SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: A Retrospective Cohort Analysis of Sex-Specific Cardiovascular Outcomes.

Introduction: Sex-based differences in outcomes among patients with heart failure with reduced ejection fraction (HFrEF) treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. This study aimed to evaluate sex-specific differences in cardiovascular outcomes in patients with HFrEF receiving SGLT2 inhibitors alongside guidelinedirected medical therapy (GDMT).

Methods: We conducted a retrospective cohort study using the TriNetX global research network. Adults with HFrEF treated with SGLT2is and GDMT were stratified by sex. Propensity score matching (PSM) was used to balance baseline demographics, comorbidities, medications, and laboratory data. Primary outcomes were all-cause mortality and acute heart failure (HF) events; secondary outcomes included hospitalizations, arrhythmias, renal outcomes, and advanced therapies.

Results: After PSM, 17,408 male and 17,408 female patients were analyzed. Male patients had lower odds of acute HF events (aOR: 0.949; 95% CI: 0.909-0.991), all-cause hospitalizations (aOR: 0.933; 95% CI: 0.895-0.973), and renal failure (aOR: 0.915; 95% CI: 0.870-0.962). No significant differences were observed in all-cause mortality (aOR: 1.003; 95% CI: 0.926-1.087) or heart transplantation, although LVAD use was more frequent in males (aOR: 1.416; 95% CI: 1.053-1.905).

Discussion: The findings highlighted potential sex-based disparities in outcomes for patients with HFrEF on SGLT2is. Differential prescribing patterns, comorbidity burden, or timing of therapy initiation may contribute to observed differences.

Conclusion: Among HFrEF patients treated with SGLT2is, males experienced lower risks of HF events, hospitalizations, and renal failure compared to females, despite similar mortality. Further research is needed to understand and address sex-specific disparities in HFrEF management.