title: Platelet reactivity and clinical outcomes in patients using CYP3A4-metabolized statins with clopidogrel in percutaneous coronary intervention.
abstract: Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel's anti-aggregatory effect on platelets. We aimed to assess the impact of concomitant CYP3A4-metabolized statin and clopidogrel use on antiplatelet activity and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We enrolled 1187 patients from the HOST-ASSURE trial with platelet reactivity unit (PRU) values at both baseline and 1 month. Patients were assigned to the CYP3A4-metabolized statin group (group A, n = 725) or non-CYP3A4-metabolized statin group (group B, n = 462) according to type of statin used. Co-primary outcomes were the differences between PRU at baseline and 1 month and the composite of cardiovascular death, recurrent myocardial infarction, stent thrombosis, revascularization, and cerebrovascular accident. We found that follow-up PRU values did not change in group A and decreased significantly in group B (mean difference: -15 ± 79, p < 0.001) in both the crude and matched cohorts. Patients with a high PRU value at baseline, irrespective of statin type, had a significant reduction in mean PRU difference (group A, -62 ± 78, p < 0.001; group B, -59 ± 69, p < 0.001) in both the crude and matched cohorts. The composite of clinical events did not differ between groups in either cohort. CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. However, they do not inhibit clopidogrel's antiplatelet effect in patients with high platelet reactivity or increase clinical events in patients following PCI.
authors.affiliation: Department of Cardiology, Pusan National University Hospital, 1-10 Ami-dong Seo-gu, Busan, 602-739, Republic of Korea.|Medical Research Institute, Pusan National University Hospital, Busan, South Korea.
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Cardiology, Pusan National University Hospital, 1-10 Ami-dong Seo-gu, Busan, 602-739, Republic of Korea. cks@pusan.ac.kr.|Medical Research Institute, Pusan National University Hospital, Busan, South Korea. cks@pusan.ac.kr.
authors.forename: Kwang Soo
authors.initials: KS
authors.lastname: Cha
authors.affiliation: Department of Cardiology, Pusan National University Hospital, 1-10 Ami-dong Seo-gu, Busan, 602-739, Republic of Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Pusan National University Hospital, 1-10 Ami-dong Seo-gu, Busan, 602-739, Republic of Korea.
authors.forename: Jun-Hyok
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Department of Cardiology, Pusan National University Hospital, 1-10 Ami-dong Seo-gu, Busan, 602-739, Republic of Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Cardiology, Pusan National University Hospital, 1-10 Ami-dong Seo-gu, Busan, 602-739, Republic of Korea.
authors.forename: Han Cheol
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Pusan National University Hospital, 1-10 Ami-dong Seo-gu, Busan, 602-739, Republic of Korea.
authors.forename: Taek Jong
authors.initials: TJ
authors.lastname: Hong
authors.affiliation: Seoul National University Hospital, Seoul, South Korea.
authors.forename: Hyo Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D057216:Propensity Score; D011446:Prospective Studies; D056910:Republic of Korea; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Clinical outcomes; Clopidogrel; Cytochrome P 3A4; Platelet reactivity; Statin