Relationship Between Statin Type and Responsiveness to Clopidogrel in Patients Treated with Percutaneous Coronary Intervention: A Subgroup Analysis of the CILON-T Trial

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.