Subject: Beta-Adrenergic Blocking Agents

Status	Drug	PR	PR-QL	PR-AL	ST	M EX‡
P	acebutolol
P	atenolol
P	atenolol/chlorthalidone
P	betaxolol
P	bisoprolol
P	carvedilol
P	metoprolol
P	Metoprolol/hydrochlorothiazide
P	nadolol
P	nadolol/ bendroflumethiazide
P	pindolol
P	propranolol
P	timolol
P	bisoprolol/hydrochlorothiazide
P	Bystolic®  (nebivolol HCl)
P	Coreg®  (carvedilol)				X
P	Coreg CR®  (carvedilol sr)
NP	Tenoretic®  (atenolol/chlorthalidone)
NP	Inderide®  (propranolol/hydrochlorothiazide)
FE	Cartrol®  (carteolol)					X
FE	Corzide®  (nadolol/ bendroflumethiazide)					X
FE	Kerlone®  (betaxolol)					X
FE	Levatol®  (penbutolol)					X
FE	Lopress® HCT ®  (metoprolol/hydrochlorothiazide)					X
FE	metoprolol SR					X
FE	Timolide®  (timolol/ hydrochlorothiazide)					X
FE	Toprol XL®  (metoprolol SR)					X
FE	Zebeta®  (bisoprolol)					X

Policy:

 

1. Precertification Criteria
 


 

2. Step Therapy Criteria

Under some plans, including plans that use an open or closed formulary,  Coreg is subject to step-therapy.  Aetna considers Coreg to be medically necessary for those members who meet the following step-therapy criteria:

 

For Coreg

A documented trial of one month of the preferred generic equivalent carvedilol

 

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. (see criteria under section II below.)


 

3. Medical Exception Criteria

Cartrol, Corzide, Kerlone, Levatol,  Lopress HCT, metoprolol sr, Timolide, Toprol XL and Zebeta are currently listed on the Aetna Formulary Exclusions List.* 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 Cartrol, Corzide, Kerlone,  Levatol, Lopress HCT, metoprolol sr, Timolide, Toprol XL and Zebeta to be medically necessary for those members who meet the criteria as specified below:

 

Coreg is  currently listed on the Aetna Step-Therapy List.* Therefore, Coreg is excluded from coverage for members enrolled in prescription drug benefit plans that require step-therapy criteria, unless a medical exception is granted.  Aetna considers Coreg to be medically necessary for those members who meet the following criteria

 

For Corzide, Lopress HCT, Timolide:

A.   A documented:

§         Contraindication to two preferred alternatives, one of which was a beta blocker/diuretic combination, indicated for the member's condition OR

§         Intolerance to two preferred alternatives, one of which was a beta blocker/diuretic combination, indicated for the member's condition OR

§         Allergy to two preferred alternatives, one of which was a beta blocker/diuretic combination, indicated for the member's condition OR

§         Failure of an adequate trial of one month each of at least two preferred alternatives, one of which was a beta blocker/diuretic combination, indicated for the member's condition.

 For Cartrol, Kerlone, Levatol, metoprolol sr, Toprol XL and Zebeta:

A.      A documented:

§         Intolerance to two preferred alternatives indicated for the member's condition OR

§         Contraindication to two preferred alternatives indicated for the member's condition OR

§         Allergy to two preferred alternatives indicated for the member's condition OR

§         Failure of an adequate trial of one month each of two preferred alternatives indicated for the member's condition.

 

OR

 

B.     Member is documented to be currently stabilized on respective drug, Cartrol, Kerlone, Levatol, or Zebeta.

 

For Coreg,

A.     Member has a documented:

§         Contraindication to the preferred generic equivalent carvedilol OR

§         Intolerance to the preferred generic equivalent carvedilol  OR

§         Allergy to the preferred generic equivalent carvedilol OR

§         Failure of an adequate trial of one month of the preferred generic equivalent carvedilol

 

Special Notes:

 

Place of Service:

Outpatient

The above policy is based on the following references:

