January 12, 2026Frontiers in Neurology2 citationsOpen Access

Dual antiplatelet therapy use after non-cardioembolic ischemic stroke or transient ischemic attack: a meta-analysis of trials and cohort studies

AHAdmire HlupeniSt. Luke's Hospital YAYusra AroojSt. Luke's Hospital AAAdebisi AdejolaSt. Luke's Hospital

Structured PICO

Does dual antiplatelet therapy reduce recurrent stroke compared to single antiplatelet therapy in adults with non-cardioembolic transient ischemic attack or ischemic stroke?

Population

123,136 adults (≥18 years) with non-cardioembolic transient ischemic attack (TIA) or ischemic stroke (nc-IS) of NIHSS ≤15 across 27 studies (18 randomized trials and 9 observational cohorts).

Intervention

Dual antiplatelet therapy (DAPT), defined as the concurrent use of two antiplatelet agents (e.g., aspirin-clopidogrel, aspirin-ticagrelor, aspirin-dipyridamole, aspirin-cilostazol, cilostazol-clopidogrel; excluding ticlopidine).

Comparator

Single antiplatelet therapy (SAPT).

Outcome

Recurrent stroke (either as a standalone endpoint or as part of a composite vascular outcome) and major bleeding.hard clinical

Early, time-limited dual antiplatelet therapy with a loading dose significantly reduces recurrent stroke risk after non-cardioembolic TIA or mild-to-moderate ischemic stroke, with a modest increase in major bleeding.

Abstract

Background Recurrent stroke burden exceeds 10% within the first year. Dual antiplatelet therapy (DAPT) is recommended for short-term secondary prevention after non-cardioembolic high-risk TIA or ischemic stroke (nc-IS), yet uncertainty persists regarding its true efficacy, optimal timing, duration, regimen, and bleeding risk. Aims To evaluate the efficacy and safety of DAPT vs. single antiplatelet therapy (SAPT) after TIA or nc-IS and to identify clinical and study-level effect modifiers. Methods PubMed, Embase, and Scopus were searched through October 13, 2025, for randomized trials (RTs) and cohort studies comparing DAPT and SAPT in adults (≥18 years) with TIA or nc-IS. The review was registered in PROSPERO (CRD420251017979). Recurrent stroke and major bleeding were the primary efficacy and safety outcomes of interest, respectively. Eligible studies included those comparing any DAPT vs. SAPT regimen reporting recurrent ischemic stroke or major bleeding. Two reviewers independently screened studies using predefined criteria and resolved discrepancies by consensus. Data were extracted independently by two reviewers following PRISMA guidelines. Study quality was assessed using the Cochrane RoB 2 and Newcastle–Ottawa tools. Pooled risk ratios (pRRs; 95% CIs) were calculated using random-effects models. Subgroup and meta-regression analyses explored treatment modifiers, and certainty of evidence was graded using GRADE. Data were analyzed using Stata version 18.5. Results Twenty-seven studies (18 RTs and 9 observational; 123,136 participants) were included. DAPT was associated with significant reduction in stroke recurrence compared with SAPT (pRR 0.83; 95% CI 0.78–0.88; I 2 = 57%). Benefit was greatest when DAPT was initiated ≤24 h-7 days and continued short-term (≤90 days), particularly when initiated with a loading dose. Efficacy was consistent across age, sex, stroke severity (including NIHSS 3–≤15), study design, and geographic setting, and extended to other DAPT regimens beyond aspirin-clopidogrel combinations. Major bleeding occurred more often with DAPT (pRR 1.29; 95% CI 1.00–1.66; I 2 = 60%). Bleeding risk appeared slightly higher with aspirin-clopidogrel regimens and among women but was otherwise consistent across subgroups. Conclusion Early, time-limited DAPT with a loading dose was associated with lower stroke recurrence and modest bleeding risk, with benefits extending to mild-to-moderate strokes and alternative combinations beyond the standard aspirin–clopidogrel. Systematic review registration https://www.crd.york.ac.uk/PROSPERO , identifier CRD420251017979.

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