Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: An individual patient-level analysis of double-blind randomized trials

John G F Cleland, Karina V Bunting, Marcus D Flather, Douglas G Altman, Jane Holmes, Andrew J S Coats, Luis Manzano, John J V McMurray, Frank Ruschitzka, Dirk J. van Veldhuisen, Thomas G Von Lueder, Michael Böhm, Bert Andersson, John Kjekshus, Milton Packer, Alan S Rigby, Giuseppe Rosano, Hans Wedel, Åke Hjalmarson, John WikstrandDipak Kotecha

Research output: Contribution to journalArticlepeer-review

201 Citations (Scopus)
23 Downloads (Pure)

Abstract

Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. 

Methods and results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. 

Conclusion: Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%. 

Original languageEnglish
Pages (from-to)26–35
Number of pages10
JournalEuropean Heart Journal
Volume39
Issue number1
Early online date10 Oct 2017
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Heart failure
  • Ejection fraction
  • Beta-blockers
  • Mortality
  • Sinus rhythm
  • Atrial fibrillation

Cite this