1. DrugPoints® System ( www.statref.com) Thomson Micromedex, Greenwood Village, CO. Updated periodically.
2. AHFS Drug Information® with AHFSfirstReleases®. ( www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. Updated periodically.
3. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
4. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. Updated periodically.
5. PDR® Electronic Library™ [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
6. The CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left ventricular dysfunction: the CAPRICORN randomized trial. Lancet 2001; 357: 1385-1390.
7. Hunt SA, Abraham WT, Chin MH, et al. 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 [trunc]. Bethesda (MD): American College of Cardiology Foundation (ACCF). J Am Coll Cardiol. 2005;46:1116-43.
8. Anderson JL, Adams CD, Antman EM, et al. American College of Cardiology, American Heart Association Task Force on Practice Guidelines (Writing Committee, American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, American Association of Cardiovascular and Pulmonary Rehabilitation, Society for Academic Emergency Medicine. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology. J Am Coll Cardiol 2007 Aug 14;50(7):e1-e157.
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26. Heidenreich PA, Lee TT, Massie BM. Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials.  J Am Coll Cardiol. 1997;30:27-34.
27. Dargie, H, for The CAPRICORN Investigator, Effect of Carvedilol on Outcome After Myocardial Infarction in Patients with Left-Ventricular Dysfunction: The CAPRICORN Randomized Trial, Lancet, 2001; 357:1385-90.
28. Krum H. Roecker E. Mohacsi P et al. Effects of initiating carvedilol in patients with severe chronic heart failure. Results from the COPERNICUS study. JAMA 2003; 289: 712-718.
29. Poole-Wilson PA, Swedberg K, Cleland JG, et al; Carvedilol Or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomized controlled trial. Lancet. 2003 Jul 5;362(9377):7-13.
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32. CIBIS Investigators and Committees. A randomized trial of beta-blockade in heart failure: The Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation. 1994;90:1765-73.
33. Australia-New Zealand Heart Failure Research collaborative Group.  Effects of carvedilol, a vasodilator- -blocker, in patients with congestive heart failure due to ischaemic heart disease.  Circulation. 1995;92:212-8.
34. Australia-New Zealand Heart Failure Research Collaborative Group.  Randomized, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease.  Lancet. 1997;349:375-80.
35. CIBIS-II Investigators and committees.  The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomized trial.  Lancet. 1999;353:9-13.
36. MERIT-HF Study Group.  Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF).  Lancet. 1999;353:2001-6.
37. Heidenreich PA, McDonald KM, Hastie T, et al. Meta-analysis of trials comparing beta-blockers, calcium antagonist, and nitrates for stable angina. JAMA 1999;281:1927-36.
38. Savonitto S, Ardissiono D, Egstrup K. J Am Coll Cardiol. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study. 1996;27(2):311-6.
39. von Arnim T. Medical treatment to reduce total ischemic burden: total ischemic burden bisoprolol study (TIBBS), a multicenter trial comparing bisoprolol and nifedipine. The TIBBS Investigators. J Am Coll Cardiol. 1995 Jan;25(1):231-8.
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41. Fauchier L, Pierre B, de Labriolle A, Babuty D. Comparison of the beneficial effect of beta-blockers on mortality in patients with ischaemic or non-ischaemic systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2007;9(11):1136-9.
42. 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee. Circulation. 2008 Jan 15;117(2):296-329.
43. Flather MD, Shibata MC, Coats AJS, et al on behalf of the SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005;26:215-225.
44. Bradley HA, Wiysonge CS, Volmink JA, et al. How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis. J Hypertens. 2006;24(11):2131-41.
45. Fardoun RZ. Carvedilol versus cardioselective beta-blockers for the treatment of hypertension in patients with type 2 diabetes mellitus. Pharmacotherapy 2006;26(10):1491-500.
46. Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352:1861-72.
47. Weiss RJ, Weber MA, Carr AA, Sullivan WA, et al. A randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of nebivolol, a novel beta-blocker, I patients with mild to moderate hypertension. J Clin Hypertens. 2007;9:667-676.
48. Saunders E, Smith WB, DeSalvo KB, Sullivan WA. The efficacy and tolerability of nebivolol in hypertensive African American patients. J Clin Hypertens. 2007;9:866-875.
49. Bangalore S, Parkar S, Grossman E, Messerli FH. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus. Am J Cardiol. 2007 Oct 15;100(8):1254-62.
50. Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002252.
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52. Nasr IA, Bouzamondo A, Hulot JS, et al. Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis. Eur Heart J. 2007 Feb;28(4):457-62.
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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.

August 01, 2008