Beta-blockers reduce mortality in HFrEF with sinus rhythm

Beta-blockers reduced mortality in individuals with HF with reduced ejection fraction in sinus rhythm regardless of pretreatment heart rate, according to findings presented at Heart Failure 2017 in Paris.

“Beta-blockers reduce morbidity and mortality in patients with [HFrEF] in sinus rhythm,” Dipak Kotecha, PhD, of the Institute of Cardiovascular Sciences at the University of Birmingham, United Kingdom, and the Centre of Cardiovascular Research and Education in Therapeutics at Monash University, Australia, and colleagues wrote in a simultaneous publication in the Journal of the American College of Cardiology. “It is not clear whether the key mechanism underpinning their benefits is protection of adrenergic receptors from heightened sympathetic activity or reduction in heart rate. It is also uncertain whether the efficacy of beta-blockers is related to dose, reduction in heart rate or achieved heart rate. These questions are conceptually important for how clinicians manage and follow-up patients with HFrEF.”

Kotecha and colleagues performed a meta-analysis of data from 11 double blind, randomized controlled trials of beta-blockers in participants with HFrEF in either sinus rhythm or atrial fibrillation (median age, 65 years; 24% women; median left ventricular EF at baseline, 27%). The primary outcome was all-cause mortality.

In participants in sinus rhythm (n = 14,166), higher heart rate at baseline was associated with a greater all-cause mortality (adjusted HR = 1.11 per 10 beats per minute; 95% CI, 1.07-1.15) after mean follow-up of 1.5 years. This association was not found in participants with AF (n = 3,034; HR = 1.03 per 10 beats per minute; 95% CI, 0.97-1.08).

In participants randomly assigned to beta-blockers, ventricular rate was reduced by 12 beats per minute regardless of whether they were in sinus rhythm or AF.

Participants in sinus rhythm randomly assigned to beta-blockers had a lower risk for mortality (HR = 0.73; 95% CI, 0.67-0.79) vs. placebo, regardless of baseline heart rate (P for interaction = .35). Beta-blockers did not affect mortality in participants with AF (HR = 0.95; 95% CI, 0.81-1.12) at any heart rate (P for interaction = .48).

In participants with sinus rhythm, but not AF, achieving a lower heart rate, irrespective of treatment, was associated with better prognosis (HR = 1.16 per 10 beats per minute; 95% CI, 1.11-1.22).

“Our analysis confirms a reduction in mortality with beta-blockers for patients with HFrEF in sinus rhythm, irrespective of pretreatment heart rate within the studied range,” the researchers wrote. “Resting heart rate is an important prognostic indicator, both before and after initiation of beta-blockers; a lower achieved heart rate is associated with lower subsequent mortality and is more likely to occur in patients initiated on a beta-blocker. In patients with concomitant AF, heart rate was not associated with mortality and beta-blockers did not reduce mortality at any observed heart rate.” – by Cassie Homer

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Reference:

Kotecha D, et al. Heart Failure Patients with Comorbidities. Presented at: Heart Failure 2017 and the 4th World Congress on Acute Heart Failure; April 29-May 2, 2017; Paris.

Kotecha D, et al. J Am Coll Cardiol. 2017;doi:10.1016/j.jacc.2017.04.001.

Disclosure: Kotecha reports receiving grants from Menarini, nonfinancial support from Daiichi Sankyo and personal fees from AtriCure. Please see the full study for a list of the other researchers’ relevant disclosures.