May 24, 2018PLoS ONEOpen Access

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

View Full Paper

Ask AI

Bookmark

Why the study?

Do FDA-approved DOACs improve efficacy and safety compared to vitamin K antagonists in patients with non-valvular atrial fibrillation or acute venous thromboembolism?

Structured PICO

Do FDA-approved DOACs improve efficacy and safety compared to vitamin K antagonists in patients with non-valvular atrial fibrillation or acute venous thromboembolism?

Population

80,311 participants from 9 Phase 3 randomized trials, including 58,271 patients with non-valvular atrial fibrillation (NVAF) (average age 71.6 years, 37.4% women) and 22,040 patients with acute venous thromboembolism (VTE) (average age 56.2 years, 41.6% women).

Intervention

Direct oral anticoagulants (DOACs) as a class (dabigatran, apixaban, rivaroxaban, or edoxaban) at FDA-approved standard dosages.

Comparator

Vitamin K antagonists (warfarin dose-adjusted to achieve an international normalized ratio between 2.0 and 3.0) or enoxaparin followed by VKA.

Outcome

Occurrence of stroke and systemic embolism (primary efficacy outcome for NVAF) and recurrent VTE and related death (primary efficacy outcome for VTE).composite

DOACs demonstrate superior efficacy and safety in NVAF and non-inferior efficacy with superior safety in VTE compared to vitamin K antagonists.

Limitations

Modest number of trials
Differences in time in therapeutic range for warfarin across trials (e.g., ROCKET AF)
Differences in baseline CHADS2 scores across trials
Exclusion of EINSTEIN-PE trial due to population differences

Implication

Supports first-line DOAC use over VKAs in NVAF and VTE; confirms and extends RCT meta-evidence for guidelines.

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.