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Beta-Blockers in Heart Failure Patients With Atrial Fibrillation: Do They Really Save Lives?

Article

A recent meta-analysis of beta-blocker use in patients with HF found that the drugs conferred no reduction in rates of mortality or hospitalization among patients with comorbid AF.

The development of heart failure (HF) in patients with atrial fibrillation (AF) is extremely common, with a prevalence that ranges from approximately 10% to 50%, depending on the severity of the HF and the assigned New York Heart Association Functional class.1-6 HF in patients with AF is the result of neurohormonal activation and mechanical stretch, among other factors, and is associated with an increased risk of stroke.7 Because of the proven mortality benefit of beta-blockers in HF patients,8-13 the findings of a recent study published in the Journal of American College of Cardiology – HeartFailure14 that cast doubt on their efficacy in HF/AF patients have become particularly relevant to clinical practice.

Current ACC/AHA guidelines for HF,15,16 which do not differentiate between patients with and without AF, recommend beta blockade to reduce morbidity and mortality. AF guidelines17,18 also recommend beta-blockers as first-line agents for rate control (not for mortality benefit) and especially for patients with comorbid HF-a “dual indication” for beta blockade. 

We are quickly learning, however, that all HF is not the same and that the effect of beta-blockers in patients with HF and AF is quite different from the effect in HF patients with normal sinus rhythm.

A recent meta-analysis from Reinstra and colleagues14 brought these differences to light. They included 4 randomized trials (CIBIS-II,12 MERIT-HF,19 SENIORS20) and the U.S. Carvedilol Trial11 of beta-blockers in patients with HF (ejection fraction less than 40%). These trials covered the 4 currently approved beta-blockers for HF (bisoprolol, metoprolol extended-release, nevibolol, and carvedilol, respectively), and included a total of 8680 patients. After adjustment for confounding variables, beta blockade was not associated with a reduction in mortality across all patients (odds ratio [OR]=0.86; P=.28); in sinus-rhythm patients, however, there was a significantly lower mortality rate (OR=0.63; P<.0001). Furthermore, beta-blocker use was not associated with a reduction in HF hospitalizations in AF (OR=1.11; P=.44), whereas in patients experiencing sinus rhythm, a lower rate was observed (OR=0.58; P<.0001).

So we now stand at a difficult crossroads. Should we be taking patients with HF and AF off beta-blockers? Although this study was well conducted and included a large population, it would be premature to conclude that all patients with HF and AF should not be treated with a beta-blocker. Additional randomized studies are needed to definitely establish this. There are differences among beta-blockers, as well, and some (eg, bucindolol) have proved beneficial in comorbid HF and AF. It is becoming increasingly apparent, however, that HF is heterogeneous and that management should be individually tailored. 

So, the next time there is a patient in your clinic with AF and HF who cannot tolerate a beta-blocker, it may be worth a discussion with his or her cardiologist about whether the therapy can be safely discontinued.
 

References:
1. Carson PE, Johnson GR, Dunkman WB, et al. The influence of atrial fibrillation on prognosis in mild to moderate heart failure. The V-Heft studies. The V-Heft Va Cooperative Studies Group. Circulation. 1993;87(6 Suppl):VI102-V110.
2. Stevenson WG, Stevenson LW, Middlekauff HR, et al. Improving survival for patients wit hatrial fibrillation and advanced heart failure. J Am Coll Cardiol. 1996;28:1458-1463.
3. Dries DL, Exner DV, Gersh BJ, et al. Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the Solvd Trials. Studies of Left Ventricular Dysfunction. J Am Coll Cardiol. 1998;32:695-703.
4. Joglar JA, Acusta AP, Shusterman NH, et al. Effect of carvedilol on survival and hemodynamics in patients with atrial fibrillation and left ventricular dysnfunction: retrospective analysis of the US Carvedilol Heart Failure Trials Program. Am Heart J. 2001;142:498-501.
5. Mahoney P, Kimmel S, DeNofrio D, et al. Prognostic significance of atrial fibrillation in patients at a tertiary medical center referred for heart transplantation because of severe heart failure. Am J Cardiol. 1999;83:1544-1547.
6. Maisel WH, Stevenson LW. Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol. 2003;91:2D-8D.
7. Middlekauff HR, Stevenson WG, Stevenson LW. Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients. Circulation. 1991;84:40-48.
8. Packer M, Colucci WS, Sackner-Bernstein JD, et al. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The Precise Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise. Circulation. 1996;94:2793-2799.
9. Lechat P, Packer M, Chalon S, et al. Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation. 1998;98:1184-1191.
10. Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Mocha Investigators. Circulation. 1996;94:2807-2816.
11. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349-1355.
12. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9-13.
13. Exner DV, Dries DL, Waclawiw MA, et al. Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the studies of left ventricular dysfunction. J Am Coll Cardiol. 1999;33:916-923.
14. Rienstra M, Damman K, Mulder BA, et al. Beta-blockers and outcome in heart failure and atrial fibrillation: a meta-analysis. JACC Heart Failure. 2013;1(1):7.
15. Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119:1977-2016.
16. 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 (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005;112:e154-e235.
17. Fuster V, Rydn LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011;123:e269-e367.
18. Fuster V, Rydn LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257-e354.
19. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001-2007.
20. van Veldhuisen DJ, Cohen-Solal A, Bohm M, et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure). J Am Coll Cardiol. 2009;53:2150-2158.

 

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