Abdominal Aortic Aneurysm Screening

Number: 0702

Policy

Aetna considers one-time ultrasound screening for abdominal aortic aneurysms (AAA) medically necessary for men 65 years of age or older.

Aetna considers AAA screening experimental and investigational for all other indications because its effectiveness for indications other than the one listed above has not been established.

Background

The U.S. Preventive Services Task Force (USPSTF) recommends one-time screening for abdominal aortic aneurysm (AAA) by ultrasonography in men aged 65 to 75 who have ever smoked.  This recommendation was based on the results of published randomized controlled clinical studies of screening for abdominal aortic aneurysms (Scott et al, 1995; Vardulaki et al, 2002; Scott et al, 2002; Lindholt et al, 2002; Ashton et al, 2002; Norman et al, 2003).

The USPSTF found good evidence that screening for AAA and surgical repair of large AAAs (5.5 cm or more) in men aged 65 to 75 who have ever smoked (current and former smokers) leads to decreased AAA-specific mortality.  The USPSTF found that there is good evidence that abdominal ultrasonography, performed in a setting with adequate quality assurance (i.e., in an accredited facility with credentialed technologists), is an accurate screening test for AAA.  The USPSTF also identified, however, important harms of screening and early treatment, including an increased number of surgeries with associated clinically-significant morbidity and mortality, and short-term psychological harms.  Based on the moderate magnitude of net benefit, the USPSTF concluded that the benefits of screening for AAA in men aged 65 to 75 who have ever smoked outweigh the harms.

The USPSTF made no recommendation for or against screening for AAA in men aged 65 to 75 who have never smoked.  Although the USPSTF found good evidence that screening for AAA in men aged 65 to 75 who have never smoked leads to decreased AAA-specific mortality, there is a lower prevalence of large AAAs in men who have never smoked compared with men who have ever smoked; thus, the USPSTF determined that the potential benefit from screening men who have never smoked is small.  The USPSTF also weighed the harms of screening and early treatment, and concluded that the balance between the benefits and harms of screening for AAA is too close to make a general recommendation in this population.

The USPSTF recommended against routine screening for AAA in women.  The USPSTF explained that, because of the low prevalence of large AAAs in women, the number of AAA-related deaths that can be prevented by screening this population is small.  The USPSTF concluded that the harms of screening women for AAA outweigh the benefits.

The USPSTF reported that one-time screening to detect an AAA using ultrasonography is sufficient.  They concluded that there is negligible health benefit in re-screening those who have normal aortic diameter on initial screening.  The USPSTF concluded that, for most men, 75 years may be considered an upper age limit for screening.  Patients can not benefit from screening and subsequent surgery unless they have a reasonable life expectancy.  The USPSTF explained that increased presence of co-morbidities for people aged 75 and older decreases the likelihood that they will benefit from screening.

It is generally recommended that patients with AAA of 5.5 cm or greater seek open surgical repair.  Open surgical repair for an AAA of at least 5.5 cm leads to an estimated 43 % reduction in AAA-specific mortality in older men who undergo screening.  However, there is no current evidence that screening reduces all-cause mortality in this population.

The USPSTF reported that, in men with intermediate-sized AAAs (4.0 to 5.4 cm), periodic surveillance offers comparable mortality benefit to routine elective surgery with the benefit of fewer operations.  The USPSTF found no evidence to support the effectiveness of any intervention in those with small AAAs (3.0 to 3.9 cm); the USPSTF noted, however, that, there are expert opinion-based recommendations in favor of periodic repeat ultrasonography for these patients.

Repeat abdominal ultrasound testing every 6 months has been recommended for men with abdominal aortic aneurysms greater than 4 cm in diameter, and every 2 years for men with smaller abdominal aortic aneurysms (Lederle, 2003).

