클로피도그렐 치료에서 CYP2C19 유전자 다형성에 따른 흡연과 뇌졸중 재발 관련성

Abstract

Background:To perform a subgroup analysis of the MAESTRO trial to explore the relationship between smoking status with regard to Cytochrome P450 2C19 (CYP2C19) polymorphisms and stroke recurrence in patients who underwent clopidogrel treatment. Methods:Male patients who underwent VerifyNow assay and CYP2C19 genotyping were selected from the MAESTRO study. CYP2C19 ultrarapid metabolizer or extensive metabolizer and intermediate/unknown metabolizer or poor metabolizer was allocated into the good genotype and poor genotype groups, respectively. Results:Of 393 patients who underwent clopidogrel treatment in the MAESTRO trial, 182 (46.3%) male patients were chosen for this study. The median follow-up duration was 3.0 years (range, 0-4.5). Ninety-five patients (52%) were current smokers. Seventy (38.5%) patients had a good genotype for clopidogrel metabolism and 112 (61.5%) had a poor genotype. Seven (3.8%) patients had a recurrent ischemic stroke. Though there was no significant difference, a trend toward lower recurrent stroke and a major vascular event was observed in the good genotype group among current smokers. The risk of recurrent stroke was 0% and 8.5% in the good genotype and poor genotype groups, respectively (P=0.086). The risk of a major vascular event was 0% and 10.2% in the good genotype and poor genotype groups (P=0.051). In the nonsmokers, there was no reduction in risk for recurrent stroke (0% vs 3.8%, P=0.368) and a major vascular event (2.9% vs 3.8%, P=0.663) in the good genotype group. Conclusions: Smoking status may modify the effect of clopidogrel treatment on outcome according to CYP2C19 polymorphisms.