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Pharmacy Clinical Policy Bulletins
Aetna Non-Medicare Prescription Drug Plan
Subject: Angiotensin-Converting Enzyme Inhibitors/Combinations

Status Drug PR PR-QL PR-AL ST M EX‡
P benazepril   X      
P captopril   X      
P enalapril   X      
P fosinopril   X      
P lisinopril   X      
P moexipril   X      
P quinapril   X      
P trandolapril   X      
P benazepril/HCTZ [HCTZ = hydrochlorothiazide]          
P captopril/HCTZ          
P enalapril/HCTZ          
P fosinopril/HCTZ          
P lisinopril/HCTZ          
P moexipril/HCTZ          
P quinapril/HCTZ          
P Altace®  (ramipril)   X      
FE Accupril®  (quinapril)   X   X X
FE Accuretic®  (quinapril/HCTZ)       X X
FE Aceon®  (perindopril)   X     X
FE Capoten®  (captopril)   X     X
FE Capozide®  (captopril/HCTZ)         X
FE Lotensin®  (benazepril)   X     X
FE Lotensin HCT®  (benazepril/HCTZ)         X
FE Mavik®  (trandolapril)   X     X
FE Monopril®  (fosinopril)   X     X
FE Monopril HCT®  (fosinopril/HCTZ)         X
FE Prinivil®  (lisinopril)   X     X
FE Prinzide®  (lisinopril/HCTZ)         X
FE Uniretic®  (moexipril/HCTZ)         X
FE Univasc®  (moexipril)   X     X
FE Vaseretic®  (enalapril/HCTZ)         X
FE Vasotec®  (enalapril)   X     X
FE Zestoretic®  (lisinopril/HCTZ)         X
FE Zestril®  (lisinopril)   X     X
FE Lytensopril Pak®  (lisinopril/nutritional supplement cap pak)         X


Policy:

  1. Precertification Criteria

    2. Under some plans, including plans that use an open or closed formulary, angiotensin-converting enzyme inhibitors Accupril, Aceon, Altace, benazepril, Capoten, captopril, enalapril, fosinopril, lisinopril,  Lotensin,  Mavik, moexipril, Monopril, Prinivil, quinapril, trandolapril, Univasc, Vasotec, and Zestril are subject to precertification.  If precertification requirements apply, Aetna considers these to be medically necessary for those members who meet the following precertification criteria:

     

    According to the manufacturer, the angiotensin converting enzyme inhibitors Accupril, Aceon, Altace, benazepril, Capoten, captopril, enalapril, fosinopril, lisinopril, Lotensin, Mavik, moexipril, Monopril, Prinivil, quinapril, trandolapril, Univasc, Vasotec and Zestril can be dosed up to a maximum daily dose at the interval(s) as indicated in the table below. A quantity of each drug will be considered medically necessary as indicated in the table below:

    Drug Maximum Daily Dose/ Dosing Interval Dosage Strength Quantity Limits
    quinapril, Accupril 80 mg/ once or twice daily 5 mg, 10 mg, 20 mg Up to 60 tablets in 30 days
    quinapril, Accupril 80 mg/ once or twice daily 40 mg None
    Aceon 16 mg/ Once or twice daily 2 mg, 4 mg Up to 60 tablets in 30 days
    Aceon 16 mg/ Once or twice daily 8 mg None
    Altace 20 mg/ Once or twice daily 1.25 mg, 2.5 mg, 5 mg Up to 60 capsules in 30 days
    Altace 20 mg/ Once or twice daily 10 mg None
    captopril, Capoten 450 mg/ twice or three times daily 12.5 mg, 25 mg, 50 mg Up to 90 tablets in 30 days
    captopril, Capoten 450 mg/ twice or three times daily 100 mg None
    benazepril, Lotensin 80 mg/ Once or twice daily 5 mg, 10 mg, 20 mg Up to 60 tablets in 30 days
    benazepril, Lotensin 80 mg/ Once or twice daily 40 mg None
    trandolapril, Mavik 8 mg/ Once or twice daily 1 mg, 2 mg Up to 60 tablets in 30 days
    trandolapril, Mavik 8 mg/ Once or twice daily 4 mg None
    fosinopril, Monopril 80 mg/ Once or twice daily 10 mg, 20 mg Up to 60 tablets in 30 days
    fosinopril, Monopril 80 mg/ Once or twice daily 40 mg None
    lisinopril, Prinivil, Zestril 80 mg/ Once daily 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg Up to 60 tablets in 30 days
    lisinopril, Prinivil, Zestril 80 mg/ Once daily 40 mg None
    moexipril, Univasc 30 mg/ Once or twice daily 7.5 mg Up to 60 tablets in 30 days
    Univasc 30 mg/ Once or twice daily 15 mg None
    enalapril, Vasotec 40 mg/ Once or twice daily 2.5 mg, 5 mg, 10 mg Up to 60 tablets in 30 days
    enalapril, Vasotec 20 mg/ Once or twice daily 20 mg None


