Effects of direct oral anticoagulants on cardiac outcomes in atrial fibrillation: a systematic review and network meta-analysis

Background Direct oral anticoagulants (DOACs) reduce thromboembolism in atrial fibrillation (AF), but their effect on cardiac outcomes is less studied. Methods Systematic review and network meta-analysis were performed on AF patients on DOACs/vitamin K antagonists (VKAs). Both observational studies and randomized clinical trials (RCTs) were included. Endpoints were myocardial infarction (MI) and major adverse cardiac events (MACE). Rankograms and SUCRA were performed. Sub-group analysis included age (</≥ 75 years) and length of follow-up (</≥ 12 months). Results 50 studies (3 RCTs, 4 post hoc analyses of RCTs and 43 observational studies) with 1,769,987 patients were included (59.9% on DOACs and 45.3% women). The MI risk (46 studies with 1,554,704 patients) was lower in all DOACs compared to VKA (apixaban: hazard ratio [HR] 0.83, 95% credible interval [95%CI 0.72–0.96], edoxaban: HR 0.68, 95%CI 0.53–0.86, rivaroxaban: HR 0.84, 95%CI 0.74–0.95, dabigatran: HR 0.85, 95%CI 0.75–0.97). SUCRA showed edoxaban as first choice for preventing MI overall. In patients aged < 75 years, a lower MI risk was found for edoxaban (HR 0.60, 95%CI 0.41–0.85), while in those aged ≥ 75 years, no significant difference was found among anticoagulants. Heterogeneity was low in all analyses. Network meta-analysis showed no differences among DOACs. Compared to VKA, apixaban (HR 0.77, 95%CI 0.63–0.97) was associated with lower MACE risk. Analysis of SUCRA showed apixaban as first choice for preventing MACE overall and in patients treated for < 12 months. Conclusion DOACs were associated with a lower risk of MACE/MI in AF. The effect of DOACs on cardiovascular risk differs according to aging and follow-up length. However, our findings are based on indirect evidence, and further studies are needed. PROSPERO registration number CRD42023407778.