Clinical Implications of Platelet Reactivity after Antiplatelet Initiation in Patients with Acute Ischaemic Stroke

Background: Antiplatelet therapy is a cornerstone of acute ischaemic stroke management, but high on-treatment platelet reactivity (HOTPR) may undermine its efficacy. This study aimed to assess platelet reactivity and HOTPR status during the acute phase of ischaemic stroke following antiplatelet initiation, and to explore their associations with stroke outcomes in a Malaysian cohort. Methods: This prospective, observational study enrolled 198 patients with acute ischaemic stroke admitted to Sarawak General Hospital. Platelet reactivity was measured at baseline and on Days 1 and 3 post-antiplatelet therapy using Multiplate® Analyser. HOTPR was defined by ASPItest (> 30 U) or ADPtest (> 46 U) values. The primary outcome was recurrent stroke at one year, while secondary outcomes included early neurological deterioration (END), poor functional outcome (mRS ≥ 2) at three months, and all-cause mortality at one year. Cox and logistic regression models adjusted for demographic and clinical covariates were applied. Results: The mean age of participants was 59.8 years, with 66.7% being male. At one year, 9.1% experienced recurrent stroke and 9.6% had died, 9.1% experience END during admission, and 21.6% had mRS ≥ 2 at three months. Platelet reactivity and HOTPR status on Days 1 and 3 did not significantly predict recurrent stroke at one year or END. However, higher ADPtest values [OR 1.05 (95% CI 1.00, 1.09), p  = 0.037], clopidogrel HOTPR on Days 1 and 3 [OR 20.99 (95% CI 1.53, 7089.91), p  = 0.017; OR 16.58 (95% CI 1.57, 24326.82), p  = 0.017], and sustained clopidogrel HOTPR on both Days 1 and 3 [OR 45.25 (95% CI 2.34, 21861.76), p  = 0.007] were significantly associated with poor functional outcomes at three months. Aspirin-treated patients who normalised on-treatment platelet reactivity by Day 3 were significantly associated with lower mortality risk [HR 0.09 (95% CI 0.001–0.85), p  = 0.031]. Conclusion: Platelet reactivity and HOTPR measured using Multiplate® Analyser were not significantly associated with recurrent stroke or END, though they showed some predictive value for poor functional outcomes and mortality. Further investigation into the role of platelet reactivity monitoring in in acute stroke management is warranted.