Optimal duration of dual antiplatelet therapy for secondary stroke prevention: A systematic review and meta-analysis

Dual antiplatelet therapy (DAPT) is recommended for secondary prevention after minor ischemic stroke or high-risk transient ischemic attack (TIA). Although short-term DAPT is widely used, uncertainty remains regarding how the balance between ischemic benefit and bleeding risk evolves. We aimed to characterize the temporal profile of DAPT efficacy and safety using week-by-week outcome assessments.

We conducted a systematic review and meta-analysis in accordance with Cochrane and PRISMA guidelines. Secondary analyses of randomized clinical trials reporting weekly stratified outcomes of DAPT versus aspirin monotherapy were included from database inception through October 2025. The primary efficacy outcome was major ischemic events (MIE), and the primary safety outcome was major bleeding. Outcomes were analyzed on a weekly basis using a random-effects model.

Four RCTs comprising 27,167 patients met the inclusion criteria. DAPT significantly reduced MIE risk in the first week (4.098% vs 5.759%; RR = 0.71; 95% CI: 0.64-0.79) but not in weeks 2-4. By week 5, aspirin monotherapy was associated with lower MIE risk (0.285% vs. 0.074%; RR = 3.64; 95% CI: 1.45-9.14). DAPT increased major bleeding in weeks 1 (0.221% vs. 0.066%; RR = 2.48; 95% CI: 1.11-5.50) and 2 (0.139% vs 0.036%; RR = 3.27; 95% CI: 1.31-8.19). The benefit-to-risk ratio was most favorable in week 1 (12.87), decreasing sharply in weeks 2-3 (1.68). A time-course analysis confirmed the greatest ischemic risk reduction in week 1, with diminishing efficacy thereafter, while bleeding risk remained elevated for two weeks.

This time-course meta-analysis suggests that the ischemic benefit of DAPT after minor ischemic stroke or high-risk TIA is concentrated early after treatment initiation, with attenuation over subsequent weeks, while bleeding risk persists during the early treatment period. These findings support the exploration of shorter, individualized DAPT strategies in patients at higher bleeding risk, while warranting cautious interpretation given heterogeneity across studies and the reliance on secondary analyses of randomized trials.