Color flow duplex ultrasound scanning has been used as an surveillance modality for clinically significant endoleaks in patients who have undergone endovascular repair of AAAs.  Sun (2006) systematically reviewed the findings of diagnostic value of color duplex ultrasound (US) in the follow-up of endovascular repair of AAAs.  Studies comparing the diagnostic accuracy of color duplex US with that of computed tomographic (CT) angiography were included, and analysis was performed of the detection of endoleaks and measurement of aneurysm diameter.  A total of 21 studies (39 separate comparisons) met the criteria and were included for analysis.  Pooled estimates of sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV), and accuracy of color duplex US compared with CT angiography (with 95 % confidence interval [CI]) were 66 % (52 to 81 %), 93 % (89 to 97 %), 76 % (65 to 87 %), 90 % (86 to 95 %), and 91 % (86 to 97 %), respectively, for unenhanced color duplex US; and 81 % (52 to 100 %), 82 % (68 to 97 %), 58 % (26 to 90 %), 95 % (87 to 100 %), and 98 % (91 to 100%), respectively, for enhanced color duplex US.  The sensitivity in the detection of endoleak was significantly improved with contrast material-enhanced color duplex US compared with unenhanced color duplex US (p < 0.05); however, no significant difference was found regarding the specificity, PPV, NPV, and accuracy between unenhanced and enhanced color duplex US (p > 0.05).  Color duplex US was insensitive in measurement of aneurysm diameter compared with CT angiography in most situations.  The authors concluded that color duplex US is not as accurate as CT angiography and can not replace CT angiography in the follow-up of endovascular aortic repair of AAAs.  However, the use of contrast material-enhanced color duplex US resulted in improvement of diagnostic accuracy in the detection of endoleak and warrants further study.

Kim et al (2007) estimated the benefits, in terms of AAA-related and all-cause mortality, and cost-effectiveness of ultrasonography screening for AAA in a group that was invited to screening compared with a group that was not invited at a mean 7-year follow-up.  Population-based sample of 67,770 men aged 65 to 74 years were included in this analysis.  Patients with an AAA detected at screening had surveillance and were offered surgery after pre-defined criteria were met.  Mortality data were obtained after flagging on the national database.  Unit costs obtained from large samples were applied to individual event data for the cost analysis.  The hazard ratio was 0.53 (95 % CI: 0.42 to 0.68) for AAA-related mortality in the group invited for screening.  The rupture rate in men with normal results on initial ultrasonography has remained low: 0.54 rupture (CI: 0.25 to 1.02 ruptures) per 10,000 person-years.  In terms of all-cause mortality, the observed hazard ratio was 0.96 (CI: 0.93 to 1.00).  At the 7-year follow-up, cost-effectiveness was estimated at $19,500 (CI: $12,400 to $39,800) per life-year gained based on AAA-related mortality and $7,600 (CI: $3,300 to infinity) per life-year gained based on all-cause death.  Inclusion of deaths from aortic aneurysm at an unspecified site, which may include some thoracic aortic aneurysms, may have under-estimated the treatment effect.  The authors concluded that these findings from a large, pragmatic randomized trial showed that the early mortality benefit of screening ultrasonography for AAA is maintained in the longer term and that the cost-effectiveness of screening improves over time.

In a Cochrane review on screening for AAA, Cosford and Leng (2007) concluded that there is evidence of a significant reduction in mortality from AAA in men aged 65 to 79 years who undergo ultrasound screening.  However, there is insufficient evidence to demonstrate benefit in women.

Eckstein and colleagues (2009) stated that ultrasonography of the abdominal aorta is a safe and technically simple method of detecting AAAs.  These investigators performed a meta-analysis of population-based, randomized controlled trials (RCTs) of ultrasonographic screening for the detection of AAA.  A total of 4 RCTs showed that ultrasonographic screening was associated with a significant lowering of AAA-related mortality in men aged 65 to 80 after it had been performed for 3 to 5 years (risk reduction 44 %, odds ratio [OR] 0.56, 95 % CI: 0.44 to 0.72) and after it had been performed for 7 to 15 years (risk reduction 53 %, OR 0.47, 95 % CI: 0.25 to 0.90).  Screening of AAA was also associated with a significant lowering of the overall mortality after 7 to 15 years, but not in the first 5 years.  Ultrasonographic screening led to a significant increase in the number of elective AAA operations performed and to a 50 % reduction of the number of emergency operations for ruptured AAA.  The authors concluded that ultrasonographic screening for AAA is a technically simple diagnostic test that is associated with a major reduction of AAA-related mortality.  In view of the higher prevalence of AAA among the elderly, it is recommended that all men aged 65 or older and all men and women with a family history of AAA should be systematically screened.