    For coverage of additional quantities, a member's treating physician must request prior authorization through the Pharmacy Management Precertification Unit. Additional quantities of these angiotensin-converting enzyme inhibitors will be considered medically necessary for those members who meet ANY of the following criteria:

    • Member requires a dose including half tablets OR
    • Member's dose is being titrated by physician (3 month limit) OR
    • Member has had intolerance to drug administered as a single daily dose OR
    • Member has failed the maximum labeled dose AND has a therapeutic response to a higher dose OR
    • Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose.


  2. Step Therapy Criteria

    3. Under some plans, including plans that use an open or closed formulary, Accupril and Accuretic are subject to step-therapy.  Aetna considers Accupril and Accuretic to be medically necessary for those members who meet the following step-therapy criterion:

    A documented trial of one month of the drug's generic equivalent.

    If it is medically necessary for a member to be treated initially with a medication subject to step-therapy, the member's treating physician may contact the Aetna Pharmacy Management Precertification Unit to request coverage as a medical exception at 1-800-414-2386. (See criteria under section II below)

  3. Medical Exception Criteria

    4. Aceon, Accupril, Accuretic, Capoten, Capozide, Lytensopril Pak Lotensin, Lotensin HCT, Mavik, Monopril, Monopril HCT, Prinivil, Prinzide, Uniretic, Univasc, Vasotec, Vaseretic, Zestoretic and Zestril are currently listed on the Aetna Formulary Exclusions List.* Therefore, these are excluded from coverage for members enrolled in prescription drug benefit plans that use a closed formulary, unless a medical exception is granted. Aetna considers Aceon, Accupril, Accuretic, Capoten, Capozide, Lytensopril Pak Lotensin, Lotensin HCT, Mavik, Monopril, Monopril HCT, Prinivil, Prinzide, Uniretic, Univasc, Vasotec, Vaseretic, Zestril, or Zestoretic to be medically necessary for those members who meet the criteria as specified below:

    For Accupril, Accuretic, Capoten, Capozide, Lotensin, Lotensin HCT, Mavik, Monopril, Monopril HCT, Prinivil, Prinzide, Univasc, Vasotec, Vaseretic, Zestril, and Zestoretic:

    A documented:

    • Contraindication to the drug's generic equivalent OR
    • Intolerance to the drug's generic equivalent OR
    • Allergy to the drug's generic equivalent OR
    • Failure of an adequate trial of one month of the drug's generic equivalent.

    For Aceon

    A documented:

    • Intolerance to two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives OR
    • Contraindication to two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives OR
    • Allergy to two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives OR
    • Failure of an adequate trial of one month each of two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives.

    For Uniretic: 

    A documented:

    • Intolerance to two preferred angiotensin-converting enzyme inhibitor (ACEI)/ hydrochlorothiazide combination alternatives OR,
    • Contraindication to two preferred angiotensin-converting enzyme inhibitor (ACEI)/ hydrochlorothiazide combination alternatives OR,
    • Allergy to two preferred angiotensin-converting enzyme inhibitor (ACEI)/ hydrochlorothiazide combination alternatives OR,
    • Failure of an adequate trial of one month each of two preferred angiotensin-converting enzyme inhibitor (ACEI)/hydrochlorothiazide combination alternatives.

    For Lytensopril Pak;

    A documented:

    • Intolerance to two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives (one of which should be lisinopril ) OR
    • Contraindication to two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives (one of which should be lisinopril ) OR
    • Allergy to two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives (one of which should be lisinopril )  OR
    • Failure of an adequate trial of one month each of two preferred angiotensin-converting enzyme inhibitor (ACEI) alternatives (one of which should be lisinopril )

Place of Service:

Outpatient

The above policy is based on the following references:
  1. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. 2006.
  2. USP DI® Drug Information For The Health Care Professional - 26th Ed. (online from www.statref.com) Thomson Micromedex, Greenwood Village, CO. 2006 .
  3. AHFS Drug Information® with AHFSfirstReleases®. (online from www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. 2006.
  4. DRUGDEX® System: Klasco RK (Ed):DRUGDEX® System. Online edition. Thomson Micromedex, Greenwood Village, CO.
  5. PDR® Electronic Library, Thomson Micromedex, Greenwood Village, Colorado (Edition expires 2006).
  6. Tu K et al.  The Striking Effect of the Heart Outcomes Prevention evaluation (HOPE) on Ramipiril Prescribing in Ontario.  CMAJ 2003; 168:  553-7.
  7. Maia LN et al.  Prospective Evaluation Comparing the Effects of Enalapril and Losartan in Left ventricular Remodeling After acute Myocardial Infarction.  Am Heart J. 2003; 145:  E21.
  8. PROGRESS Collaborative Group.  Effects of a Perindopril-Based Blood Pressure Lowering Regimen on Cardiac Outcomes among Patients with Cerebrovascular Disease.  Eur Heart J. 2003;24:475-84.
  9. Wing LM et al.  A Comparison of Outcomes with Angiotensin-Converting-Enzyme Inhibitors and Diuretics for Hypertension in the Elderly.  N Engl J Med. 2003; 348:  583-92.
  10. Dickstein K et al.  Effects of Losartan and Captopril on Mortality and Morbidity in High-Risk Patients After Acute Myocardial Infarction:  The OPTIMAAL Randomized Trial.  Lancet. 2002; 360:  752-60.
  11. White WB, MD et al.  Preventing Increases in Early-Morning Blood Pressure, Heart Rate, and the Rate-Pressure Product with Controlled Onset Extended Release Verapamil at Bedtime Versus Enalapril, Losartan, and Placebo on Arising.  Am Heart J.  2002; 144:  657-65.
  12. Wright JT, MD, PhD et al.  Effect of Blood Pressure Lowering and Antihypertensive Drug Class on Progression of Hypertensive Kidney Disease (Results From the AASK Trial).  JAMA.  2002; 288:  2421-31.
  13. Cordonnier, et al.  Role of ACE Inhibitors in Patients with Diabetes Mellitus. Drugs 2001:61 (13):1883-1892.
  14. Mann, JFE, et al.  Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril:  The HOPE Randomized Trial. Ann Intern Med.  April 17, 2001;134(8):629-636.
  15. Chalmers, J, et al.  PROGRESS Management Committee, PROGRESS (Perindopril Protection Against Recurrent Stroke Study): regional characteristics of the study population at baseline. J of Hypertension. 2000,1(suppl 1):S13-S19.
  16. Hurst, M, Jarvis, Blair.  Perindopril, An Updated Review of its Use in Hypertension. AIDS Drugs 2001;61(6):867-96.
  17. Pfeffer MA, et al. The continuation of the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) Trial. Am Heart J. September 2001;142(3).     
  18. Devereux, RB, et al.  Effects of Once-Daily Angiotensin-Converting Enzyme Inhibition and Calcium Channel Blockade-Based Antihypertensive Treatment Regimens on Left Ventricular Hypertrophy and Diastolic Filling in Hypertension, The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement  (PRESERVE) Trial.  Circulation.  September 11, 2001;1041248-1254.
  19. Cutler J.  Which drug for treatment of hypertension? Lancet 1999;353:604-05.
  20. Parmley WW.  Evolution of angiotensin-converting enzyme inhibition in hypertension, heart failure, and vascular protection.  Am J Med. 1998; 105(1A): 27S-31S.
  21. Davies MK, Gibbs GR, Lip GYH.  ABC of heart failure: Management: diuretics, ACE inhibitors, and nitrates.  BMJ. 2000;320:428-31.
  22. Flather MD, Yusuf S, Kaber L, et al.  Long-term ACE-inhibitor therapy inpatients with heart failure or left-ventricular dysfunction; a systematic overview of data from individual patients.  Lancet. 2000;355:1575-81.
  23. The Heart Outcomes Prevention Evaluation Study Investigators.  Effect of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.  N Engl J Med. 2000;342:145-53.Chaturvedi N.  HOPE and extension of the indications for ACE inhibitors?  Lancet. 2000;355:246-7.
  24. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy.  Lancet. 2000;355:253-59.
  25. Francis GS.  ACE inhibition in cardiovascular disease.  N Engl J Med. 2000;342:201-2.
  26. Exner DV, et al.  Lesser Response to Angiotensin-Converting-Enzyme Inhibitor Therapy in Black as Compared with White Patients with Left Ventricular Dysfunction. N Engl J Med. May 3, 2001;344(18): 1351-7.
  27. Agondoa LY, et al.  Effect of Ramipril vs. Amlodipine on Renal Outcomes in Hypertensive Nephrosclerosis, A Randomized Controlled Trial.  JAMA. June 6, 2001;285(21):2719-2728.
  28. Swislocki AL et al. Renal Effects of Angiotensin-Converting-Enzymes Inhibitors that Result in Cost Savings and Improved Patient Outcomes. Am J Managed Care.  March 2001;7(3):283-295.
  29. The ACE Inhibitors in Diabetic Nephropathy Trialist Group, Should All Patients with Type 1 Diabetes Mellitus and Microalbuminuria Receive Angiotensin-Converting Enzyme Inhibitors? Ann Inter Med. March 6, 2001;134(5):370-79.
  30. Krumhotz HM, et al. Aspirin and Angiotensin-Converting Enzyme Inhibitors Among Elderly Survivors of Hospitalization for an Acute Myocardial Infarction. Arch Intern Med. February 26, 2001;161:538-544.
  31. Massie BM, et al. Toleration of High Doses of Angiotensin-Converting Enzyme Inhibitors in Patients with Chronic Heart Failure, Results from the ATLAS Trial. Arch Intern Med. January 22, 2001;161:165-171.
  32. Lonn, EM, et al. Effects of Ramipril and Vitamin E on Atherosclerosis, The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE). Circulation. February 20, 2001;103:919-25.
  33. Mason, JM, et al.  Safety and costs of initiating angiotensin converting enzyme inhibitors for heart failure in primary care: analysis of individual patient data from studies of left ventricular dysfunction. BMJ. November 4, 2000;321:1113-1116.
  34. Echemann, M et al.  Determinants of angiotensin-converting enzyme inhibitor prescription in severe heart failure with left ventricular systolic dysfunction: The EPICAL study. Am Heart J. April, 2000;139(4).
  35. Simpson E, Jarvis B. Lisinopril, A review of its Use in Congestive Heart Failure. ADIS Drug. May 2000;59(5):1149-1167.
  36. Flavel C,  Stevenson LW. Taking Heart with Heart Failure, Circulation. October 30, 2001;104;e89-e91.
  37. Vasan, RS, et al. Impact of High Normal Blood Pressure on the Risk of Cardiovascular Disease. N Engl J Med. November 1, 2001;345(18):1291-7.
  38. Yusuf S., et al. Ramipril and the Development of Diabetes. JAMA. October 17, 2001;286(15): 1882-1885.
  39. Jafar TH, et al. Angiotensin-Converting Enzyme Inhibitors and Progression of Nondiabetic Renal Disease, A meta-analysis of patient-level data. Ann Intern Med. July 17, 2001;135(2):73-87.
  40. The Seventh Report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure.  JAMA. 2003;289:2560-71.
  41. ALLHAT Officers and Coordinators.  Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).  JAMA 2002; 288: 2981-97. USP DI® Drug Information For The Health Care Professional - 26th Ed. (online from www.statref.com) Thomson Micromedex, Greenwood Village, CO. 2006
  42. Hunt SA. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure) J Am Coll Cardiol 2005: 46;1-82. Online at: http://content.onlinejacc.org/cgi/reprint/46/6/e1.
  43. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA Guidelines for the Management of Patients With (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): A Collaborative Report From the AAVS/SVS, SCAI, SIR, SVMB, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Artierial Disease). American College of Cardiology Web Site. Available at: http://www.acc.org/clinical/guidelines/pad/index/pdf.
  44. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction-executive summary: a report of the ACC/AHA Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines on the Management of Patients With Acute Myocardial Infarction. J Am Coll Cardiol 2004;44:671-719.

 

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

January 01, 2007
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