Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials. (10th October 2017)

• Record Type: Journal Article
• Authors: Cleland, John G F; Bunting, Karina V; Flather, Marcus D; Altman, Douglas G; Holmes, Jane; Coats, Andrew J S; Manzano, Luis; McMurray, John J V; Ruschitzka, Frank; van Veldhuisen, Dirk J; von Lueder, Thomas G; Böhm, Michael; Andersson, Bert; Kjekshus, John; Packer, Milton; Rigby, Alan S; Rosano, Giuseppe; Wedel, Hans; Hjalmarson, Åke; Wikstrand, John; Kotecha, Dipak
• Is Part Of: European heart journal. Volume 39:Number 1(2018)
• Page Start: 26
• Page End: 35
• Publication Date: 2017-10-10
• Subjects: Heart failure -- Ejection fraction -- Beta-blockers -- Mortality -- Sinus rhythm -- Atrial fibrillation; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehx564
• Languages: English
• ISSNs: 0195-668X

Abstract

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%.