Koelemay et al (2009) noted that the evidence-based guideline "Diagnosis and treatment of abdominal aortic aneurysm" is applicable to all patients with an atherosclerotic fusiform or ruptured AAA.  An AAA with a diameter less than 5.5 cm is treated conservatively and monitored by sonographic surveillance.  All patients are advised secondary prevention with anti-platelet therapy, statin therapy, treatment of hypertension and smoking cessation.  Depending on co-morbidity, the indication for an operation is an AAA diameter of 5.5 cm.  The anatomical characteristics of the AAA guides the choice for an open operation or endovascular aneurysm repair (EVAR).  In view of the lower peri-operative mortality, EVAR is the treatment of choice.  Due to the high prevalence of AAA in siblings of patients with an AAA, the screening of these family members should be considered.

Brown et al (2013) stated that small AAAs (3.0 cm to 5.4 cm in diameter) are monitored by US surveillance.  The intervals between surveillance scans should be chosen to detect an expanding aneurysm prior to rupture.  These researchers performed a meta-analysis to limit risk of aneurysm rupture or excessive growth by optimizing US surveillance intervals.  Individual patient data from studies of small AAA growth and rupture were assessed.  Studies were identified for inclusion through a systematic literature search through December 2010.  Study authors were contacted, which yielded 18 data sets providing repeated US measurements of AAA diameter over time in 15,471 patients.  Abdominal aortic aneurysms diameters were analyzed using a random-effects model that allowed for between-patient variability in size and growth rate.  Rupture rates were analyzed by proportional hazards regression using the modeled AAA diameter as a time-varying covariate.  Predictions of the risks of exceeding 5.5-cm diameter and of rupture within given time intervals were estimated and pooled across studies by random effects meta-analysis.  Abdominal aortic aneurysms growth and rupture rates varied considerably across studies.  For each 0.5-cm increase in AAA diameter, growth rates increased on average by 0.59 mm per year (95 % CI: 0.51 to 0.66) and rupture rates increased by a factor of 1.91 (95 % CI: 1.61 to 2.25). For example, to control the AAA growth risk in men of exceeding 5.5 cm to below 10 %, on average, a 7.4-year surveillance interval (95 % CI: 6.7 to 8.1) is sufficient for a 3.0-cm AAA, while an 8-month interval (95 % CI: 7 to 10) is necessary for a 5.0-cm AAA.  To control the risk of rupture in men to below 1 %, the corresponding estimated surveillance intervals are 8.5 years (95 % CI: 7.0 to 10.5) and 17 months (95 % CI: 14 to 22).  The authors concluded that in contrast to the commonly adopted surveillance intervals in current AAA screening programs, surveillance intervals of several years may be clinically acceptable for the majority of patients with small AAA.

