardiol. 2025a;423:132996.
- Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Intracoronary radiation therapy. Health Technology Scientific Literature Review. Toronto, ON: Ontario Ministry of Health and Long-Term Care; December 2001.
- Prati F, Romagnoli E, Limbruno U, et al. Randomized evaluation of intralesion versus intracoronary abciximab and aspiration thrombectomy in patients with ST-elevation myocardial infarction: The COCTAIL II trial. Am Heart J. 2015;170(6):1116-1123.
- Quast U, Fluhs D, Bambynek M. Endovascular brachytherapy--treatment planning and radiation protection. Herz. 1998;23(6):337-346.
- Radhoe SP, Schuurman A-S, Ligthart JM, et al. Two decades after coronary radiation therapy: A single center longitudinal clinical study. Catheter Cardiovasc Interv. 2020;96(3):E204-E212.
- Rao RS, Sharma GN, Kunal S, et al. Safety and procedural outcomes of intravascular lithotripsy in calcified coronaries in Indian patients. Indian Heart J. 2022;74(2):91-95.
- Rawal S, Sawant AC, Sridhar M, et al. Impact of intravascular brachytherapy on patient-reported outcomes in patients with coronary artery disease. Cardiovasc Revasc Med. 2020;21(12):1550-1554.
- Rezkalla, SH, Benz M. Antiplatelet therapy from clinical trials to clinical practice. Clin Med Res. 2003; 1(2): 101-104.
- Riley RF, Patel MP, Abbott JD, et al. SCAI expert consensus statement on the management of calcified coronary lesions. J. Soc. Cardiovasc. Angiogr. Interv. 2024;3:101259.
- Robinson M, Ginnelly L, Sculpher M, et al. A systematic review update of the clinical effectiveness and cost-effectiveness of glycoprotein IIb/IIIa antagonists. Health Technology Assess. 2002;6(25):1-160.
- Rodriguez-Leor O, Cid-Alvarez AB, Lopez-Benito M, et al; REPLICA-EPIC18 Investigators. A prospective, multicenter, real-world registry of coronary lithotripsy in calcified coronary arteries: The REPLICA-EPIC18 Study. JACC Cardiovasc Interv. 2024;17(6):756-767.
- Rola P, Kulczycki JJ, Włodarczak A, et al. Intravascular lithotripsy as a novel treatment method for calcified unprotected left main diseases -- Comparison to rotational atherectomy -- Short-term outcomes. Int J Environ Res Public Health. 2022;19(15): 9011.
- Rola P, Wlodarczak A, Barycki M, et al. Shockwave intravascular lithotripsy as a novel strategy for balloon undilatable heavily calcified chronic total occlusion lesions. Cardiol J. 2023;30(5):677-684.
- Sagris M, Ktenopoulos N, Dimitriadis K, et al. Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis. Catheter Cardiovasc Interv. 2024;103(5):710-721.
- Salzler GG, Graham A, Connolly PH, et al. Safety and effectiveness of adjunctive intra-arterial abciximab in the management of acute limb ischemia. Ann Vasc Surg. 2016;30:66-71.
- Sandesara PB, Hassan ME, Shekiladze N, et al. Intravascular lithotripsy compared to rotational atherectomy for the treatment of calcified distal left main coronary artery disease: A single center experience. Catheter Cardiovasc Interv. 2023;102(6):997-1003.
- Sapirstein W, Zuckerman B, Dillard J. FDA approval of coronary-artery brachytherapy. N Engl J Med. 2001;344(4):297-299.
- Sattar Y, Almas T, Arshad J, et al. Clinical and angiographic success and safety comparison of coronary intravascular lithotripsy: An updated meta-analysis. Int J Cardiol Heart Vasc. 2022;39:100975.
- Schalcher C, Sutsch G, Amann FW. To stent or not to stent. Schweiz Med Wochenschr. 1999;129(45):1679-1696.
- Schulz S, Birkmeier KA, Ndrepepa G, et al. One-year clinical outcomes with abciximab in acute myocardial infarction: Results of the BRAVE-3 randomized trial. Clin Res Cardiol. 2010;99(12):795-802.
- Seitz RJ, Siebler M. Platelet GPIIb/IIIa receptor antagonists in human ischemic brain disease. Curr Vasc Pharmacol. 2008;6(1):29-36.
- Sharma SK. Shock wave intravascular lithotripsy (IVL)-assisted staged percutaneous coronary Intervention (PCI) for a calcified right coronary artery in a patient with unstable angina: Shock the rock. Cureus. 2022;14(4):e24489.
- Sheppard R, Eisenberg MJ, Donath D, Meerkin D. Intracoronary brachytherapy for the prevention of restenosis after percutaneous coronary revascularization. Am Heart J. 2003;146(5):775-786.
