Novel oral anticoagulants versus warfarin in non-valvular atrial fibrillation: a meta-analysis of 50,578 patients.

BACKGROUND: Warfarin, despite its known limitations, is the reference standard treatment for patients with AF and risk factors for stroke. We performed a meta-analysis of phase III trials that compare novel oral anticoagulants (NOACs) with warfarin to determine whether they improve clinical outcomes of patients with non-valvular atrial fibrillation (AF).

METHODS: Three randomized trials that compared NOACs with warfarin in AF were selected. The primary efficacy endpoint was the incidence of stroke or systemic embolism. The primary safety endpoint was the incidence of major bleeding.

RESULTS: A total of 50578 patients were included. NOACs significantly decreased stroke or systemic embolism (2.8% vs 3.5%, odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.91, P<0.001), death (6.0% vs 6.3%, OR 0.88, 95% CI 0.82-0.95, P=0.001) and stroke (2.4% vs 3.0%, OR 0.79, 95% CI 0.71-0.88, P<0.001). The reduction in stroke was mainly driven by fewer hemorrhagic strokes (0.3% vs 0.8%, OR 0.79, 95% CI 0.71-0.88, P<0.001). Major bleeding occurred in 5.0% and 5.6% of patients in the NOACs and warfarin groups (OR 0.85, 95% CI 0.69-1.05, P=0.14 in the random-effects model). NOACs were associated with lower rates of intracranial bleeding (0.6% vs 1.3%, P<0.001) and higher rates of gastrointestinal bleeding (2.3% vs 1.3%, P=0.036).

CONCLUSIONS: In patients with non-valvular AF, NOACs decrease stroke or systemic embolism, hemorrhagic stroke and mortality, with similar risk of major bleeding compared to warfarin.