Efficacy of dual antiplatelet therapy after ischemic stroke according to hsCRP levels and CYP2C19 genotype

Abstract

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 2,801 patients, 1,646 (58.8%) were LoFA carriers, and 922 (32.9%) had elevated hsCRP. In patients with nonelevated 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 = .048, .048, respectively), but, not in patients with elevated hsCRP (P = .502, .472, respectively). Only among patients with nonelevated hsCRP and noncarrier 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 = .003). No significant differences in bleeding were found.

Conclusions

Nonelevated hsCRP and noncarrier 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