Relationship between statin type and responsiveness to clopidogrel in patients treated with percutaneous coronary intervention

A subgroup analysis of the CILON-T trial

Jung Won Suh, Myung Jin Cha, Seung Pyo Lee, In Ho Chae, Jang Ho Bae, Taek Geun Kwon, Jang Whan Bae, Myeong Chan Cho, Seung-Woon Rha, Hyo Soo Kim

Research output: Contribution to journalArticle

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Abstract

Aim: To compare the responsiveness to clopidogrel in patients who were prescribed two different types of statins, atorvastatin vs. rosuvastatin, following percutaneous coronary intervention. Methods: A total of 915 patients were randomized according to the antiplatelet therapy strategy in the CILON-T trial. In this subgroup analysis, we included patients who took atorvastatin (20 mg/day, n=295) or rosuvastatin (10 mg/day, n=261) during the entire study period and underwent measurement of the P2Y12 reaction unit (PRU) values at both discharge and six months. We compared the P2Y12 reaction unit (PRU) values at six months and investigated the relationship between the genotypes of cytochrome P450 (CYP) 3A4, 3A5 and 2C19 with the PRU values at six months in both groups. Results: The baseline characteristics did not differ between the groups. There were no significant differences in the PRU values at discharge (atorvastatin 221.0±87.3 vs. rosuvastatin 217.1±84.7, p= 0.59). However, the rosuvastatin group had higher PRU values than the atorvastatin group at six months (atorvastatin 226.4±79.3 vs. rosuvastatin 241.5±88.2, p= 0.033). In the genotype analysis, the number of CYP2C19 loss-of-function (LOF) alleles (*2 or *3) was positively associated with a higher PRU value in both statin groups, and there were no significant interactions regarding the PRU values between the number of CYP 2C19 LOF alleles and the type of statin (p for interaction= 0.56). In the multivariate analysis, the use of rosuvastatin was a significant predictor of a PRU value of >273 (the highest tertile) (OR 1.67, 95% confidence interval 1.05-2.65, p=0.031). Conclusions: Rosuvastatin is associated with high on-treatment platelet reactivity compared with atorvastatin following the coadministration of clopidogrel for six months. Further studies are therefore warranted to clarify the mechanism underlying this relationship.

Original languageEnglish
Pages (from-to)140-150
Number of pages11
JournalJournal of Atherosclerosis and Thrombosis
Volume21
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

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clopidogrel
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Percutaneous Coronary Intervention
Cytochrome P-450 CYP3A
Alleles
Genotype
Platelets
Rosuvastatin Calcium
Cytochrome P-450 Enzyme System
Atorvastatin Calcium

Keywords

  • Atorvastatin
  • Clopidogrel
  • Platelet function
  • Rosuvastatin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Internal Medicine
  • Biochemistry, medical

Cite this

Relationship between statin type and responsiveness to clopidogrel in patients treated with percutaneous coronary intervention : A subgroup analysis of the CILON-T trial. / Suh, Jung Won; Cha, Myung Jin; Lee, Seung Pyo; Chae, In Ho; Bae, Jang Ho; Kwon, Taek Geun; Bae, Jang Whan; Cho, Myeong Chan; Rha, Seung-Woon; Kim, Hyo Soo.

In: Journal of Atherosclerosis and Thrombosis, Vol. 21, No. 2, 01.01.2014, p. 140-150.

Research output: Contribution to journalArticle

Suh, Jung Won ; Cha, Myung Jin ; Lee, Seung Pyo ; Chae, In Ho ; Bae, Jang Ho ; Kwon, Taek Geun ; Bae, Jang Whan ; Cho, Myeong Chan ; Rha, Seung-Woon ; Kim, Hyo Soo. / Relationship between statin type and responsiveness to clopidogrel in patients treated with percutaneous coronary intervention : A subgroup analysis of the CILON-T trial. In: Journal of Atherosclerosis and Thrombosis. 2014 ; Vol. 21, No. 2. pp. 140-150.
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abstract = "Aim: To compare the responsiveness to clopidogrel in patients who were prescribed two different types of statins, atorvastatin vs. rosuvastatin, following percutaneous coronary intervention. Methods: A total of 915 patients were randomized according to the antiplatelet therapy strategy in the CILON-T trial. In this subgroup analysis, we included patients who took atorvastatin (20 mg/day, n=295) or rosuvastatin (10 mg/day, n=261) during the entire study period and underwent measurement of the P2Y12 reaction unit (PRU) values at both discharge and six months. We compared the P2Y12 reaction unit (PRU) values at six months and investigated the relationship between the genotypes of cytochrome P450 (CYP) 3A4, 3A5 and 2C19 with the PRU values at six months in both groups. Results: The baseline characteristics did not differ between the groups. There were no significant differences in the PRU values at discharge (atorvastatin 221.0±87.3 vs. rosuvastatin 217.1±84.7, p= 0.59). However, the rosuvastatin group had higher PRU values than the atorvastatin group at six months (atorvastatin 226.4±79.3 vs. rosuvastatin 241.5±88.2, p= 0.033). In the genotype analysis, the number of CYP2C19 loss-of-function (LOF) alleles (*2 or *3) was positively associated with a higher PRU value in both statin groups, and there were no significant interactions regarding the PRU values between the number of CYP 2C19 LOF alleles and the type of statin (p for interaction= 0.56). In the multivariate analysis, the use of rosuvastatin was a significant predictor of a PRU value of >273 (the highest tertile) (OR 1.67, 95{\%} confidence interval 1.05-2.65, p=0.031). Conclusions: Rosuvastatin is associated with high on-treatment platelet reactivity compared with atorvastatin following the coadministration of clopidogrel for six months. Further studies are therefore warranted to clarify the mechanism underlying this relationship.",
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T2 - A subgroup analysis of the CILON-T trial

