Vol 26, No 6 (2019)
Original articles — Clinical cardiology
Published online: 2018-07-13

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The effect of beta-blockers on mortality in patients with heart failure and atrial fibrillation: A meta-analysis of observational cohort and randomized controlled studies

Gai-gai Ma1, Quan Fang1, Feng-xia Wang2
Pubmed: 30009373
Cardiol J 2019;26(6):744-752.


Background: Beta-blockers (BB) are the cornerstone of therapy for heart failure (HF); however, the
effects of these drugs on the prognosis of patients with concomitant atrial fibrillation (AF) remain
controversial. The objective of this meta-analysis was to evaluate the efficacy of BB on mortality in HF
coexisting with AF.
Methods: A systematic search of PubMed, Embase and the Cochrane Library databases was
conducted. Observational cohort studies and randomized controlled trials reporting outcomes of
mortality or HF hospitalizations for patients with HF and AF, being assigned to BB treatment.
A non-BB group was also included.
Results: A total of 8 clinical studies (5 randomized controlled trials and 3 observational cohort studies)
involving 34197 patients were included in the analysis. The pooled analysis demonstrated that BB
treatment was associated with a 22% reduction in relative risk of all-cause mortality in patients with
HF and AF (RR: 0.78; 95% CI 0.71–0.86; p < 0.00001; I2 = 27%). The pooled analysis of 5 studies
reported the outcome of HF hospitalization (2774 patients) which showed that BB therapy was not associated
with a reduction of HF hospitalizations (RR: 0.94; 95% CI 0.79–1.11; p = 0.46; I2 = 38%).
Conclusions: Meta-analysis suggests the potential mortality benefit of BB in patients with HF and AF.
It was concluded herein that it is premature to deny patients with AF and HF to receive BB therapy
considering current evidence.

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  1. Benjamin EJ, Blaha MJ, Chiuve SE, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017; 135(10): e146–e603.
  2. Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013; 6(3): 606–619.
  3. Krijthe BP, Kunst A, Benjamin EJ, et al. Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur Heart J. 2013; 34(35): 2746–2751.
  4. Olsson LG, Swedberg K, Ducharme A, et al. Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program. J Am Coll Cardiol. 2006; 47(10): 1997–2004.
  5. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014; 130(23): 2071–2104.
  6. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016; 37(38): 2893–2962.
  7. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37(27): 2129–2200.
  8. Yancy C, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017; 136(6): e137–e161.
  9. Joglar JA, Acusta AP, Shusterman NH, et al. Effect of carvedilol on survival and hemodynamics in patients with atrial fibrillation and left ventricular dysfunction: retrospective analysis of the US Carvedilol Heart Failure Trials Program. Am Heart J. 2001; 142(3): 498–501.
  10. Lechat P, Hulot JS, Escolano S, et al. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation. 2001; 103(10): 1428–1433.
  11. Mulder BA, van Veldhuisen DJ, Crijns HJ, et al. Effect of nebivolol on outcome in elderly patients with heart failure and atrial fibrillation: insights from SENIORS. Eur J Heart Fail. 2012; 14(10): 1171–1178.
  12. van Veldhuisen DJ, Aass H, El Allaf D, et al. MERIT-HF Study Group. Presence and development of atrial fibrillation in chronic heart failure. Experiences from the MERIT-HF Study. Eur J Heart Fail. 2006; 8(5): 539–546.
  13. Kao DP, Davis G, Aleong R, et al. Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation. Eur J Heart Fail. 2013; 15(3): 324–333.
  14. Rienstra M, Damman K, Mulder BA, et al. Beta-blockers and outcome in heart failure and atrial fibrillation: a meta-analysis. JACC Heart Fail. 2013; 1(1): 21–28.
  15. Kotecha D, Holmes J, Krum H, et al. Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014; 384(9961): 2235–2243.
  16. Nielsen PB, Larsen TB, Gorst-Rasmussen A, et al. β-Blockers in atrial fibrillation patients with or without heart failure: association with mortality in a nationwide cohort study. Circ Heart Fail. 2016; 9(2): e002597.
  17. Cadrin-Tourigny J, Shohoudi A, Roy D, et al. Decreased Mortality With Beta-Blockers in Patients With Heart Failure and Coexisting Atrial Fibrillation: An AF-CHF Substudy. JACC Heart Fail. 2017; 5(2): 99–106.
  18. Li SJ, Sartipy U, Lund LH, et al. Prognostic Significance of Resting Heart Rate and Use of β-Blockers in Atrial Fibrillation and Sinus Rhythm in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Swedish Heart Failure Registry. Circ Heart Fail. 2015; 8(5): 871–879.
  19. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996; 17(1): 1–12.
  20. Scheen AJ, Ernest P, Jandrain B. [How I explore ... a risk difference in the occurrence of an event in clinical trials]. Rev Med Liege. 2012; 67(11): 597–602.
  21. Pan An, Sun Qi, Okereke OI, et al. Depression and risk of stroke morbidity and mortality: a meta-analysis and systematic review. JAMA. 2011; 306(11): 1241–1249.
  22. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11): 1539–1558.
  23. DerSimonian R, Laird N. Meta-analysis in clinical trials revisited. Contemp Clin Trials. 2015; 45(Pt A): 139–145.
  24. Simpson J, Castagno D, Doughty RN, et al. Is heart rate a risk marker in patients with chronic heart failure and concomitant atrial fibrillation? Results from the MAGGIC meta-analysis. Eur J Heart Fail. 2015; 17(11): 1182–1191.
  25. Wan H, Yang Y, Zhu J, et al. Prognostic value of ventricular heart rate in patients with permanent atrial fibrillation and heart failure. Int J Cardiol. 2015; 182: 70–71.
  26. Cullington D, Goode KM, Zhang J, et al. Is heart rate important for patients with heart failure in atrial fibrillation? JACC Heart Fail. 2014; 2(3): 213–220.
  27. Miller RJH, Howlett JG, Chiu MH, et al. Relationships among achieved heart rate, β-blocker dose and long-term outcomes in patients with heart failure with atrial fibrillation. Open Heart. 2016; 3(2): e000520.
  28. Groenveld HF, Tijssen JGP, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010; 362(15): 1363–1373.
  29. Mulder BA, Van Veldhuisen DJ, Crijns HJ, et al. Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post-hoc analysis of the RACE II study. Eur J Heart Fail. 2013; 15(11): 1311–1318.