Effectiveness of direct oral anticoagulants for all‐cause mortality and cardiovascular events in overweight and obese patients with atrial fibrillation: Insight from the nationwide START registry

Background: Overweight and obesity are highly prevalent in atrial fibrillation (AF) patients, yet the best anticoagulant strategy for this group is still unclear. We evaluated the risk of all-cause mortality and cardiovascular events (CVEs) in overweight and obese AF patients treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). Methods: We analysed 10,259 AF patients on anticoagulants from the prospective nationwide START registry. Overweight was defined as BMI 25-29.9 kg/m2 and obesity as BMI ≥30 kg/m2. Mortality risk was assessed with Cox proportional hazards models, and CVEs with Fine-Grey models accounting for competing risks. Additional modelling strategies, subgroup analyses, and propensity score matching were performed to explore data and ensure robustness. Results: Overall, 6534 (63.7%) patients had BMI >25 kg/m2 (65.7% overweight, 34.3% obese). Over a median follow-up of 17.4 months, 408 deaths and 481 CVEs occurred. DOACs' use was associated with a lower risk of all-cause mortality (HR 0.57, 95% CI 0.46-0.70, p < 0.001) and CVEs (sHR 0.71, 95% CI 0.59-0.86, p < 0.001) versus VKAs. The inverse association of DOACs with mortality was evident in both overweight (HR 0.52, 95% CI 0.39-0.68, p < 0.001) and obese patients (HR 0.69, 95% CI 0.48-0.98, p = 0.040), while the reduction in CVEs reached significance only in the overweight group. Conclusions: In this nationwide registry, DOACs were associated with lower risks of mortality and CVEs compared with VKAs across BMI groups, though the CVE effect was not evident in obese patients. These findings suggest a potential mortality advantage of DOACs irrespective of BMI, warranting further confirmation.