Aims: Sex differences in the long-term prognosis of heart failure (HF) remain controversial, and there is a lack of comprehensive pooling of the sex differences in outcomes of HF. This study aims to characterize the sex differences in the long-term prognosis of HF and explore whether these differences vary by age, HF course, left ventricular ejection fraction, region, period of study, study design, and follow-up duration.
Methods and results: A systematic review was conducted using Medline, Embase, Web of Science, and the Cochrane Library, from 1 January 1990 to 31 March 2024. The primary outcome was all-cause mortality (ACM), and the secondary outcomes included cardiovascular mortality (CVM), hospitalization for HF (HHF), all-cause hospitalization, a composite of ACM and HHF, and a composite of CVM and HHF. Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. Ninety-four studies (comprising 96 cohorts) were included in the meta-analysis, representing 706,247 participants (56.5% were men; the mean age was 71.0 years). Female HF patients had a lower risk of ACM (HR 0.83; 95% CI 0.80, 0.85; I2 = 84.9%), CVM (HR 0.84; 95% CI 0.79, 0.89; I2 = 70.7%), HHF (HR 0.94; 95% CI 0.89, 0.98; I2 = 84.0%), and composite endpoints (ACM + HHF: HR 0.89; 95% CI 0.83, 0.95; I2 = 80.0%; CVM + HHF: HR 0.85; 95% CI 0.77, 0.93; I2 = 87.9%) compared with males. Subgroup analysis revealed that the lower risk of mortality observed in women was more pronounced among individuals with long-course HF (i.e. chronic HF, follow-up duration > 2 years) or recruited in the randomized controlled trials (P for interaction < 0.05).
Conclusion: Female HF patients had a better prognosis compared with males, with lower risks of ACM, CVM, HHF, and composite endpoints. Despite the underrepresentation of female populations in HF clinical trials, their mortality benefits tended to be lower than in real-world settings.
Registration: PROSPERO: CRD42024526100.
Keywords: Heart failure; Meta-analysis; Mortality; Prognosis; Sex differences.
Our meta-analysis showed that women were associated with lower risks of all-cause mortality, cardiovascular mortality, hospitalization for heart failure (HF), and composite endpoints but not all-cause hospitalization. The lower risk of mortality for women was more pronounced among individuals with long-course HF or recruited in the randomized controlled trials. This study highlights the significance of improving women’s socioeconomic status and addressing the undermanagement of cardiovascular disease among women worldwide.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.