Sex-based differences in outcomes of transcatheter aortic valve replacement: a meta-analysis and meta-regression of 657,850 patients

Background Transcatheter aortic valve replacement (TAVR) is an effective treatment for symptomatic aortic stenosis (AS). Sex-based morphological and physiological differences may influence TAVR outcomes. These differences and variations in baseline characteristics may impact outcomes after TAVR between the sexes. Purpose This meta-analysis aimed to compare sex-related outcomes in over half a million patients undergoing TAVR and assess the influence of baseline characteristics via meta-regression analysis. Results The meta-analysis included 58 studies with 657,850 patients (351,927 males; 305,923 females). Females were older (81.3 vs. 80.2 years; p <0.01) with better LVEF%, while males had more comorbidities. Meta-analysis of primary outcomes showed that females had higher in-hospital mortality (RR 1.16, 95% CI 1.02–1.32; p = 0.02, I² = 76%) but lower 1-year mortality (RR 0.87, 95% CI 0.82–0.93; p < 0.01, I² = 44%). No sex differences were observed in 30-day mortality (RR 1.02, 95% CI 0.95–1.10; p = 0.52, I² = 5%) or cardiovascular mortality at 30 days (RR 1.04, 95% CI 0.92–1.18; p = 0.56, I² = 0%) and 1 year (RR 1.09, 95% CI 0.92–1.29; p = 0.31, I² = 26%). Meta-regression identified confounders (e.g., age, hypertension,heart failure with New Work Heart Association (NYHA) III/IV, prior stroke, prior atrial fibrillation, Prior percutaneous coronary intervention, prior pacemaker and valve type) explaining heterogeneity in in-hospital mortality. Females had higher risks of major bleeding (RR 1.28, 95% CI 1.16–1.41; p < 0.01, I² = 79%), vascular complications (RR 1.42, 95% CI 1.25–1.62; p < 0.01, I² = 69%), and stroke (in-hospital: RR 1.25, 95% CI 1.15–1.37; p < 0.01, I² = 40%; 30-day: RR 1.24, 95% CI 1.07–1.44; p < 0.01, I² = 0%). Conversely, acute kidney injury (AKI) was less frequent in females (RR 0.91, 95% CI 0.86–0.97; p < 0.01, I² = 54%). Conclusion Our meta-analysis, the largest and most comprehensive of its kind, reveals that females face higher short-term risks (in-hospital mortality, stroke, bleeding, vascular complications), while males have higher 1-year mortality and AKI. Despite lower 1-year mortality, females show no difference in 1-year cardiovascular mortality, suggesting their survival advantage may reflect longer life expectancy rather than TAVR effects. Peri-procedural care for females should be enhanced, and sex-specific TAVR treatment guidelines are needed.