Dual Antiplatelet Therapy in Acute Ischemic Stroke: A 2‐Time‐Window Study of CYP2C19 Genotypes and Functional Outcomes

Background Carriers of CYP2C19 loss‐of‐function alleles (LoFA) exhibit reduced metabolism of clopidogrel, potentially compromising the efficacy of dual antiplatelet therapy (DAPT) in acute ischemic stroke. We aimed to distinguish the impact of initial antiplatelet regimens from the discharge deescalation on functional outcomes. Methods The retrospective cohort study linked the prospective stroke registry with the Taiwan Precision Medicine Initiative biobank. Patients with mild to moderate acute ischemic stroke (National Institutes of Health Stroke Scale score ≤10) were included. Favorable outcomes (modified Rankin Scale score ≤1) of 2 windows were analyzed: (1) the acute window (≤48 hours), assessing outcomes at discharge, and (2) the deescalation window (discharge), assessing outcomes at 90 days. Results Among 741 patients, 463 (62.5%) were LoFA carriers. In the acute window, genotype was not associated with favorable outcomes; clinical severity (age, initial National Institutes of Health Stroke Scale score) was the dominant predictor. However, in the deescalation window, in the overall cohort, DAPT with aspirin and clopidogrel at discharge was independently associated with favorable outcomes at 90 days (odds ratio [OR], 2.34 [95% CI, 1.16–4.74]; P =0.018). Stratified analysis revealed that this benefit was driven primarily by LoFA carriers, in whom DAPT with aspirin and clopidogrel at discharge was independently associated with favorable outcomes (OR, 2.74 [95% CI, 1.17–6.38]; P =0.020). However, this association was attenuated in propensity score‐matched analyses, and there was no interaction between CYP2C19 LoFA carrier status and DAPT with aspirin and clopidogrel on favorable outcomes at 90 days. Conclusions CYP2C19 genotype did not predict early neurological deterioration. The potential long‐term clinical benefit of maintaining DAPT with aspirin and clopidogrel at discharge for LoFA carriers requires confirmation in adequately powered randomized trials.