Key result
Male sex linked to ~95% higher all-cause mortality in patients with HFrEF.
Why the study?
Sex-related differences in prognosis among patients with HFrEF have been described, but their association with long-term all-cause and cardiovascular mortality remains incompletely characterised, particularly when accounting for non-cardiovascular death as a competing event.
Observational (n=1,510)
No
In a real-world HFrEF cohort, male sex is independently associated with higher long-term all-cause and cardiovascular mortality compared to female sex, even after accounting for competing non-cardiovascular death.
Male sex associated with higher HFrEF mortality warrants no practice change; extends prior observations but leaves open causal validation and targeted interventions.
Background/Objectives: Sex-related differences in prognosis among patients with heart failure with reduced ejection fraction (HFrEF) have been described, but their association with long-term all-cause and cardiovascular mortality remains incompletely characterised. This study investigated these associations in a real-world HFrEF cohort, accounting for non-cardiovascular death as a competing event. Methods: We conducted a single-centre, retrospective, longitudinal observational study of 1510 consecutive patients with HFrEF followed between 2011 and 2023; 1158 (76.7%) were men and 352 (23.3%) were women. All-cause mortality was assessed using Kaplan–Meier methods and Cox regression. Multivariable models used a complete-case approach. Cardiovascular mortality was analysed using cause-specific Cox regression and the Fine–Gray model, with non-cardiovascular death and death of unknown cause treated as competing events. Interaction terms between sex and year of inclusion were used to assess potential changes in the association across the study period. Results: No statistically significant between-sex difference in cumulative all-cause mortality was detected at one year (3.7% in men vs. 3.8% in women; p = 0.95). Exploratory pointwise comparisons showed higher cumulative mortality in men at five years (24.8% vs. 16.0%; p = 0.002) and ten years (49.3% vs. 39.8%; p = 0.046). After multivariable adjustment, male sex was associated with higher all-cause mortality (HR, 1.95; 95% CI, 1.47–2.59; p < 0.001). Male sex was also associated with cardiovascular mortality in the cause-specific analysis (HR, 2.46; 95% CI, 1.54–3.92; p < 0.001) and after accounting for non-cardiovascular death as a competing event (subdistribution HR, 2.12; 95% CI, 1.32–3.39; p = 0.002). No significant interaction was observed between sex and year of inclusion. Conclusions: In this real-world HFrEF cohort, male sex remained associated with higher all-cause and cardiovascular mortality after adjustment for measured baseline covariates. The association with cardiovascular mortality persisted in competing-risk analysis. These observational findings do not establish a causal or time-varying effect of sex.
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López‐López et al. (2026) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=1,510). Male sex vs. Female sex was evaluated on All-cause mortality (HR 1.95, 95% CI 1.47-2.59, p=<0.001). Male sex was associated with higher adjusted all-cause (HR 1.95; 95% CI 1.47-2.59; p<0.001) and cardiovascular mortality (sHR 2.12; 95% CI 1.32-3.39) in patients with HFrEF.
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