Falling cardiovascular mortality in heart failure with reduced ejection fraction and implications for clinical trials

Rush, C. J., Campbell, R. T., Jhund, P. S. , Connolly, E. C., Preiss, D. , Gardner, R. S., Petrie, M. C. and McMurray, J. J.V. (2015) Falling cardiovascular mortality in heart failure with reduced ejection fraction and implications for clinical trials. JACC: Heart Failure, 3(8), pp. 603-614. (doi:10.1016/j.jchf.2015.03.013) (PMID:26251086)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Preiss, Dr David and Jhund, Dr Pardeep and Petrie, Professor Mark and Gardner, Professor Roy and Connolly, Dr Eugene and Campbell, Dr Ross and McMurray, Professor John and Rush, Dr Christopher
Authors: Rush, C. J., Campbell, R. T., Jhund, P. S., Connolly, E. C., Preiss, D., Gardner, R. S., Petrie, M. C., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:JACC: Heart Failure
Publisher:Elsevier
ISSN:2213-1779
ISSN (Online):2213-1787

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
615391Palliative Care Needs in Patients with Heart FailureJohn McMurrayBritish Heart Foundation (BHF)PG/13/17/30050RI CARDIOVASCULAR & MEDICAL SCIENCES