Effects of Triflusal and Clopidogrel on the Secondary Prevention of Stroke Based on Cytochrome P450 2C19 Genotyping

Sang Won Han, Yong-Jae Kim, Seong Hwan Ahn, Woo-Keun Seo, Sungwook Yu, Seung-Hun Oh, Hyo Suk Nam, Hye-Yeon Choi, Sung Sang Yoon, Seo Hyun Kim, Jong Yun Lee, Jun Hong Lee, Yang-Ha Hwang, Kee Ook Lee, Yo Han Jung, Jun Lee, Sung-Il Sohn, Youn Nam Kim, Kyung-A Lee, Cheryl D Bushnell, Kyung-Yul Lee, Sang Won Han, Yong-Jae Kim, Seong Hwan Ahn, Woo-Keun Seo, Sungwook Yu, Seung-Hun Oh, Hyo Suk Nam, Hye-Yeon Choi, Sung Sang Yoon, Seo Hyun Kim, Jong Yun Lee, Jun Hong Lee, Yang-Ha Hwang, Kee Ook Lee, Yo Han Jung, Jun Lee, Sung-Il Sohn, Youn Nam Kim, Kyung-A Lee, Cheryl D Bushnell, Kyung-Yul Lee

Abstract

Background and purpose: To compare the efficacy and safety of antiplatelet agents for the secondary prevention of ischemic stroke based on cytochrome P450 2C19 (CYP2C19) polymorphisms.

Methods: This study was a prospective, multicenter, randomized, parallel-group, open-label, blind genotype trial. First time non-cardiogenic ischemic stroke patients were enrolled and screened within 30 days. Participants were randomized to receive either triflusal or clopidogrel for secondary stroke prevention. The primary outcome was the time from randomization to first recurrent ischemic stroke or hemorrhagic stroke.

Results: The required sample size was 1,080 but only 784 (73%) participants were recruited. In patients with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of recurrent stroke among those who received triflusal treatment was 2.9% per year, which was not significantly different from those who received clopidogrel treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.60-2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke in patients with a good CYP2C19 genotype was 1.6% per year, which was not significantly different from those with a poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26-1.79).

Conclusions: Whilst there were no significant differences between the treatment groups in the rates of stroke recurrence, major vascular events, or coronary revascularization, the efficacy of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype status remains unclear.

Keywords: Clopidogrel; Cytochrome P-450 CYP2C19; Stroke; Triflusal.

Conflict of interest statement

The authors have no financial conflicts of interest.

Figures

Figure 1.
Figure 1.
Design of the MAESTRO study. MAESTRO, stroke based on cytochrome P450 2C19 genotyping. *Withdrawal of consent before genotyping.
Figure 2.
Figure 2.
Differences in the primary endpoint according to CYP2C19 geno-type and treatment. CYP2C19, cytochrome P450 2C19; CI, confidence interval.

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