• Angela Lowenstern, Sana M Al-Khatib, Lauren Sharan, Ranee Chatterjee, Nancy M Allen LaPointe, Bimal Shah, Ethan D Borre, Giselle Raitz, Adam Goode, Roshini Yapa, J Kelly Davis, Kathryn Lallinger, Robyn Schmidt, Andrzej S Kosinski, and Gillian D Sanders.
• Duke University School of Medicine, Durham, North Carolina (A.L., S.M.A., L.S., R.C., E.D.B., G.R., A.G., K.L., R.S., A.S.K.).
• Ann. Intern. Med. 2018 Dec 4; 169 (11): 774-787.

BackgroundThe comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remain uncertain.PurposeTo compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with nonvalvular AF.Data SourcesEnglish-language studies in several databases from 1 January 2000 to 14 February 2018.Study SelectionTwo reviewers independently screened citations to identify comparative studies of treatments to prevent stroke in adults with nonvalvular AF who reported thromboembolic or bleeding complications.Data ExtractionTwo reviewers independently abstracted data, assessed study quality and applicability, and rated strength of evidence.Data SynthesisData from 220 articles were included. Dabigatran and apixaban were superior and rivaroxaban and edoxaban were similar to warfarin in preventing stroke or systemic embolism. Apixaban and edoxaban were superior and rivaroxaban and dabigatran were similar to warfarin in reducing the risk for major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction P > 0.05), and patients younger than 75 years had lower bleeding rates with dabigatran (interaction P < 0.001). The benefit of treatment with apixaban was consistent in many subgroups, including those with renal impairment, diabetes, and prior stroke (interaction P > 0.05 for all). The greatest bleeding risk reduction was observed in patients with a glomerular filtration rate less than 50 mL/min/1.73 m2 (P = 0.003). Similar treatment effects were observed for rivaroxaban and edoxaban in patients with prior stroke, diabetes, or heart failure (interaction P > 0.05 for all).LimitationHeterogeneous study populations, interventions, and outcomes.ConclusionThe available direct-acting oral anticoagulants (DOACs) are at least as effective and safe as warfarin for patients with nonvalvular AF. The DOACs had similar benefits across several patient subgroups and seemed safe and efficacious for a wide range of patients with nonvalvular AF.Primary Funding SourcePatient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069999).

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