Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation Across BMI Categories: A Systematic Review and Meta-Analysis

Objectives Concerns have arisen recently over the relationship between body mass index (BMI) and outcomes in atrial fibrillation (AF) patients with direct oral anticoagulants (DOACs). This meta-analysis aimed to explore if there is an obesity paradox in anticoagulated AF patients, and compare the treatment effects between DOACs and warfarin in AF patients across BMI categories. Methods We systematically searched the PubMed and Embase databases until February 26, 2019 for relevant studies. Risk ratios (RRs) with 95% confidence intervals (CIs) were extracted and pooled by a random-effects model. Results A total of nine studies were included. Compared with normal weight, underweight was associated with an increased risk of stroke or systemic embolism (SSE) (RR 1.98, 95% CI 1.19-3.28), whereas either overweight or obesity was related with reduced rates of SSE (overweight: RR 0.81, 95% CI 0.71-0.91; obesity: RR 0.69, 95% CI 0.61-0.78) and all-cause death (overweight: RR 0.73, 95% CI 0.64-0.83; obesity: RR 0.72, 95% CI 0.66-0.79). Compared with patients receiving warfarin, patients receiving DOACs who were underweight, normal weight or overweight all had decreased risks of SSE (underweight: RR 0.61, 95% CI 0.46-0.80; normal weight: RR 0.72, 95% CI 0.58-0.91; overweight: RR 0.87, 95% CI 0.76-0.99) and major bleeding (underweight: RR 0.67, 95% CI 0.55-0.81; normal weight: RR 0.72, 95% CI 0.58-0.90; overweight: RR 0.83, 95% CI 0.71-0.96), while obese DOAC users were at no higher risks for SSE and major bleeding. Conclusions There may be an obesity paradox in anticoagulated patients with AF. DOACs have better efficacy and safety profiles than warfarin in underweight, normal weight and overweight patients, and are not inferior to warfarin in obese patients.