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AU - Cha, Myung Jin

AU - Lee, Seung Pyo

AU - Chae, In Ho

AU - Bae, Jang Ho

AU - Kwon, Taek Geun

AU - Bae, Jang Whan

AU - Cho, Myeong Chan

AU - Rha, Seung-Woon

AU - Kim, Hyo Soo

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N2 - Aim: To compare the responsiveness to clopidogrel in patients who were prescribed two different types of statins, atorvastatin vs. rosuvastatin, following percutaneous coronary intervention. Methods: A total of 915 patients were randomized according to the antiplatelet therapy strategy in the CILON-T trial. In this subgroup analysis, we included patients who took atorvastatin (20 mg/day, n=295) or rosuvastatin (10 mg/day, n=261) during the entire study period and underwent measurement of the P2Y12 reaction unit (PRU) values at both discharge and six months. We compared the P2Y12 reaction unit (PRU) values at six months and investigated the relationship between the genotypes of cytochrome P450 (CYP) 3A4, 3A5 and 2C19 with the PRU values at six months in both groups. Results: The baseline characteristics did not differ between the groups. There were no significant differences in the PRU values at discharge (atorvastatin 221.0±87.3 vs. rosuvastatin 217.1±84.7, p= 0.59). However, the rosuvastatin group had higher PRU values than the atorvastatin group at six months (atorvastatin 226.4±79.3 vs. rosuvastatin 241.5±88.2, p= 0.033). In the genotype analysis, the number of CYP2C19 loss-of-function (LOF) alleles (*2 or *3) was positively associated with a higher PRU value in both statin groups, and there were no significant interactions regarding the PRU values between the number of CYP 2C19 LOF alleles and the type of statin (p for interaction= 0.56). In the multivariate analysis, the use of rosuvastatin was a significant predictor of a PRU value of >273 (the highest tertile) (OR 1.67, 95% confidence interval 1.05-2.65, p=0.031). Conclusions: Rosuvastatin is associated with high on-treatment platelet reactivity compared with atorvastatin following the coadministration of clopidogrel for six months. Further studies are therefore warranted to clarify the mechanism underlying this relationship.

AB - Aim: To compare the responsiveness to clopidogrel in patients who were prescribed two different types of statins, atorvastatin vs. rosuvastatin, following percutaneous coronary intervention. Methods: A total of 915 patients were randomized according to the antiplatelet therapy strategy in the CILON-T trial. In this subgroup analysis, we included patients who took atorvastatin (20 mg/day, n=295) or rosuvastatin (10 mg/day, n=261) during the entire study period and underwent measurement of the P2Y12 reaction unit (PRU) values at both discharge and six months. We compared the P2Y12 reaction unit (PRU) values at six months and investigated the relationship between the genotypes of cytochrome P450 (CYP) 3A4, 3A5 and 2C19 with the PRU values at six months in both groups. Results: The baseline characteristics did not differ between the groups. There were no significant differences in the PRU values at discharge (atorvastatin 221.0±87.3 vs. rosuvastatin 217.1±84.7, p= 0.59). However, the rosuvastatin group had higher PRU values than the atorvastatin group at six months (atorvastatin 226.4±79.3 vs. rosuvastatin 241.5±88.2, p= 0.033). In the genotype analysis, the number of CYP2C19 loss-of-function (LOF) alleles (*2 or *3) was positively associated with a higher PRU value in both statin groups, and there were no significant interactions regarding the PRU values between the number of CYP 2C19 LOF alleles and the type of statin (p for interaction= 0.56). In the multivariate analysis, the use of rosuvastatin was a significant predictor of a PRU value of >273 (the highest tertile) (OR 1.67, 95% confidence interval 1.05-2.65, p=0.031). Conclusions: Rosuvastatin is associated with high on-treatment platelet reactivity compared with atorvastatin following the coadministration of clopidogrel for six months. Further studies are therefore warranted to clarify the mechanism underlying this relationship.

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