Dual Antithrombotic Therapy Versus Anticoagulation Alone After Ischemic Stroke in Patients With Atrial Fibrillation and Atherosclerotic Disease: A Meta-Analysis of Efficacy and Safety Outcomes

Patients with atrial fibrillation and concomitant atherosclerotic disease remain at risk of recurrent ischemic events despite anticoagulation. The benefit of adding antiplatelet therapy to direct oral anticoagulants (DOACs) is still uncertain due to the potential for increased bleeding risk. A systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews. Both randomized and observational studies comparing DOAC plus antiplatelet therapy with DOAC monotherapy were included. The primary outcomes assessed were recurrent ischemic stroke and major bleeding. Eight studies were included in total, comprising 7 cohort studies and 1 randomized controlled trial. The analysis showed no significant difference in recurrent ischemic stroke between combination therapy and DOAC monotherapy (risk ratio, 0.96, 95% confidence interval, 0.80-1.14). Similarly, there were no significant differences observed in all-cause mortality, cardiovascular mortality, myocardial infarction, composite outcomes, or intracranial bleeding. However, major bleeding was significantly higher in the group receiving combination therapy (risk ratio, 1.43, 95% confidence interval, 1.06-1.93). Overall, the addition of antiplatelet therapy to DOACs did not provide any significant improvement in efficacy outcomes but was associated with an increased risk of major bleeding. These findings suggest that treatment should be individualized and highlight the need for further large-scale randomized controlled trials to better define the role of combination therapy in this patient population.