Thompson et al (2013) noted that small AAAs (3.0 to 5.4 cm in diameter) are usually asymptomatic and managed by regular US surveillance until they grow to a diameter threshold (commonly 5.5 cm) at which surgical intervention is considered.  The choice of appropriate surveillance intervals is governed by the growth and rupture rates of small AAAs, as well as their relative cost-effectiveness.  These investigators provided the evidence base for small AAA surveillance strategies.  This was achieved by literature review, collation and analysis of individual patient data, a focus group and health economic modelling.  These researchers undertook systematic literature reviews of growth rates and rupture rates of small AAAs.  The databases MEDLINE, EMBASE on OvidSP, Cochrane Central Register of Controlled Trials 2009 Issue 4, ClinicalTrials.gov, and controlled-trials.com were searched from inception up until the end of 2009.  They also obtained individual data on 15,475 patients from 18 surveillance studies.  Systematic reviews of publications identified 15 studies providing small AAA growth rates, and 14 studies with small AAA rupture rates, up to December 2009 (later updated to September 2012).  The authors developed statistical methods to analyze individual surveillance data, including the effects of patient characteristics, to inform the choice of surveillance intervals and provide inputs for health economic modelling.  They updated an existing health economic model of AAA screening to address the cost-effectiveness of different surveillance intervals.  In the literature reviews, the mean growth rate was 2.3 mm/year and the reported rupture rates varied between 0 and 1.6 ruptures per 100 person-years.  Growth rates increased markedly with aneurysm diameter, but insufficient detail was available to guide surveillance intervals.  Based on individual surveillance data, for each 0.5-cm increase in AAA diameter, growth rates increased by about 0.5 mm/year and rupture rates doubled.  To control the risk of exceeding 5.5 cm to below 10 % in men, on average a 7-year surveillance interval is sufficient for a 3.0-cm aneurysm, whereas an 8-month interval is necessary for a 5.0-cm aneurysm.  To control the risk of rupture to below 1 %, the corresponding estimated surveillance intervals are 9 years and 17 months.  Average growth rates were higher in smokers (by 0.35 mm/year) and lower in patients with diabetes (by 0.51 mm/year).  Rupture rates were almost 4-fold higher in women than men, doubled in current smokers and increased with higher blood pressure.  Increasing the surveillance interval from 1 to 2 years for the smallest aneurysms (3.0 to 4.4 cm) decreased costs and led to a positive net benefit.  For the larger aneurysms (4.5 to 5.4 cm), increasing surveillance intervals from 3 to 6 months led to equivalent cost-effectiveness.  The authors concluded that surveillance intervals of several years are clinically acceptable for men with AAAs in the range 3.0 to 4.0 cm.  Intervals of around 1 year are suitable for 4.0 to 4.9-cm AAAs, whereas intervals of 6 months would be acceptable for 5.0 to 5.4-cm AAAs.  These intervals are longer than those currently employed in the UK AAA screening programs.  Lengthening surveillance intervals for the smallest aneurysms was also shown to be cost-effective.  Future work should focus on optimizing surveillance intervals for women, studying whether or not the threshold for surgery should depend on patient characteristics, evaluating the usefulness of surveillance for those with aortic diameters of 2.5 to 2.9 cm, and developing interventions that may reduce the growth or rupture rates of small AAAs.

On behalf of the USPSTF, Guirguis-Blake et al (2014) systematically reviewed evidence about the benefits and harms of ultrasonography screening for AAAs in asymptomatic primary care patients.  Data sources included MEDLINE, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials (January 2004 through January 2013), clinical trial registries, reference lists, experts, and a targeted bridge search for population-based screening RCTs through September 2013.  English-language, population-based, fair- to good-quality RCTs and large cohort studies for AAA screening benefits as well as RCTs and cohort and registry studies for harms in adults with AAA were selected for analysis.  Reviews of 4 RCTs involving 137,214 participants demonstrated that 1-time invitation for AAA screening in men aged 65 years or older reduced AAA rupture and AAA-related mortality rates for up to 10 and 15 years, respectively, but had no statistically significant effect on all-cause mortality rates up to 15 years.  Screening was associated with more overall and elective surgeries but fewer emergency operations and lower 30-day operative mortality rates at up to 10- to 15-year follow-up.  One RCT involving 9,342 women showed that screening had no benefit on AAA-related or all-cause mortality rates.  The authors concluded that one-time invitation for AAA screening in men aged 65 years or older was associated with decreased AAA rupture and AAA-related mortality rates; but had little or no effect on all-cause mortality rates.

LeFevre (2014) reported the update of the 2005 UUSPSTF recommendation on screening for AAA.  The USPSTF commissioned a systematic review that assessed the evidence on the benefits and harms of screening for AAA and strategies for managing small (3.0 to 5.4 cm) screen-detected AAAs.  These recommendations apply to asymptomatic adults aged 50 years or older.

