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The Impact of Cyctochrome 2C19 Genotype on Platelet Function in Acute and Chronic phase of Clopidogrel Therapy after Percutaneous Coronary Intervention
동아대학교병원 순환기내과¹, 임상시험센터²
장홍철¹ ² , 김무현¹ ², 김성환², 곽용철², 백희경¹, 조용락¹, 박경일¹, 박종성¹, 박태호¹, 김영대¹
Introduction: Carriers of loss of function (LOF) CYP2C19 allele on clopidogrel therapy are related to diminished platelet inhibition and higher rate of clinical event. There is few comparative study to show the relationship between platelet function tests and time dependency according to the CYP2C19 LOF allele among patients undergoing percutaneous coronary intervention. Materials and Methods: We enrolled 199 consecutive patients, either on chronic clopidogrel maintenance therapy (n=99, chronic group) or received a 300 mg or 600mg clopidogrel loading dose (n= 100, acute group). Platelet function was assessed by light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA). Results: Percentage of carriers of LOF allele was not different in both group (54/100 in acute vs 61/99 in chronic group, p=0.518). In both treatment groups, carriers of LOF gene was associated with higher on treatment platelet reactivity (HPR) in maximal platelet aggregation by LTA assay (acute group: 32.6±17.8% vs 45.1±16.8%, p=0.001, chronic group: 39.1±18.1% vs 47.1±14.1%, p=0.024), but MEA assay showed significant difference only in acute group (acute group: 24.7±11.3% vs 31.9±16.3%, p=0.014, chronic group: 39.1±18.1% vs 44.2±21.2%, p=0.207). Receiver operating characteristic (ROC) curve analysis according to the CYP2C19 LOF allele showed that LTA and MEA were significant predictors of carrier state [AUC 0.694 (95% CI : 0.591-0.785, p=0.003) vs AUC 0.634 (95% CI : 0.529-0.731, p=0.018)] in acute group (left figure), but only LTA were significant predictor of carrier state [AUC 0.638 (95%CI 0.536-0.732, p=0.013 vs AUC 0.581 (95% CI 0.477-0.679, p=0.165)] in chronic group (right figure). Conclusion: Our data suggested that the impact of carriers of CYP2C19 LOF allele on platelet function test was greater in acute phase but less evident in chronic phase. Also MEA assay did not show the power to predict the carrier status of LOF gene in chronic phase.
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