Background: Stroke remains a primary cause of global death and disability, imposing a substantial socioeconomic burden. Aspirin is a widely utilized and inexpensive agent for cardiovascular prevention, but its net clinical benefit in high-risk vascular patients is increasingly debated due to the critical trade-off between reducing ischemic events and elevating the risk of major bleeding. As therapeutic management of vascular risk factors improves, a contemporary synthesis of evidence is essential to refine clinical practice.

Objective: To conduct a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) to rigorously quantify the efficacy (ischemic stroke reduction) and safety (major bleeding events) of aspirin for stroke prevention in patient populations defined as having high vascular risk.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials through May 2025. We included RCTs that compared daily aspirin against placebo or no treatment in adults identified with high vascular risk. The primary efficacy outcome was ischemic stroke, and the primary safety outcome was major bleeding. Data were pooled using a random-effects model to calculate summary Risk Ratios (RR) with 95% Confidence Intervals (CIs), and heterogeneity was assessed using the I² statistic.

Results: Our search identified 15 eligible RCTs, comprising a total of 152,477 participants. The meta-analysis revealed that aspirin therapy was associated with a statistically significant 14% relative reduction in the risk of ischemic stroke compared with control (RR 0.86, 95% CI 0.78-0.95; P=0.003; I²=15%). Conversely, aspirin use led to a statistically significant and clinically important 45% relative increase in the risk of major bleeding (RR 1.45, 95% CI 1.25-1.68; P<0.001; I²=22%). This included a 38% heightened risk of intracranial hemorrhage (RR 1.38, 95% CI 1.15-1.65). While aspirin also reduced non-fatal myocardial infarction, it had no significant effect on all-cause mortality.

Conclusion: In patients with high vascular risk, aspirin confers a modest reduction in the incidence of ischemic stroke but at the cost of a substantial increase in the risk of major bleeding. This trade-off results in no net mortality benefit. The decision to prescribe aspirin, especially for primary prevention, must therefore move beyond generalized risk categories and requires a meticulous, individualized assessment of a patient's absolute ischemic and bleeding risks, facilitated by a shared decision-making process.

Aspirin, Stroke Prevention, Meta-Analysis, Systematic Review

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