We included 3 RCTs comparing DOAC to Aspirin in patients with embolic stroke of undetermined source (ESUS). The pooled results showed that death from any cause (OR = 1.09; 95% CI [0.84, 1.41]; I² = 0%; p = 0.522), cardiovascular death (OR = 1.10; 95% CI [0.62, 1.94]; I² = 15%; p = 0.749), hemorrhagic stroke (OR = 2.21; 95% CI [0.30, 16.07]; I² = 78%; p = 0.433), intracranial hemorrhage (OR = 1.87; 95% CI [0.48, 7.26]; I² = 84%; p = 0.364), disabling stroke (OR = 0.92; 95% CI [0.39, 2.16]; I² = 84%; p = 0.845), ischemic stroke (OR = 0.91; 95% CI [0.77, 1.09]; I² = 0%; p = 0.307), recurrent stroke (OR = 0.95; 95% CI [0.75, 1.22]; I² = 62%; p = 0.710), major bleeding (OR = 1.71; 95% CI [0.84, 3.50]; I² = 73%; p = 0.140), myocardial infarction (OR = 0.92; 95% CI [0.55, 1.55]; I² = 16%; p = 0.756) and systemic embolism (OR = 0.52; 95% CI [0.21, 1.25]; I² = 0%; p = 0.144) were not statistically different between the DOAC and Aspirin groups.

In patients with ESUS, DOAC therapy did not show any significant difference with Aspirin for death from any cause, cardiovascular death, hemorrhagic stroke, intracranial hemorrhage, disabling stroke, ischemic stroke, recurrent stroke, major bleeding, MI and systemic embolism.