Concomitant antiplatelet therapy in anticoagulated TAVI patients with atrial fibrillation: impact of sex on bleeding and ischaemic events in ENVISAGE-TAVI AF

Background In patients with atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI), oral anticoagulation is indicated, yet concomitant antiplatelet therapy (APT) is frequently prescribed for concurrent ischaemic prevention indications. It remains unknown whether the risk-benefit profile of concomitant APT differs by sex in this patient population. Purpose To determine if the risk-benefit profile of oral anticoagulation with concomitant APT differs by sex in patients with AF undergoing TAVI. Methods This post hoc analysis used the ENVISAGE-TAVI AF safety analysis set (N = 1377), in which patients received edoxaban or vitamin K antagonist therapy after successful TAVI. In this analysis, patients were stratified by sex and by any APT exposure during the full study period. Primary outcomes included net adverse clinical events (NACE), a composite of death from any cause, myocardial infarction, ischaemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. Secondary outcomes included individual components of the primary outcome. Results Among 1377 anticoagulated patients, 719 were men (52.2%) and 658 were women (47.8%). Concomitant APT was used in 436 (60.6%) men and 388 (59.0%) women. Among patients receiving concomitant APT, both female and male patients had a higher prevalence of prior myocardial infarction and percutaneous coronary intervention, although these characteristics were observed more frequently in male patients than female patients (Table). Male patients with vs without APT were also more likely to have a higher prevalence of history of stroke/transient ischaemic attack, peripheral arterial disease, hypercholesterolaemia, and diabetes (Table). One hundred ninety-seven (50.8%) female patients and 214 (49.1%) male patients on APT were randomised to edoxaban. Risk of NACE was higher with APT in both males and females (Figure). The risk increase of major bleeding with APT was attenuated in males (hazard ratio [HR], 1.34; 95% confidence interval [CI], [0.84–2.15]) compared with females (HR 2.22 [1.36–3.63], P = 0.1 for interaction). Similarly, APT was associated with a higher risk of major gastrointestinal (GI) bleeding in females (HR, 3.61; 95% CI, 1.60–8.12) but not in males (HR, 1.11; 95% CI, 0.59–2.10; P = 0.03 for interaction). No statistically significant differences were noted for secondary outcomes (Figure). Conclusions Among anticoagulated TAVI patients with AF, concomitant APT was associated with a higher risk of NACE. Bleeding risk, particularly major GI bleeding, was higher in females compared with males. APT should be avoided in the absence of a strong indication in anticoagulated patients with AF after TAVI; sex-specific bleeding vulnerability may warrant greater caution.