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Comparative Effectiveness and Safety of Rivaroxaban in Adults With Nonvalvular Atrial Fibrillation

Aronow, Wilbert S. MD1; Shamliyan, Tatyana A. MD, MS2,*

doi: 10.1097/MJT.0000000000000890

Background: All evidence regarding benefits and harms of rivaroxaban for stroke prevention has not been appraised yet.

Study Question: What are the comparative effectiveness and safety of rivaroxaban in adults with nonvalvular atrial fibrillation?

Data Sources: Randomized controlled trials (RCTs), meta-analyses, and observational studies were identified in several databases in October 2018.

Study Design: Rapid review with evidence appraisal using the Grading of Recommendations Assessment, Development and Evaluation working group approach.

Results: Two direct RCTs (23,021 patients) suggest that rivaroxaban is noninferior to warfarin in the prevention of stroke and systemic embolism (pooled relative risk [RR] 0.73, 95% confidence interval [CI], 0.43–1.24), reduces risk of hemorrhagic stroke (RR 0.59, 95% CI, 0.38–0.92), fatal bleeding (RR 0.49, 95% CI, 0.31–0.76), and cardiac arrest (RR 0.45, 95% CI, 0.25–0.82, 2 RCTs), but increases risk of major gastrointestinal bleeding (RR 1.46, 95% CI, 1.19–1.78). In observational studies, rivaroxaban is associated with lower risk of ischemic stroke (RR 0.87, 95% CI, 0.77–0.99, 222,750 patients), acute myocardial infarction (RR 0.61, 95% CI, 0.48–0.78, 73,739 patients), and intracranial hemorrhage (RR 0.64, 95% CI, 0.45–0.92, 197,506 patients) but higher risk of gastrointestinal bleeding (RR 1.30, 95% CI, 1.19–1.42, 188,968 patients) and higher risk of mortality when compared with warfarin in European studies (RR 1.19, 103,270 patients in the UK; RR 2.02, 22,358 patients in Denmark) but lower risk of mortality in Taiwan (RR 0.58, 40,000 patients). Network meta-analyses and observational studies suggest that rivaroxaban is associated with higher risk of bleeding when compared with apixaban (RR 2.14, 72,586 patients), dabigatran (RR 1.24, 67,102 patients), and edoxaban (RR 1.32, 71,683 patients).

Conclusions: Research on the long-term comparative effectiveness, safety, and effects on quality of life between rivaroxaban and other novel oral anticoagulants is urgently needed.

1Department of Medicine and Cardiology Research, Westchester Medical Center, New York Medical College, Valhalla, NY; and

2Quality Assurance, Evidence-Based Medicine Center, Philadelphia, PA.

Address for correspondence: Senior Director, Quality Assurance, Evidence-Based Medicine Center, Elsevier, 1600 JFK Blvd, Philadelphia, PA 19103. E-mail:

Supported by Elsevier Evidence-based Medicine Center.

The authors have no conflicts of interest to declare.

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