• The USPSTF recommends 1-time screening for AAA with ultrasonography in men aged 65 to 75 years who have ever smoked. (B recommendation).
• The USPSTF recommends that clinicians selectively offer screening for AAA in men aged 65 to 75 years who have never smoked. (C recommendation).
• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AAA in women aged 65 to 75 years who have ever smoked. (I statement).
• The USPSTF recommends against routine screening for AAA in women who have never smoked. (D recommendation).

Abdominal Aortic Aneurysm Screening in Women

Ulug and colleagues (2016) stated that although women represent an increasing proportion of those presenting with abdominal aortic aneurysm (AAA) rupture, the current prevalence of AAA in women is unknown.  The contemporary population prevalence of screen-detected AAA in women was investigated by both age and smoking status.  These researchers performed a systematic review of studies screening for AAA, including over 1,000 women, aged at least 60 years, done since the year 2000.  Studies were identified by searching Medline, Embase and CENTRAL databases until January 13, 2016.  Study quality was assessed using the Newcastle-Ottawa scoring system.  A total of 8 studies were identified, including only 3 based on population registers.  The largest studies were based on self-purchase of screening.  Altogether 1,537,633 women were screened.  Overall AAA prevalence rates were very heterogeneous, ranging from 0.37 to 1.53 %: pooled prevalence 0.74 (95 % confidence interval [CI]: 0.53 to 1.03) %.  The pooled prevalence increased with both age (more than 1 % for women aged over 70 years) and smoking (more than 1 % for ever smokers and over 2 % in current smokers).  The authors concluded that the current population prevalence of screen-detected AAA in older women is subject to wide demographic variation.  However, in ever smokers and those over 70 years of age, the prevalence is over 1 %.

Chabok and associates (2016) noted that 4 randomized trials of men aged 65 to 80 years showed that aneurysm-related mortality was reduced by 40 % by ultrasound screening.  Screening is considered economically viable when the prevalence of abdominal aortic aneurysm (AAA) is 1.0 % or higher.  This is not the case for women, in whom the prevalence of AAA is less than 1 %.  These investigators determined the prevalence of AAA 3.0 cm or larger in women screened with ultrasound imaging, the risk factors associated with AAA in this population, and whether high-risk groups can be identified with an AAA prevalence of 1 % or greater.  Demographic data and risk factors were collected from the first 50,000 women who attended for private cardiovascular screening in the UK.  Tests included ultrasound screening for AAA, ankle brachial pressure index (ABPI), carotid duplex imaging for carotid atherosclerosis, and electrocardiography for atrial fibrillation.  AAA was detected in 82 of 50,000 women screened; these aneurysms were rare below the age of 66 years (7 of 24,499).  In the 66 to 85 years age group there were 72 AAAs in 25,170 women (0.29 %).  Univariable analysis demonstrated that a history of stroke/transient ischemic attack (TIA), hypertension, smoking, atrial fibrillation, ABPI of less than 0.9 and internal carotid artery stenosis of at least 50 % were associated with an increased prevalence of AAA (p < 0·001).  In multivariable linear logistic regression of risk factors, age 76 years or more, history of stroke/TIA, hypertension and smoking were independent predictors of AAA.  This model had an area under the receiver operating characteristic (ROC) curve (AUC) of 0.711 (95 % CI: 0.649 to 0.772) and could identify 2,235 women who had 22 AAAs (prevalence 0.98 %).  By adding ABPI, atrial fibrillation and carotid stenosis, the prediction improved to an AUC of 0.775 (0.724 to 0.826).  This model could identify 3,701 women who had 58 AAAs (prevalence 1.57 %).  The authors concluded that this report should stimulate consideration of a targeted AAA screening program for women aged over 65 years.

