Differences in ejection fraction as inclusion criterion in randomized controlled trials among patients with heart failure with reduced ejection fraction: a systematic review

ABSTRACT

Introduction

Heart failure (HF) with reduced ejection fraction (HFrEF) has been defined by varying ejection fraction (EF) criteria in clinical trials, leading to differences in quantifying treatment effects.

Areas covered

The definitions of HFrEF in randomized controlled trials from 2010 until 2020 were collected. The EF ranges were clustered into very low (<30%), low (30–39%) and mildly reduced (40–49%) stratified by intervention. A time series regression analysis was performed. A total of 3052 articles were screened and 706 were included. Interventions included were pharmacologic (37%), device therapy (10%), and a combination of programs, procedural, and laboratory testing (53%). Regarding EF cutoffs, 41% of the studies utilized <40% while 26% used <35%. About 31% did not have a clearly defined EF. Between 2010 and 2020, studies with HFrEF ranges 30–39% have significantly decreased (p value < 0.001 for trend), but those which included very low EF (<30%) and mildly reduced EF (40–49%) have remained the same.

Expert opinion

EF definitions across clinical trials in HFrEF varied widely. Defining the specific target HF population phenotype when designing trials or in patient treatment is important as various beneficial effects of different heart failure treatment modalities can be modified or even attenuated across the spectrum of EF.

KEYWORDS:

• Differences in ejection fraction
• Randomized clinical trials
• HFrEF
• Systematic review

Article highlights

• EF definitions used across clinical trials in HFrEF varied widely.

• Almost a third of randomized controlled trials in HFrEF did not have a clearly defined EF.

• The most commonly used definition for HFrEF is <40% in accordance with the prevailing guidelines.

• In the last decade, studies of HFrEF with EF ranges 30–39% have significantly decreased (p value<0.001 for trend), but those which included very low EF (<30%) and mildly reduced EF (40–49%) have remained essentially the same.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.