Efficacy of Dual Antiplatelet therapy after Ischemic Stroke According to hsCRP Levels and CYP2C19 Genotype.

Background: Both high-sensitive C-reactive protein (hsCRP) and CYP2C19 genotypes are independent predictors of clinical outcomes after ischemic stroke. We aim to evaluate the association of CYP2C19 loss-of-function alleles (LoFA) carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels using the CHANCE trial.

Methods: Subjects with both of CYP2C19 major alleles information (*2, *3, and *17) and hsCRP measurements were enrolled from the prespecified subgroup. CYP2C19 LoFA carriers were defined as patients with either*2 or *3 allele. Cox proportional hazards models were used to assess the interaction of CYP2C19 LoFA carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels. The primary outcome was recurrent stroke within 90 days.

Results: Among 2801 patients, 1646 (58.8%) were LoFA carriers, and 922 (32.9%) had elevated hsCRP. In patients with non-elevated hsCRP, there was a significant interaction effect between CYP2C19 LoFA carrying status and dual/single antiplatelet regimens for prevention of recurrent stroke and combined vascular events (p =0.048, 0.048, respectively), but, not in patients with elevated hsCRP (p =0.502, 0.472, respectively). Only among patients with non-elevated hsCRP and non-carrier of CYP2C19 LoFA, dual antiplatelets significantly reduced the risk of recurrent stroke compared with aspirin alone (hazard ratio= 0.44 [0.26-0.74], p=0.003). No significant differences in bleeding were found.

Conclusions: Non-elevated hsCRP and non-carrier of CYP2C19 LoFA may predict a better response to dual antiplatelet therapy in reducing stroke recurrence and composite vascular events for patients with minor stroke and high-risk TIA.

Trial registration: clinicaltrials.gov Identifier: NCT00979589.