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 & 1 others Kyung Yul Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)356-364
Number of pages9
JournalJournal of Stroke
Volume19
Issue number3
DOIs
Publication statusPublished - 2017 Sep 1

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clopidogrel
Secondary Prevention
Cytochrome P-450 Enzyme System
Stroke
Genotype
Platelet Aggregation Inhibitors
Confidence Intervals
triflusal
Therapeutics
Random Allocation

Keywords

  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Stroke
  • Triflusal

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Effects of triflusal and clopidogrel on the secondary prevention of stroke based on cytochrome p450 2c19 genotyping. / Han, Sang Won; Kim, Yong Jae; Ahn, Seong Hwan; Seo, Woo Keun; Yu, Sungwook; Oh, Seung Hun; Nam, Hyo Suk; Choi, Hye Yeon; Yoon, Sung Sang; Kim, Seo Hyun; Lee, Jong Yun; Lee, Jun Hong; Hwang, Yang Ha; Lee, Kee Ook; Jung, Yo Han; Lee, Jun; Sohn, Sung Il; Kim, Youn Nam; Lee, Kyung A.; Bushnell, Cheryl D.; Lee, Kyung Yul.

In: Journal of Stroke, Vol. 19, No. 3, 01.09.2017, p. 356-364.

Research output: Contribution to journalArticle

Han, SW, Kim, YJ, Ahn, SH, Seo, WK, Yu, S, Oh, SH, Nam, HS, Choi, HY, Yoon, SS, Kim, SH, Lee, JY, Lee, JH, Hwang, YH, Lee, KO, Jung, YH, Lee, J, Sohn, SI, Kim, YN, Lee, KA, Bushnell, CD & Lee, KY 2017, 'Effects of triflusal and clopidogrel on the secondary prevention of stroke based on cytochrome p450 2c19 genotyping', Journal of Stroke, vol. 19, no. 3, pp. 356-364. https://doi.org/10.5853/jos.2017.01249
Han, Sang Won ; Kim, Yong Jae ; Ahn, Seong Hwan ; Seo, Woo Keun ; Yu, Sungwook ; Oh, Seung Hun ; Nam, Hyo Suk ; Choi, Hye Yeon ; Yoon, Sung Sang ; Kim, Seo Hyun ; Lee, Jong Yun ; Lee, Jun Hong ; Hwang, Yang Ha ; Lee, Kee Ook ; Jung, Yo Han ; Lee, Jun ; Sohn, Sung Il ; Kim, Youn Nam ; Lee, Kyung A. ; Bushnell, Cheryl D. ; Lee, Kyung Yul. / Effects of triflusal and clopidogrel on the secondary prevention of stroke based on cytochrome p450 2c19 genotyping. In: Journal of Stroke. 2017 ; Vol. 19, No. 3. pp. 356-364.
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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.",
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AU - Han, Sang Won

AU - Kim, Yong Jae

AU - Ahn, Seong Hwan

AU - Seo, Woo Keun

AU - Yu, Sungwook

AU - Oh, Seung Hun

AU - Nam, Hyo Suk

AU - Choi, Hye Yeon

AU - Yoon, Sung Sang

AU - Kim, Seo Hyun

AU - Lee, Jong Yun

AU - Lee, Jun Hong

AU - Hwang, Yang Ha

AU - Lee, Kee Ook

AU - Jung, Yo Han

AU - Lee, Jun

AU - Sohn, Sung Il

AU - Kim, Youn Nam

AU - Lee, Kyung A.

AU - Bushnell, Cheryl D.

AU - Lee, Kyung Yul

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N2 - 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.

AB - 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.

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