Association between use of β-blockers and outcomes in patients with heart failure and preserved ejection fraction.

 
Lund LH, Benson L, Dahlström U, et al.
JAMA. 2014 Nov 19;312(19):2008-18. doi: 10.1001/jama.2014.15241
 

Background

Mortality in patients with heart failure with preserved ejection fraction (HFpEF) may be as high as in HF with reduced EF (HFrEF), but no proven therapy is available. HFpEF and HFrEF share numerous pathophysiological mechanisms, and signs and symptoms. Beta-blockers improve outcomes in HFrEF [1]. They may also be beneficial in HFpEF by lowering blood pressure and reducing left ventricular hypertrophy [2] and diastolic dysfunction [3] and by slowing heart rate and reducing myocardial oxygen demand.
Data on beta-blocker use in HFpEF have yielded inconclusive results thus far, and beta-blockers are currently not indicated for treatment of HFpEF [4,5]. This study tested the hypothesis that beta-blockers are associated with reduced mortality in HFpEF. To this extent, data from patients with HF in the Swedish Heart Failure Registry [6] were used. 19083 individual patients with HFpEF were included in the main analysis, of whom 15786 were treated with beta-blockers and 3297 were not. After 2:1 propensity matching, data of 5496 treated and 2748 un-treated were analysed.
 

Main results

• In the overall HFpEF cohort (median follow-up time: 755 days), among those who received beta-blockers, the total number of deaths was 5639 (36%) vs. 1518 (46%) in those not on beta-blockers (143 deaths/1000 patient-years (PY) with beta-blockers vs. 198/1000 PY).
• Survival at 1 year was 84% (95%CI: 83-85%) with beta-blockers, vs. 78% (95%CI: 76-69%) among those without. Survival at 5 years was 51% (95%CI: 50-52%) with and 41% (95%CI: 39-44%) without beta-blockers. Unadjusted HR throughout follow-up was: 0.73 (95%CI: 0.69-0.77, P<0.001).
• In the matched cohort (median follow-up time: 709 days), 2279 (41%) of those who received beta-blockers died, vs. 1244 (45%) of those who did not (177/1000 PY with beta-blockers vs. 191/1000 PY, P=0.03).
• After 1 year, survival was 80% (95%CI: 79-81%) for those on beta-blockers, vs. 79% (95%CI: 78-81%) not on beta-blockers. After 5 years, 45% (95%CI:43-47%) on beta-blockers had survived, vs. 42% (95%CI:40-45%) among those who did not. HR throughout follow-up was 0.93 (95%CI:0.86-0.996, P=0.04).
• In the matched cohort, survival free from HF hospitalisation at 1 year was 58% (95%CI:57-59%) on beta-blockers vs. 59% (95%CI: 57-61%), with an HR throughout follow-up of 0.98 (95%CI:0.92-1.04, P=0.46).
• A positive control analysis in matched HFrEF patients showed survival at 1 year of 78% (95%CI: 76-79%) in treated vs. 75% (95%CI: 73-77%) in untreated patients, with an HR throughout follow-up of 0.89 (95%CI: 0.82-0.97, P=0.005). Beta-blocker use was also associated with a similarly reduced HR for HF hospitalisation or mortality.

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Conclusion

This large prospective propensity score-matched registry analysis of unselected patients with HFpEF, showed that beta-blockers were associated with reduced all-cause mortality. Treatment with beta-blockers were, however, not associated with lower all-cause mortality or hospitalisation for HF.  Sufficiently powered randomised controlled trials can give further answers on the use of beta-blockers in HFpEF.
 
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References

1. Brophy JM, Joseph L, Rouleau JL. Beta-blockers in congestive heart failure: a Bayesian meta-analysis. Ann Intern Med. 2001;134(7):550-560.
2. Klingbeil AU, Schneider M, Martus P, et al. Ameta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med. 2003;115(1):41-46.
3. Bergstrom A, Andersson B, Edner M, et al. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function: results of the Swedish Doppler- echocardiographic study (SWEDIC). Eur J Heart Fail. 2004;6(4):453-461.
4. McMurray JJ, Adamopoulos S, Anker SD, et al; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for
the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787-1847.
5. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation.  2013;128(16):1810-1852.
6. Lund LH, Benson L, Dahlstrom U, Edner M. Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction. JAMA. 2012;308(20):2108-2117.