- State of Minnesota, Health Technology Advisory Committee (HTAC). Intracoronary brachytherapy. St. Paul, MN: HTAC; 2001.
- Stone GW, Maehara A, Witzenbichler B, et al; for the INFUSE-AMI Investigators. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: The INFUSE-AMI Randomized Trial. JAMA. 2012;307(17):1817-1826.
- Suruagy-Motta RFO, Cabeça LS, Da Silva AMP, et al. Intravascular lithotripsy versus rotational atherectomy for calcified coronary lesions: A systematic review and an updated meta-analysis of clinical outcomes. Catheter Cardiovasc Interv. 2025;106(1):563-572.
- Swedish Council on Technology Assessment in Health Care (SBU). Abciximab (ReoPro) in coronary artery disease - early assessment briefs (ALERT). Stockholm, Sweden: Swedish Council on Technology Assessment in Health Care (SBU); 2001.
- Tamhane UU, Gurm HS. The chimeric monoclonal antibody abciximab: A systematic review of its safety in contemporary practice. Expert Opin Drug Saf. 2008;7(6):809-819.
- Teirstein PS, Massullo V, Jani S, et al. Three-year clinical and angiographic follow-up after intracoronary radiation: Results of a randomized clinical trial. Circulation. 2000;101:360-365.
- Tepe G, Brodmann M, Bachinsky W, et al; Disrupt PAD III Investigators. Intravascular lithotripsy for peripheral artery calcification: Mid-term outcomes from the randomized Disrupt PAD III trial. J Soc Cardiovasc Angiogr Interv. 2022;1:100341.
- Tepe G, Brodmann M, Werner M, et al.; Disrupt PAD III Investigators. Intravascular lithotripsy for peripheral artery calcification: 30-day outcomes from the randomized Disrupt PAD III Trial. JACC Cardiovasc Interv. 2021;14(12):1352-1361.
- The Norwegian Knowledge Centre for the Health Services. Prevention of restenosis. Oslo, Norway: The Norwegian Knowledge Centre for the Health Services; 2004.
- Thiele H, Wohrle J, Hambrecht R, et al. Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: A randomised trial. Lancet. 2012;379(9819):923-31.
- Tripuraneni P. Coronary artery radiation therapy for the prevention of restenosis after percutaneous coronary angioplasty, II: Outcomes of clinical trials. Semin Radiat Oncol. 2002;12(1):17-23.
- Umapathy S, Keh YS, Wong N, et al. Real-world experience of coronary intravascular lithotripsy in an Asian population: A retrospective, observational, single-center, all-comers registry. J Invasive Cardiol. 2021;33(6):E417-E424.
- U.S. Food and Drug Administration (FDA), Center for Devices and Radiological Health. Premarket approval of Cordis Checkmate System. Rockville, MD: FDA; November 2000.
- U.S. Food and Drug Administration (FDA), Center for Devices and Radiological Health. Premarket approval of Novoste Beta-Cath System. Rockville, MD: FDA; November 2000.
- U.S. Food and Drug Administration (FDA). ReoPro Abciximab for intravenous administration. Prescribing Information. Rockville, MD: FDA; 1997.
- Verin V, Popowski Y, de Bruyne B, et al. Endoluminal beta-radiation therapy for the prevention of coronary restenosis after balloon angioplasty. N Engl J Med. 2001;344:243-249.
- Waksman R, Ajani AE, White RL, et al. Intravascular gamma radiation for in-stent restenosis in saphenous-vein bypass grafts. N Engl J Med. 2002;346(16):1194-1199.
- Waksman R, White RL, Chan RC, et al. Intracoronary gamma-radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis. Circulation. 2000;101(18):2165-2171.
- Wang JN, Diao S, Tang YJ, et al. Intracoronary versus intravenous administration of abciximab in patients with acute coronary syndrome: A meta-analysis. PLoS One. 2013;8(2):e58077.
- Wardeh AJ, Kay IP, Sabate M, et al. Beta-particle-emitting radioactive stent implantation. A safety and feasibility study. Circulation. 1999;100(16):1684-1689.
- Weinberger J, Simon AD. Intracoronary irradiation for the prevention of restenosis. Curr Opin Cardiol. 1997;12(5):468-474.
- White CJ, Beckman JA. Making lemonade out of the lemons of lesion preparation. JACC Cardiovasc Interv. 2021;14(12):1362-1363.
- Yap LB, Choy CN, Navin S, et al. Intravascular imaging-guided treatment of severe coronary artery calcification with orbital atherectomy: A prospective single-centre registry. Med J Malaysia. 2023;78(1):7-13.
- Yap LB, Choy CN, Navin S, et al. Treatment of severe coronary artery calcification with intravascular lithotripsy: Initial experience of a prospective single centre registry. Med J Malaysia. 2022;77(4):500-505.
