Sex-Based Differences in Chronic Heart Failure: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Authors

Luca Fazzini, Luca Pascalis, Cristina Madaudo, Giordano Maria Pugliesi, Paolo Manca, Vincenzo Nuzzi, Gregorio Tersalvi, Emilia D'Elia, Christian Cadeddu Dessalvi, Roberta Montisci, Mauro Gori, Michele Senni, Antonio Cannatà

Published in

European journal of heart failure. Oct 15, 2026. Epub Oct 15, 2026.

Abstract

Sex-based disparities in patient enrollment and treatment effects in heart failure (HF) randomized controlled trials (RCTs) have been reported. We aim to systematically analyze sex-based enrollment and treatment effect differences in HF RCTs over time.
RCTs enrolling patients with chronic HF were systematically searched on PubMed-MEDLINE. Eligible trials included pharmacological or device-based interventions with a hard primary endpoint (mortality and hospitalization) and reporting enrollment of women. Sex-specific treatment effects (HR or RR) were extracted. Meta-analyses were performed using random-effects models, and pre-specified subgroup analyses were performed.
A total of 56 RCTs (39 drug, 17 device) were included. The pooled proportion of women enrollment was 27.0% (95%CI: 22.0% to 32.4%) in drug trials and 25.3% (95%CI: 21.0% to 29.9%) in device trials. Women were more underrepresented in HF with reduced ejection fraction (HFrEF) than in HF with preserved EF (HFpEF) trials (21.0% vs 49.6%, p < 0.001). Among drug trials reporting sex-specific effects, the pooled sex interaction for RCTs reporting HR was 0.94 (95%CI 0.89-1.01) and RR was 0.81 (95%CI 0.68-0.96), suggesting potentially greater benefit for women. No interaction was observed between HFrEF and HFpEF trials (HR: p = 0.44; RR: p = 0.95). The pooled interaction estimate on event counts was 0.90 (95%CI 0.84-0.96). For devices, the pooled sex interaction for RCTs reporting HR was 1.05 (95%CI 0.90-1.22) and RR was 0.68 (95%CI 0.50-0.93).
Women remain underrepresented in HF RCTs. Sex-stratified analyses suggest a potentially greater relative benefit of drug intervention in women, which might inform future RCTs. Further studies are required to investigate the mechanisms of these differences.

PMID:
42876202
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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