Sex-based disparities in cardiovascular outcomes: real-world evidence following chimeric antigen receptor T-cell therapy

Background Cardiovascular complications are increasingly recognized following chimeric antigen receptor T-cell (CAR-T) therapy, yet potential sex-based differences in cardiovascular risk remain incompletely defined. We evaluated sex-based differences in major adverse cardiovascular events (MACE) and cardiovascular complications following CAR-T therapy. Methods Using the TriNetX Global Research Network, we identified adults treated with CAR-T therapy between 2015 and 2025. Male and female patients were propensity score–matched 1:1 on baseline characteristics. The primary outcome was MACE, defined as myocardial infarction, stroke, or all-cause mortality, assessed at 1- and 2-year follow-up. Secondary outcomes included all-cause mortality and other cardiovascular complications. Outcomes were compared using risk ratios and Cox proportional hazards models. Results Among 4,944 matched patients (2,472 males and 2,472 females), baseline characteristics were well balanced. At 1 year, males had a higher incidence of MACE compared with females (558 vs. 437 events; RR: 1.22, 95% CI: 1.09–1.36), with a higher hazard on time-to-event analysis (HR: 1.22, 95% CI: 1.08–1.38). This association persisted at 2 years (697 vs. 593 events; RR: 1.15, 95% CI: 1.05–1.26; HR: 1.18, 95% CI: 1.06–1.32). At 2 years, males also had a higher risk of all-cause mortality and higher risks of atrial fibrillation, ventricular arrhythmias, high-grade atrioventricular block, and pericarditis. Conclusions Male sex was associated with a higher risk of MACE following CAR-T therapy, along with a greater burden of arrhythmic and conduction abnormalities. These findings highlight the importance of incorporating biological sex into cardiovascular risk assessment and monitoring strategies in patients undergoing CAR-T therapy.