Background:

Atrial fibrillation (AF) and venous thromboembolism (VTE) are common conditions requiring anticoagulation in patients with severe obesity (body mass index ≥40 kg/m²). Comparative safety and efficacy data for direct oral anticoagulants (DOACs) vs warfarin in this population remain limited.

Objective:

To compare the safety and efficacy of DOACs and warfarin in non-valvular atrial fibrillation (NVAF) and VTE in patients with severe obesity in a real-world setting.

Methods:

This single-center, retrospective matched cohort study included adults with severe obesity receiving a DOAC or warfarin for NVAF or VTE from January 1, 2019, to December 31, 2024. Patients were matched by age, sex, and indication. Primary outcomes were composite thrombotic events (recurrent VTE or ischemic stroke occurrence) and composite bleeding events (clinically relevant non-major and major bleed). Secondary outcomes were assessments of predictors for these events.

Results:

The study included 182 patients, 91 per cohort. Composite bleeding was significantly higher in the warfarin group (39.6% vs 23.1%, P = 0.017), but it was not significantly different after adjustment for time on therapy. Composite thrombotic events were similar between groups (12.1% vs 9.9%, P = 0.89). History of major bleed (hazard ratio [HR] = 2.37, P = 0.022, 95% confidence interval [CI] = [1.13-4.96]) and concomitant antiplatelet use (HR = 3.80, P < 0.001, 95% CI = [1.98-7.26]) were predictors for bleeding. History of cerebrovascular accident (CVA)/transient ischemic attack (TIA) (HR = 3.34, P = 0.014, 95% CI = [1.28-8.74]) was a predictor for thrombosis.

Conclusion:

DOACs demonstrated comparable safety and efficacy to warfarin in patients with severe obesity with NVAF or VTE.