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Meta-Analysis
. 2018 May 24;13(5):e0197583.
doi: 10.1371/journal.pone.0197583. eCollection 2018.

Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis

Raghavendra Charan P Makam  1   2   3 , David C Hoaglin  1 , David D McManus  2 , Victoria Wang  1 , Joel M Gore  2 , Frederick A Spencer  4 , Richeek Pradhan  1 , Hoang Tran  1 , Hong Yu  1   2   5   6   7 , Robert J Goldberg  1
Affiliations
Meta-Analysis

Efficacy and safety of direct oral anticoagulants approved for cardiovascular indications: Systematic review and meta-analysis

Raghavendra Charan P Makam et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study flow diagram.
Fig 2
Fig 2. Forest plot of pooled odds ratios (with 95% CI) of various efficacy outcomes for FDA-approved direct oral anticoagulants versus warfarin for thromboembolic stroke prophylaxis in non-valvular atrial fibrillation.
Fig 3
Fig 3. Forest plot of pooled odds ratios (with 95% CI) of various adverse drug events for FDA-approved direct oral anticoagulants versus warfarin for thromboembolic stroke prophylaxis in non-valvular atrial fibrillation.
Fig 4
Fig 4. Forest plot of pooled odds ratios (with 95% CI) of various efficacy outcomes for FDA-approved direct oral anticoagulants versus warfarin for treatment of VTE.
Fig 5
Fig 5. Forest plot of pooled odds ratios (with 95% CI) of various adverse drug events for FDA-approved direct oral anticoagulants versus warfarin for treatment of VTE.
See this image and copyright information in PMC

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