Comparison Between Clopidogrel and Prasugrel Associated With CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population.


Journal

Circulation journal : official journal of the Japanese Circulation Society
ISSN: 1347-4820
Titre abrégé: Circ J
Pays: Japan
ID NLM: 101137683

Informations de publication

Date de publication:
25 08 2020
Historique:
pubmed: 28 7 2020
medline: 14 10 2021
entrez: 28 7 2020
Statut: ppublish

Résumé

The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85-4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10-9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14-3.26, P=0.62). Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.

Sections du résumé

BACKGROUND
The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85-4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10-9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14-3.26, P=0.62).
CONCLUSIONS
Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.

Identifiants

pubmed: 32713878
doi: 10.1253/circj.CJ-20-0254
doi:

Substances chimiques

Platelet Aggregation Inhibitors 0
Clopidogrel A74586SNO7
CYP2C19 protein, human EC 1.14.14.1
Cytochrome P-450 CYP2C19 EC 1.14.14.1
Prasugrel Hydrochloride G89JQ59I13

Types de publication

Comparative Study Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1575-1581

Auteurs

Yuichi Sawayama (Y)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Takashi Yamamoto (T)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Yukinori Tomita (Y)

Department of Cardiovascular Medicine, Toyosato Hospital.

Kohei Asada (K)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Noriaki Yagi (N)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Megumi Fukuyama (M)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Akashi Miyamoto (A)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Hiroshi Sakai (H)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Tomoya Ozawa (T)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

Tetsuichiro Isono (T)

Department of Pharmacy, Shiga University of Medical Science.

Daiki Hira (D)

Department of Pharmacy, Shiga University of Medical Science.
College of Pharmaceutical Sciences, Ritsumeikan University.

Tomohiro Terada (T)

Department of Pharmacy, Shiga University of Medical Science.

Minoru Horie (M)

Center for Epidemiologic Research in Asia, Shiga University of Medical Science.

Yoshihisa Nakagawa (Y)

Department of Cardiovascular Medicine, Shiga University of Medical Science.

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Classifications MeSH