Direct oral anticoagulants versus aspirin for prevention of overt and covert cerebral infarction: A meta-analysis

Background Studies evaluating direct oral anticoagulant (DOAC) therapy in reducing covert brain infarction (CBI), compared to aspirin monotherapy, have generally been small and yielded inconclusive results. We, therefore, performed a systematic review and meta-analysis to summarize the effect of DOAC use with CBI and ischemic stroke. Methods Using PRISMA guidelines, we systematically searched PubMed, Scopus, Embase, and the Cochrane Library from inception to August 1, 2025, for randomized controlled trials or ancillary studies of trials comparing DOACs with aspirin. Studies were included if magnetic resonance imaging (MRI) scans of the brain were performed during follow-up, and rates of CBI were reported. The primary outcome was any ischemic cerebrovascular event defined as a composite of CBI or symptomatic ischemic stroke, while the secondary outcomes were symptomatic ischemic stroke, incident CBI and incident cerebral microbleeds on follow up brain MRI. After assessing study heterogeneity, we performed a meta-analysis using random-effects inverse-variance weighted models to generate log odds ratios (ORs) and evaluate the strength of association between the type of antithrombotic therapy and outcomes. A subgroup analysis was performed stratified by the type of indication for antithrombotic therapy (primary vs. secondary prevention). Results Six studies, with a total of 3,666 patients, were eligible for inclusion in the meta-analysis. DOAC use was associated with lower odds of any ischemic cerebrovascular event (OR, 0.65; CI, 0.50-0.85; I 2 = 0.0%). In secondary analyses, DOAC use was associated with lower odds of symptomatic ischemic stroke (OR, 0.57; CI, 0.35-0.92; I 2 = 9.7%), but there was no relationship with CBI (OR, 0.81; CI, 0.61-1.07; I 2 = 0.0%), or cerebral microbleeds (OR, 1.10; CI, 0.79-1.52; I 2 = 0.0%). Conclusions In this hypothesis-generating meta-analysis of patients at risk for ischemic cerebrovascular disease, DOAC therapy, compared with aspirin, suggested a lower risk of ischemic cerebrovascular events, driven by reductions in symptomatic stroke while there was no association with covert brain infarction.