Clinical implications of platelet reactivity after antiplatelet initiation in patients with acute ischaemic stroke.

Background: High on-treatment platelet reactivity (HOTPR) may undermine the efficacy of antiplatelet therapy in acute stroke. This study aimed to assess platelet reactivity and HOTPR status during the acute phase of ischaemic stroke following antiplatelet initiation, and to determine their associations with stroke outcomes in a Malaysian cohort.

Methods: This prospective, observational study enrolled patients with acute ischaemic stroke at 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 clinical covariates were used, with Firth's correction applied for rare events and model non-convergence.

Results: A total of 198 participants were enrolled, with a mean age of 59.8 years; 66.7% were male. At one year, 9.1% experienced recurrent stroke, 9.6% had died, 9.2% experienced END during admission, and 21.6% had mRS ≥ 2 at three months. HOTPR rates decreased by Day 3 (aspirin: Day 1 20.0% to Day 3 6.6%; clopidogrel: 50.5-28.0%), with persistent HOTPR in 11.8% (aspirin) and 39.2% (clopidogrel). Some initially normal responders developed HOTPR by Day 3 (aspirin 5.4%, clopidogrel 16.3%). Platelet reactivity and HOTPR status on Days 1 and 3 were not significantly associated with recurrent stroke at one year or END. However, higher ADPtest values on Day 1 [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 persistent clopidogrel HOTPR on both days [OR 45.25 (95% CI 2.34, 21861.76), p = 0.007] were significantly associated with poor functional outcomes.

Conclusion: Platelet reactivity and HOTPR status were not associated with recurrent stroke and END. However, higher ADPtest values and clopidogrel-related HOTPR were associated with poor functional outcomes. Further studies are needed to evaluate the clinical utility of platelet reactivity monitoring in acute stroke management.