Department of Quantitative Health Sciences; Department of Medicine, Division of Cardiovascular Medicine
Cardiology | Cardiovascular Diseases | Clinical Epidemiology | Epidemiology | Health Services Research | Pharmaceutical Preparations
BACKGROUND: Direct oral anticoagulants (DOACs) have emerged as promising alternatives to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Few meta-analyses have included all DOACs that have received FDA approval for these cardiovascular indications, and their overall comparisons against VKAs have shortcomings in data and methods. We provide an updated overall assessment of the efficacy and safety of those DOACs at dosages currently approved for NVAF or VTE, in comparison with VKAs.
METHODS: We used data from Phase 3 randomized trials that compared an FDA-approved DOAC with VKA for primary prevention of stroke in patients with NVAF or for treatment of acute VTE.
RESULTS: Among trial participants with NVAF, DOAC recipients had a lower risk of stroke or systemic embolism [Pooled Odds Ratio (OR) 0.76, 95% Confidence Interval (CI) (0.68-0.84)], any stroke (0.80, 0.73-0.88), systemic embolism (0.56, 0.34-0.93), and total mortality (0.89, 0.84-0.95). Safety outcomes also showed a lower risk of fatal, major, and intracranial bleeding but higher risk for gastrointestinal bleeding (GIB). Patients with acute VTE randomized to DOACs had comparable risk of recurrent VTE and death (OR 0.88, 95% CI 0.75-1.03), recurrent DVT (0.83, 0.66-1.05), recurrent non-fatal PE (0.97, 0.75-1.25), and total mortality (0.94, 0.79-1.12). Safety outcomes for DOACs showed a lower risk of major, fatal, and intracranial bleeding, but similar risk of GIB.
CONCLUSIONS: Patients receiving DOACs for NVAF had predominantly superior efficacy and safety. Patients who were treated with DOACs for acute VTE had non-inferior efficacy, but an overall superior safety profile.
Direct oral anticoagulants, atrial fibrillation, venous thromboembolism
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Copyright: © 2018 Makam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2018 May 24;13(5):e0197583. doi: 10.1371/journal.pone.0197583. eCollection 2018. Link to article on publisher's site
Makam RC, Hoaglin DC, McManus DD, Wang V, Gore JM, Spencer FA, Pradhan R, Tran H, Yu H, Goldberg RJ. (2018). Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis. Population and Quantitative Health Sciences Publications. https://doi.org/10.1371/journal.pone.0197583. Retrieved from https://escholarship.umassmed.edu/qhs_pp/1201
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