Loading-dose dual antiplatelet therapy for early motor deterioration in minor stroke: a randomized controlled trial

OBJECTIVE: To determine whether loading-dose dual antiplatelet therapy (DAPT) reduces early motor deterioration in supratentorial non-cardioembolic ischemic stroke with motor deficits. METHOD: This single-center, parallel-group randomized controlled trial was conducted in Japan from 1 July 2023, to 30 June 2025. Patients aged 20-85 years presenting within 48 hours of onset with supratentorial non-cardioembolic ischemic stroke, unilateral motor deficit, and no ≥ 50% stenosis or proximal large artery occlusion were randomized 1:1 to loading-dose DAPT or non-loading antiplatelet therapy. The primary outcome was motor deterioration within 7 days, defined as an increase of ≥1 point in the affected-side National Institutes of Health Stroke Scale limb motor subscore. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using modified Poisson regression. RESULTS: Of 189 randomized patients, 188 were included in the primary analysis. Motor deterioration occurred in 15/98 patients (15%) in the loading-dose DAPT group and 32/90 (36%) in the non-loading group (RR 0.43; 95% CI, 0.25-0.74). Favorable functional outcomes were more frequent with loading-dose DAPT at day 21 (76% vs 61%; RR 1.24; 95% CI, 1.01-1.51) and day 90 (90% vs 73%; RR 1.23; 95% CI, 1.06-1.42). One intracerebral hemorrhage requiring surgery and one fatal pulmonary hemorrhage occurred in the loading-dose group. CONCLUSION: Loading-dose DAPT initiated within 48 hours was associated with reduced early motor deterioration and better functional outcomes, but larger multicenter trials are needed to confirm efficacy and safety. Trial registration: UMIN000058468; retrospectively registered.