Direct oral anticoagulants for stroke prevention in patients with atrial fibrillation: meta-analysis by geographic region with a focus on European patients

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To analyse clinical outcomes with direct oral anticoagulants in patients with atrial fibrillation according to geographic region.


We systematically searched MEDLINE, CENTRAL, websites of regulatory agencies, clinical trials registers and conference proceedings for randomized controlled trials of direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban or edoxaban) against warfarin for prophylaxis of stroke and systemic embolic events (SEE) in patients with atrial fibrillation (AF). Two investigators independently extracted data. Relative risks of stroke and SEE as well as major bleeding depending on geographic region were estimated using a random effect meta-analysis.


Five trials in 72 963 patients were analysed; 32 089 (44%) patients were recruited in Europe (Western Europe: 13 676; Eastern Europe: 18 413). We found significant subgroup differences for stroke/SEE depending on the geographic region (interaction P = 0.003; I2 88.5%), with a neutral effect of the DOAC vs. warfarin in Europe [relative risk (RR) 0.97, 95% confidence interval (CI) 0.85–1.11, I2 0%] and a significant reduction of stroke/SEE in other regions including North America, Latin America and Asia-Pacific/other (RR 0.72, 95% CI 0.63–0.83, I2 33%). There was a similar reduction in risk of major bleeding in Europe (RR 0.82, 95% CI 0.73–0.92, I2 0%) and in other regions (RR 0.86, 95% CI 0.72–1.02, I2 78%).


The DOAC did not provide additional benefit in reducing the risk of stroke/SEE compared with warfarin in European patients with AF, but were generally associated with a lower bleeding tendency than warfarin regardless of geographic region.

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