Direct Oral Anticoagulants Versus Warfarin in Morbidly Obese Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis

Background: Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis recommended avoiding the use of DOACs in morbidly obese patients (body mass index >40 or weight >120 kg) because of limited clinical data. Study Question: Are DOACs effective and safe in morbidly obese patients with nonvalvular atrial fibrillation (NVAF). Data Sources: We performed a comprehensive search for published studies indexed in PubMed/ MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials that evaluated the efficacy and safety of DOACs in morbidly obese patients with NVAF. Study Design: Information on patient characteristics, comorbidities, primary anticoagulation indications, pharmacologic treatment, and outcomes were collected. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). Results: A total of 10 studies including, 89,494 morbidly obese patients with NVAF on oral anticoagulation therapy (45,427 on DOACs vs. 44,067 on warfarin) were included in the final analysis. The SSE rate was significantly lower in DOACs group compared with warfarin group [odds ratio: 0.71; 95% confidence interval (CI): 0.62-0.81; P < 0.0001; I-2 = 0%]. MB rate was also significantly lower in DOACs group compared with the warfarin group (odds ratio: 0.60; 95% CI: 0.46-0.78; P, 0.0001; I-2 = 86%). On subgroup analysis, SSE and MB event rates were significantly lower in rivaroxaban and apixaban than warfarin; however, dabigatran showed noninferiority to warfarin in SSE rate but superiority in the safety outcome. Conclusions: Our meta-analysis demonstrated that DOACs are effective and safe with statistical superiority when compared with warfarin in morbidly obese patients. Large-scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs in this cohort of patients.