Comparison Between Clopidogrel and Prasugrel Associated With CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population.
Aged
Aged, 80 and over
Alleles
Clopidogrel
/ adverse effects
Coronary Thrombosis
/ chemically induced
Cytochrome P-450 CYP2C19
/ genetics
Female
Follow-Up Studies
Genotype
Hemorrhage
/ chemically induced
Humans
Japan
/ epidemiology
Loss of Function Mutation
Male
Middle Aged
Myocardial Infarction
/ chemically induced
Percutaneous Coronary Intervention
/ adverse effects
Platelet Aggregation Inhibitors
/ adverse effects
Prasugrel Hydrochloride
/ adverse effects
Retrospective Studies
Stroke
/ chemically induced
Treatment Outcome
CYP2C19
Clopidogrel
P2Y12 inhibitor
Percutaneous coronary intervention
Prasugrel
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
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