Elsevier

JACC: Heart Failure

Volume 3, Issue 8, August 2015, Pages 603-614
JACC: Heart Failure

Mini-Focus Issue: Global Health
Original Research
Falling Cardiovascular Mortality in Heart Failure With Reduced Ejection Fraction and Implications for Clinical Trials

https://doi.org/10.1016/j.jchf.2015.03.013Get rights and content
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Abstract

Objectives

This study examined the trends in the relative contributions of cardiovascular and noncardiovascular mortality to total mortality according to use of beta-blockers in clinical trials of patients with heart failure with reduced ejection fraction (HF-REF).

Background

With the increasingly widespread use of disease-modifying therapies, particularly beta-blockers, in HF-REF, the proportion of patients dying from cardiovascular causes is likely to be decreasing.

Methods

In a systematic review, 2 investigators independently searched online databases to identify clinical trials including >400 patients with chronic heart failure published between 1986 and 2014 and that adjudicated cause of death. Trials were divided into 3 groups on the basis of the proportion of patients treated with a beta-blocker (<33% [low], 33% to 66% [medium], and >66% [high]). Percentages of total deaths adjudicated as cardiovascular or noncardiovascular were calculated by weighted means and weighted standard deviations. Weighted Student t tests were used to compare results between groups.

Results

Sixty-six trials met the inclusion criteria with a total of 136,182 patients and 32,140 deaths. There was a sequential increase in the percentage of noncardiovascular deaths with increasing beta-blocker use from 11.4% of all deaths in trials with low beta-blocker use to 19.1% in those with high beta-blocker use (p < 0.001).

Conclusions

In trials of patients with HF-REF, the proportion of deaths adjudicated as cardiovascular has decreased. Cardiovascular mortality, and not all-cause mortality, should be used as an endpoint for trials of new treatments for HF-REF.

Key Words

beta-blocker
cause of death
heart failure
heart failure with reduced ejection fraction
mode of death

Abbreviations and Acronyms

ACEI
angiotensin-converting enzyme inhibitor
ARB
angiotensin receptor blocker
BB
beta blocker
CV
cardiovascular
HF
heart failure
HF-PEF
heart failure with preserved ejection fraction
HF-REF
heart failure with reduced ejection fraction
NYHA
New York Heart Association
RCT
randomized controlled trial

Cited by (0)

Dr. Campbell is supported by a British Heart Foundation Project Grant, number PG/13/17/30050. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Rush and Campbell contributed equally to this work.