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Sex-specific differences in the efficacy of heart failure therapies: a meta-analysis of 84,818 patients

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Abstract

Women have been historically underrepresented in clinical trials of heart failure (HF). We aimed to assess for sex differences in patient characteristics and the efficacy of guideline-directed medical therapy (GDMT) in HF. Systematic literature search for randomized controlled trials (RCTs) of GDMT reporting cardiovascular outcomes by sex in patients with HF. The primary outcome was the composite of cardiovascular death and hospitalization for HF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using inverse variance weighting and random effects meta-analysis. Twenty-six RCTs totaling 84,818 participants (27% women) were included. Women with HF were older, had higher New York Heart Association (NYHA) class, more hypertension and obesity, and higher mean left ventricular ejection fraction compared to men. There was evidence for most GDMT in reducing the primary outcome in women with HF with reduced ejection fraction (HFrEF) (angiotensin-converting enzyme inhibitors/angiotensin-receptor blocker [RR 0.86, 95% CI 0.75–0.97], angiotensin-receptor blocker/neprilysin inhibitor (ARNI) [RR 0.77, 95% CI 0.62–0.94], beta-blocker [RR 0.67, 95% CI 0.51–0.89], ivabradine [RR 0.74, 95% CI 0.60–0.91], and sodium-glucose cotransporter-2 (SGLT2) inhibitors [RR 0.66, 95% CI 0.54–0.81]) and a non-significant trend for benefit with mineralocorticoid-receptor-antagonist (MRA) [RR 0.77, 95% CI 0.52–1.16]). Compared to men with HFrEF, GDMT reduced the primary outcome in women to a similar degree across all drug classes (ratio of RR 1.05, 95% CI 0.96–1.14). Despite differences in baseline characteristics and an underrepresentation of women in HF clinical trials, GDMT are as efficacious in women as compared to men in reducing cardiovascular events in HF.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. The George Institute for Global Health, UNSW, Sydney, Australia

    Nelson Wang

  2. Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Nelson Wang, Sonia Sawant, James Sindone & Sean Lal

  3. St. Vincent’s Hospital, Sydney, Australia

    Jack Evans

  4. Sydney Medical School, University of Sydney, Sydney, Australia

    Nelson Wang & Sean Lal

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NW contributed to study conception and design. Material preparation, data collection, and analysis were performed by NW, JE, SS, and JS. The first draft of the manuscript was written by NW, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Nelson Wang.

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Wang, N., Evans, J., Sawant, S. et al. Sex-specific differences in the efficacy of heart failure therapies: a meta-analysis of 84,818 patients. Heart Fail Rev 28, 949–959 (2023). https://doi.org/10.1007/s10741-022-10275-1

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