Soderberg and colleagues (2017) reported on the natural history of a population-based cohort of 70-year old women with screening detected dilated aortas, and systematically reviewed publications reporting the rate of intact infra-renal aneurysm repair in women.  In a previous study, 5,140 (74 %) of 6,925 invited women attended an US examination of the abdominal aorta at age 70 years.  All 52 women with screening detected sub-aneurysms (SA, diameter of 25 to 29 mm) and AAA (diameter of greater than or equal to 30 mm), were followed for 5 years with US.  Infra-renal aortic diameters, AAA repair, all-cause and AAA specific mortality, and risk factors were recorded.  In addition, a systematic review was conducted of the rate of intact infra-renal aneurysm repair in women.  A total of 33 (0.6 %) women had a SA at the age of 70; 2 (6 %) declined follow-up, 5 (15 %) had died, and 26 were re-examined after 5 years follow-up at age 75; 12 of 26 (46 %) had progressed to AAAs, where 1 was directly qualified for surgery.  Smoking (p = 0.010) and aortic diameter (p = 0.040) were associated with progression to AAA.  A total of 19 (0.4 %) women had an AAA at age 70; 2 (11 %) had died, 6 (32 %) had been electively repaired with no 30-day mortality, and 11 (58 %) had an AAA still under surveillance after 5 years follow-up at age 75 years.  In the systematic search, 4 studies with heterogeneous cohorts were identified and data on natural history were extracted and reviewed.  The authors concluded that screening detected AAAs and sub-aneurysms are clinically relevant in women.  Within 5 years of detection a high proportion of AAAs required elective surgery, and a high proportion of sub-aneurysms progress to AAAs.  Consequently, surveillance of sub-aneurysms in women with reasonable life expectancy can be considered.  Publications on repair rate in women with intact AAAs were scarce and heterogeneous.

Furthermore, an UpToDate review on “Screening for abdominal aortic aneurysm” (Mohler, 2017) states that “The prevalence of AAAs is negligible in individuals under the age of 60, particularly women, but then increases dramatically with age.  Screening studies show that AAA occurs in 4 to 9 % of individuals over the age of 60.  However, most (57 to 88 %) of these aneurysms are ≤ 3.5 cm in diameter.  Clinically important aneurysms over 4.0 cm in diameter are present in about 1 % of men between the ages of 55 and 64; the prevalence increases by 2 to 4 % per decade thereafter … AAAs are 4 to 6 times more common in men than in women.  In addition, AAAs develop in women about 10 years later than in men.  A model to identify women with multiple cardiovascular risk factors who are at particularly high risk for AAA and may benefit from screening has been developed combining 2 United States data sets, but remains to be validated in other populations … Only one study examined population-based screening in women, a population in whom the prevalence of AAA is significantly lower than in men (1.3 versus 7.6 %).  Screening had no effect on AAA-related mortality (OR 1.0, 95 % CI 0.14-7.07) or all-cause mortality (OR 1.05, 0.92-1.19) at 5-year and 10-year follow-up … The USPSTF advises against screening women who have never smoked, but conclude that evidence is insufficient to assess the benefits and harms of screening women aged 65 to 75 who have ever smoked … The Society for Vascular Surgery issued updated guidelines in 2009 recommending one-time screening for all men older than 65 (and at 55 if family history is positive) and screening for women older than 65 who have smoked or have a family history.  The guidelines cite that, although the prevalence of AAA is lower in women than men, rupture rates are higher in women and life expectancy is longer … The Canadian Society for Vascular Surgery recommends screening for men between age 65 and 75 who are candidates for surgery.  Recommendations are not to screen women > 65 years on a population basis, but to individualize screening for women with multiple risks (smoking, cerebrovascular disease, and family history)”.

The Canadian Task Force on Preventive Health Care’s “Recommendations on screening for abdominal aortic aneurysm in primary care” (2017) stated that “Women have much lower rates of AAA than men, and there is no direct evidence that screening women has a positive impact on their health”.  The Canadian Task Force on Preventive Health Care recommended not screening women for AAA (strong recommendation; very low quality of evidence).

The above policy is based on the following references: