Close Window
Aetna Medicare
Aetna Aetna
Pharmacy Clinical Policy Bulletins
Aetna Medicare Prescription Drug Plan
Subject: Angiotensin II Receptor Antagonists (AIIRAs, ARBs)/Combinations

Status Drug PR-B/D PR PR-QL PR-AL ST M EX‡ TOC§
C Cozaar®  (losartan)     X        
C Diovan HCT®  (valsartan/hydrochlorothiazide)     X        
C Diovan®  (valsartan)     X        
C Hyzaar®  (losartan/hydrochlorothiazide)     X        
NC Atacand HCT®  (candesartan/hydrochlorothiazide)     X   X X X
NC Atacand®  (candesartan)     X   X X X
NC Avalide®  (irbesartan/hydrochlorothiazide)     X   X X X
NC Avapro®  (irbesartan)     X   X X X
NC Benicar HCT®  (olmesartan/hydrochlorothiazide)     X   X X X
NC Benicar®  (olmesartan)     X   X X X
NC Micardis HCT®  (telmisartan/hydrochlorothiazide)     X   X X X
NC Micardis®  (telmisartan)     X   X X X
NC Teveten HCT®  (eprosartan/hydrochlorothiazide)         X X X
NC Teveten®  (eprosartan)     X   X X X


Policy:

  1. Precertification Criteria

    2. Under some plans, including plans that use an open or closed formulary, Atacand, Atacand HCT Avalide, Avapro, Benicar, Benicar HCT, Cozaar, Diovan, Diovan HCT, Hyzaar, Micardis, Micardis HCT, and Teveten are subject to precertification.  If precertification requirements apply Aetna considers Atacand, Atacand HCT Avalide, Avapro, Benicar, Benicar HCT, Cozaar, Diovan, Diovan HCT, Hyzaar, Micardis, Micardis HCT, and Teveten to be medically necessary for those members who meet the following precertification criteria:

    Quantity limits:  

    According to the manufacturer, the angiotensin II receptor antagonists and angiotensin II receptor antagonist combinations 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
    Atacand 32 mg/ Once daily 4, 8, 16 mg Up to 60 tablets in 30 days
    Atacand 32 mg/ Once daily 32 mg None
    Atacand HCT 32 mg/ Once daily 16/12.5 mg Up to 60 tablets in 30 days
    Atacand HCT 32 mg/ Once daily 32/12.5 mg None
    Avalide 300 mg/ Once daily 150/12.5 mg Up to 30 tablets in 30 days
    Avalide 300 mg/ Once daily 300/12.5 mg None
    Avapro 300 mg/ Once daily 75 mg, 150 mg Up to 30 tablets in 30 days
    Avapro 300 mg/ Once daily 300 mg None
    Benicar 40 mg/ Once daily 5 mg, 20 mg Up to 30 tablets in 30 days
    Benicar 40 mg/ Once daily 40 mg None
    Benicar HCT 40 mg/ Once daily 20/12.5 mg Up to 30 tablets in 30 days
    Benicar HCT 40 mg/ Once daily 40/12.5 mg, 40/25 mg None
    Cozaar 100 mg/ Once daily 25 mg, 50 mg Up to 60 tablets in 30 days
    Cozaar 100 mg/ Once daily 100 mg None
    Diovan 320 mg/ Once daily 40, 80, 160 mg Up to 60 tablets in 30 days
    Diovan 320 mg/ Once daily 320 mg None
    Diovan HCT 320 mg/ Once daily 80/12.5 mg Up to 30 tablets in 30 days
    Diovan HCT 320 mg/ Once daily 160/12.5mg, 160/25 mg None
    Hyzaar 100 mg/ Once daily 50/12.5 mg Up to 30 tablets in 30 days
    Hyzaar 100 mg/ Once daily 100/25 mg, 100/12.5 mg None
    Micardis 80 mg/ Once daily 20 mg, 40 mg Up to 30 tablets in 30 days
    Micardis 80 mg/ Once daily 80 mg None
    Micardis HCT 80 mg/ Once daily 40/12.5 mg Up to 30 tablets in 30 days
    Micardis HCT 80 mg/ Once daily 80/12.5 mg None
    Teveten 800 mg/ Once daily 400 mg Up to 60 tablets in 30 days
    Teveten 800 mg/ Once daily 600 mg None


    For coverage of additional quantities, a member's treating physician must request prior authorization through the Aetna Pharmacy Management Precertification Unit.  Additional quantities of these angiotensin II receptor antagonists 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 has a diagnosis of heart failure, NYHA class II-IV or left ventricular dysfunction, post-myocardial infarction (Diovan only) 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, Atacand, Atacand HCT, Avalide, Avapro, Benicar, Benicar HCT, Micardis, Micardis HCT, Teveten and Teveten HCT are subject to step-therapy.  Aetna considers Atacand, Atacand HCT, Avalide, Avapro, Benicar, Benicar HCT, Micardis, Micardis HCT, Teveten and Teveten HCT to be medically necessary for those members who meet the following step-therapy criterion:

    A documented trial of one month each of BOTH losartan (Cozaar/Hyzaar) AND valsartan (Diovan/ Diovan-HCT) - alternatives on the Aetna Medicare Preferred Drug List.

    If it is medically necessary for a member to be treated initially with a medication subject to step-therapy, or if the member meets transition of coverage (TOC) criteria for a medication subject to TOC,  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 III below.)


  3. Medical Exception Criteria

    4. Atacand, Atacand HCT, Avalide, Avapro, Benicar, Benicar HCT, Micardis, Micardis HCT, Teveten and Teveten HCT are currently Not Covered Part D drugs under the Aetna Medicare Prescription Drug Plan.*  Therefore, they 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 Atacand, Atacand HCT, Avalide, Avapro, Benicar, Benicar HCT, Micardis, Micardis HCT, Teveten and Teveten HCT to be medically necessary for those members who meet ANY of the following criteria:

    A.  A documented:

    • Contraindication to both covered angiotensin II antagonists, losartan (Cozaar/Hyzaar) AND valsartan (Diovan/ Diovan-HCT) OR
    • Intolerance to both covered angiotensin II antagonists, losartan (Cozaar/Hyzaar) AND valsartan (Diovan/ Diovan-HCT) OR
    • Allergy to both covered angiotensin II antagonists, losartan (Cozaar/Hyzaar) AND valsartan (Diovan/ Diovan-HCT) OR
    • Failure of an adequate trial of one month each of both covered angiotensin II antagonists, losartan (Cozaar/Hyzaar) AND valsartan (Diovan/ Diovan-HCT)

    OR

    B.  Transition of Coverage:

    • Member is within 90 days of his or her effective date of enrollment
    • Member is stable on Atacand, Atacand HCT, Avalide, Avapro, Benicar, Benicar HCT, Micardis, Micardis HCT, Teveten or Teveten HCT for 30 days or longer

    If applicable, quantity limits, age or gender edits will apply.  Transition of Coverage approval is valid one year from the date of request.

    If the member has been a Medicare member for 91 days or longer and is not residing in a LTC facility then standard precertification, step-therapy, or medical exception criteria will apply.


* Coverage is provided through a Medicare Prescription Drug Plan Sponsor with a Medicare contract and benefits, limitations, service areas and premiums are subject to change on January 1 of each year.

Place of Service:

Outpatient

The above policy is based on the following references:
  1. Cohn JN, et al. A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure. New Eng J Med. Dec 6, 2001; 345(23(:1667-75.
  2. Lewis ED, et al.  Renoprotective effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes.  New Eng J Med. Sept. 20, 2001; 345(12):851-60.
  3. Viberti G, Wheeldon, NM for the MARVAL Investigators.  Microalbuminuria with valsartan in patients with type 2 diabetes mellitus.  A blood pressure independent effect.  Circulation. 2002;106:672-678.
  4. Kjeldsen SE, et al. for the LIFE Study Group.  Effects of Losartan on Cardiovascular Morbidity and Mortality in Patients with Isolated Systolic Hypertension and Left Ventricular Hypertrophy, A Losarten Intervention for Endpoint Reduction (LIFE) Substudy. JAMA. 2002;288:1491-1498.
  5. Dickstein K, Kjekshus J, and the OPTIMAAL Steering Committee, for the OPTIMAAL Study Group, Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Lancet. 2002;360:752-60.
  6. Wong M, et al, for the Val-HeFT Heart Failure Trial Investigators. Valsartan Benefits Left Ventricular Structure and Function in Heart Failure: Val-HeFT Echocaardiographic Study.  J Amer Coll Cardiology. September 2002; 40(5):970-5.
  7. Goa KL & Wagstaff AJ.  Losartan potassium: A review of its pharmacology, clinical efficacy and tolerability in the management of hypertension.  Drugs. 1996; 51(5): 820-845.
  8. Black HR et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: Efficacy, tolerability and safety compared to an angiotensin converting enzyme inhibitor lisinopril. J. of Human Hypertension. 1997; 11:483-489. 
  9. Grun A et al.  A comparison of the efficacy and tolerability of a new angiotensin II antagonist, valsartan, with enalapril in patients with mild-to-moderate essential hypertension [abstract]. Eur Heart J. 1995 Aug: 16 Suppl: 61.
  10. Gradman AH et al.  A randomized, placebo-controlled, double-blind parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension.  Hypertension. 1995; 25: 1345-1350.
  11. Himmelmann A et al.  Long-term effects of losartan on blood pressure and left ventricular structure in essential hypertension.  J Hum Hypertens. 1996; 10(11): 729-734.
  12. Graham MR, Allcock NM.  Irbesartan Substitution for Valsartan or Losartan in Treating Hypertension.  Ann Pharmacother. 2002 December; 36:1840-4.
  13. Basile J.  Analysis of Recent Papers in Hypertension. J Clin Hypertens. 2002; 4(4):295-300.
  14. Sicea DA, Weber M. The Losartan Intervention for Endpoint Reduction (LIFE) Trial – Have Angiotensin-Receptor Blockers Come of Age? J Clin Hypertens. 2002; 4(4):301-305.
  15. Tronvik E, et al.  Prophylactic Treatment of Migraine with an Angiotensin II Receptor Blocker, A Randomized Controlled Trial. JAMA. 2003; 289:65-69.
  16. Pitt B et al.  Randomized trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of  Losartan in the Elderly Study, ELITE).  Lancet. 1997; 349:747-52.
  17. Kalus JS, White CM.  Amlodipine vs Angiotensin-Receptor Blockers for Nonhypertension Indications. Ann Pharmacother. 2002 November; 2002; 36:1759-66.
  18. McClellan KJ & Balfour JA.  Eprosartan.  Drugs. 1998; 55(5): 713-718.
  19. Sever P, Holzgreve H.  Long-term efficacy and tolerability of candesartan cilexetil in patients with mild to moderate hypertension.  J Hum Hypertens. 1997; 11(Suppl 2): S69-S73.
  20. Packer M et al.  Consensus recommendations for the management of chronic heart failure.  Am J Cardiol. 1999; 83(2A): 1A-38A.
  21. Tenero D et al.  Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: Absolute bioavailability and effect of food.  Biopharm Drug Dispos. 1998; 19(6): 351-356.
  22. Argenziano L, Trimarco B.  Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: Subgroup analysis of a 26-week, double-blind, multicenter study.  Curr Med Res Opin 1999; 15(1): 9-14.
  23. Levine B.  Effect of eprosartan and enalapril in the treatment of black hypertensive patients: Subgroup analysis of a 26-week, double-blind, multicenter study.  Curr Med Res Opin 1999; 15(1): 25-32.
  24. Mckelvie R et al.  Comparison of candesartan, enalapril, and their combination in congestive heart failure: Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD pilot study).  Eur Hear J 1998; 19 (Suppl): 133.
  25. Song J. Review of Therapeutics, Pharmacologic, Pharmacokinetic and Therapeutic Differences Among Angiotensin II Receptor Antagonists. Pharmacotherapy. 2000;20(2):130-139.
  26. McMahon E.  Recent Studies with Eplerone, a Novel selective aldosterone receptor antagonist. Current Opinion in Pharmacology. 2001;1:190-196.
  27. Kaplan N. Should New Drugs Be Used Without Outcome Data?  Implications of the ALLHAT and ELITE II. Arch Intern. Med. 2001;161:511-512.
  28. Cohn JN, et al.  A Randomized Trial of the Angiotensin-Receptor Blocker Valsartan in Chronic Heart Failure Trial (Val-HeFT).  New Eng J Med. December 6, 2001; 245:1667-75.
  29. Thurmann PA, et al. Influence of the Angiotensin II Antagonist Valsartan on Left Ventricular Hypertrophy in Patients with Essential Hypertension. Circulation. 1998:2037-2042.
  30. Plum J, et al.  Effects of the Angiotensin II Antagonist Valsartan on Blood Pressure, Proteinuria, and Renal Hemodynamics in Patients with Chronic Renal Failure and Hypertension. J Am Soc Nephrol. 1998,9:2223-2234.
  31. Hedner T.  A Comparison of the Angiotensin II Antagonists Valsartan and Losartan in the Treatment of Essential Hypertension. AJH. April 1999;12(4):414-417.
  32. Fogari R et al.  Comparative Efficacy of Losartan and Valsartan in Mild-to-Moderate Hypertension:  Results of 24-Hour Ambulatory Blood Pressure Monitoring. Current Therapeutic Research. April 1999;60(4):195-205.
  33. Baruch L, et al.  Augmented Short and Long Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients with Heart Failure. Circulation. May 1999;99(20):2658-2664.
  34. Mazayev VP, et al. Valsartan in Heart Failure Patients Previously Untreated with an ACE Inhibitor. International Journal of Cardiology. 1998;65:239-246.
  35. Burnier M, Brunner HR. Comparative Antihypertensive Effects of Angiotensin II Receptor Antagonists.  Journal of the Amer. Society of Nephrology. April 1999, 10(Suppl 12):S278-S282.
  36. Carson PE. Rationale for the Use of Combination Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Therapy in Heart Failure. American Heart Journal. September 2000, 140(3).
  37. Martineua P, Goulet J.  New Competition in the Realm of Renin-Angiotensin Axis Inhibition; the Angiotensin II Receptor Antagonists in Congestive Heart Failure. Ann Pharmacother. 2001;35:71-84.
  38. Struckman DR, Rivey MP. Combined Therapy with an Antiotensin II Receptor Blocker and an Angiotensin-Converting Enzyme Inhibitor in Heart Failure. Ann Pharmacother.  2001;35:242-8.
  39. Gavras H.  Historical Evolution of Angiotensin II Receptor Blockers: Therapeutic Advantages. Journal of the American Society of Nephrology. April 1999;10(Suppl 12):S255-S257.
  40. Califf RM, Cohn JN.  Cardiac Protection: The Evolving Role of ARBS, Cardiac Protection: Evolving role of angiotensin receptor blockers. American Heart Journal. 2000 Jan;139(1 Pt 2):S15-22.
  41. Pfeffer MA.  Cardiac Protection: The Evolving Role of ARBs, Enhancing Cardiac Protection After Myocardial Infarction: Rationale for Newer Clinical Trials of Angiotensin Receptor Blockers. American Heart Journal. 2000 Jan;139(1 Pt 2):S23-8..
  42. Barbe SJ.  Comparison Between Angiotensin Receptor Antagonism and Converting Enzyme Inhibition in Heart Failure.  Differential Acute Effects According to the Renin-Angiotensin System Activation. Basic Res Cardiol. April 1999;94(2):128-35.
  43. Pfeffer MA, et al.  Valsartan in Acute Myocardial Infarction Trial (VALIANT). Am Heart J. 2000 Nov;140(5):727-50
  44. Konstam MA et al.  Effects of Losartan and captopril on Left Ventricular Volumes in Elderly Patients with Heart Failure: Results of the ELITE Ventricular Function Substudy. American Heart Journal. June 2000;39(6).
  45. Brenner BM, et al.  Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy. New Eng J Med. September 20, 2001;345:891-9.
  46. Miller AB, Srivastava P.  Angiotensin Receptor Blockers and Aldosterone Antagonists in Chronic Heart Failure. Cardiology Clinics. May 2001; 19(2).
  47. Palmieri V, et al.  Left Ventricular Function and Hemodynamic Features of Inappropriate Left Ventricular Hypertrophy in Patients with Systemic Hypertension; The LIFE Study. AHJ. May 2001;141(5).
  48. Granger CB, et al.  Clinical Investigations, Congestive Heart Failure, Randomized Trial of Candesartan cilexetil in the Treatment of Patients with Congestive Heart Failure and a History of Intolerance to Angiotensin-Converting Enzyme Inhibitors. AHJ. April 2000; 139(4).
  49. Kassler-Taub K, et al.  Comparative Efficacy of Two Angiotensin II Receptor Antagonists, Irbesartan and Losartan, in Mild to Moderate Hypertension. Amer J Hypertension. April 1998; 11:445-453.
  50. See S.  Angiotensin II Receptor Blockers for the Treatment of Hypertension. Expert Opin Pharmacother. November 2001; 2(11): 1795-804.
  51. Warnock DG.  Prevention, Protection, and the Intrarenal Renin-Angiotensin Systems. Semin Nephrol. November 1, 2001; 21(6):593-602.
  52. Gradman AH. Comparative Effects of Candesartan cilexetil and Losartan in Patients with Systemic Hypertension, Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group. Heart Dis. May-Jun 1999; 1(2):52-7.
  53. Kloner RA, Comparative Effects of Candesartan cilexetil and Amlodipine in Patients with Mild Systemic Hypertension.  Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators. Am J Cardiol. March 15, 2001;87(6):727-31.
  54. Elliott WJ.  Losartan Versus Valsartan in the Treatment of Patients with Mild to Moderate Essential Hypertension: Data from a Multicenter, randomized, double-blind, 12-week trial. Clin Ther.  August 1, 2001; 23(8):1166-79.
  55. Oparil S, et al.  Comparative Efficacy of Olmesartan, Losartan, Valsartan, and Irbesartan in the Control of Essential Hypertension. J Clin Hypertens. Sep/Oct 2001; 3(5):283-292.
  56. Ball K, et al.  A multi-center, double-blind, efficacy, tolerability and safety study of the oral angiotensin II-antagonist Olmesartan medoxomil versus losartan potassium in patients with mild to moderate essential hypertension (Study 866/19). J Hypertension. June 2001; 19(Suppl 1):S49-S56.
  57. Yusuf Salim.  From the HOPE to the ONTARGET and the TRANSCEND Studies: Challenges in Improving Prognosis. Am J Cardiol. January 24, 2002; 89(Suppl):18A-26A.
  58. Laeis P, Puchler K, Kirch W. The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction. J Hypertension. June 2001; 19(suppl 1):S21-S32.
  59. Dahlof B, et al.  Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. March 23, 2002; 359:995-1003.
  60. Lindholm LH, et al.  Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. March 23, 2002’ 359:1004-10.
  61. Mogensen CE, et al.  Randomised controlled trials of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. December 9, 2000; 321:1440-4.
  62. Jong P, et al.  Angiotensin Receptor Blockers in Heart Failure: Meta-Analysis of Randomized Controlled Trials. J Am Coll Cardiol. February 2, 2002; 39(3):463-70.
  63. Conlin PR, et al.  Angiotensin II Antagonists for Hypertension: Are There Differences in Efficacy?  Am J Hypertens. April 2000; 13(4, part 1), 418-426.
  64. Medical Economics, Inc., PDR Electronic Library. Thomson Medical Economics, Montvale, NJ; 2004.
  65. Fick DM, Cooper JW, Wade WE, et al.  Updating the Beers criteria for potentially inappropriate medication use in older adults.  Arch Intern Med. 2003;163:2716-24.
  66. Zahn C, Sangl J, Bierman AS, et al.  Potentially inappropriate medication use in the community-dwelling elderly.  JAMA.  2001;286:2823-29.
  67. AHFS Drug Information® with AHFSfirstReleases. (online from www.statref.com ), American Society Of Health-System Pharmacists, Bethesda, MD. 2005.
  68. DRUGDEX® System: Klasco RK (Ed):DRUGDEX® System. Online edition. Thomson Micromedex, Greenwood Village, CO.
  69. Drug Facts and Comparisons on-line. (www.drugfacts.com ), Wolters Kluwer Health, St. Louis, MO. 2006
  70. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003 Dec;42(6):1206-52.
  71. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004 May;43(5 Suppl 1):S1-290.
  72. 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.
Property of 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.

December 11, 2006
email this page   
Aetna
Skip Past Footer Links
Company Information   |   Site Map Aetna.com Home   |   Help   |   Contact Us   |   Search
Web Privacy Statement   |   Legal Statement   |   Privacy Notices   |   Member Disclosure

Back to top