Impact of CYP2C19 Polymorphism and Proton Pump Inhibitors on Platelet Reactivity to Clopidogrel and Clinical Outcomes Following Stent Implantation
Autor: | Michio Mizobe, Koichi Kaikita, Seiji Hokimoto, Kazuko Nakagawa, Tomonori Akasaka, Yuichiro Arima, Hisao Ogawa |
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Rok vydání: | 2014 |
Předmět: |
Blood Platelets
Male Acute coronary syndrome medicine.medical_specialty Ticlopidine Genotype Platelet Aggregation medicine.drug_class medicine.medical_treatment Rabeprazole Proton-pump inhibitor CYP2C19 Gastroenterology Percutaneous Coronary Intervention Internal medicine medicine Humans Drug Interactions Aged Polymorphism Genetic business.industry Percutaneous coronary intervention Hematology Middle Aged Drug interaction medicine.disease Clopidogrel Cytochrome P-450 CYP2C19 Cardiovascular Diseases Cardiology Female Stents business medicine.drug |
Zdroj: | Thrombosis Research. 133:599-605 |
ISSN: | 0049-3848 |
Popis: | The response to clopidogrel, and some kind of the drug interaction are multifactorial.We enrolled 174 consecutive patients and determined CYP2C19 genotypes, measured platelet aggregation, and assessed the relationship between CYP2C19 genotype and platelet reactivity 24hours after clopidogrel administration, and the risk of cardiovascular events over 18months follow-up. A sub analysis examined the impact of rabeprazole, a proton pump inhibitor (PPI) less affected by CYP2C19. The CYP2C19 genotype was extensive metabolizer (EM) in 36%, intermediate metabolizer (IM) in 45%, and poor metabolizer (PM) in 19%. Platelet reactivity was significantly lower in the EM group than in the IM and PM groups (EM, IM, PM: 3560±1404, 4203±1302, 5084±1007AU•min, P0.05). The cardiovascular event rate was higher in the IM and PM groups than in the EM group (12.7% and 12.5% vs 1.6%; Hazard ratio for IM 10.6, P=0.029; for PM 11.3, P=0.040). No differences were seen between patients taking (N=50) and not taking (N=124) rabeprazole in residual platelet aggregation (4407±1360 vs 4048±1394, AU•min, P=0.2782), or in cardiovascular events (10.0% vs 8.1%, HR 0.97, P=0.97).CYP2C19 genotype is associated with an increased risk of cardiovascular events following stent implantation in Japanese patients. |
Databáze: | OpenAIRE |
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