Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis of Observational Studies

摘要

Background There are no head-to-head randomized controlled trials comparing different direct oral anticoagulants (DOACs). Thus, we systematically reviewed and meta-analyzed observational studies assessing the comparative effectiveness and safety of DOACs for stroke prevention in patients with atrial fibrillation (AF). Methods We systematically searched MEDLINE and EMBASE up to February 2019 for observational studies comparing different DOACs head-to-head in patients with AF. Two independent reviewers identified studies, extracted data, and assessed the risk of bias using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Random-effects models were used to meta-analyze data across higher-quality studies. Results We identified 25 cohort studies including 1,079,565 patients with AF treated with DOACs. Meta-analysis of the 19 studies at moderate risk of bias yielded a similar risk of ischemic stroke for rivaroxaban versus dabigatran (six studies; hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.83-1.04; I-2: 0%), apixaban versus dabigatran (five studies; HR 0.94; 95% CI 0.82-1.09; I-2: 0%), and apixaban versus rivaroxaban (four studies; HR 1.07; 95% CI 0.93-1.23; I-2: 0%). Regarding major bleeding, there was an increased risk for rivaroxaban versus dabigatran (six studies; HR 1.33; 95% CI 1.20-1.47; I-2: 22%) and decreased risks for apixaban versus either dabigatran (eight studies; HR 0.71; 95% CI 0.64-0.78; I-2: 0%) or rivaroxaban (eight studies; HR 0.56; 95% CI 0.48-0.65; I-2: 69%). Conclusions As head-to-head trials comparing different DOACs do not exist, available evidence derives exclusively from observational studies. These data suggest that while dabigatran, rivaroxaban, and apixaban have a similar effect on the risk of ischemic stroke, apixaban may be associated with a decreased risk of major bleeding compared with either dabigatran or rivaroxaban.