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Cytochrome P450 2C19 Polymorphism, Suboptimal Reperfusion and All-Cause Mortality in Patients with Acute Myocardial Infarction

Małek Ł.A.a · Przyłuski J.a · Śpiewak M.b · Kłopotowski M.a · Kostrzewa G.c · Kruk M.b · Płoski R.c · Witkowski A.a · Rużyłło W.d
Departments of aInterventional Cardiology and Angiology, and bCoronary Artery Disease and Structural Heart Diseases, Institute of Cardiology, cDepartment of Medical Genetics, Centre of Biostructure, Medical University of Warsaw, and dInstitute of Cardiology, Warsaw, Poland Cardiology 2010;117:81–87 (DOI:10.1159/000320093)

Abstract

Objectives: To determine whether the 681 G>A (*2) polymorphism of cytochrome P450 (CYP2C19) is related to suboptimal reperfusion and mortality in patients with acute myocardial infarction (AMI) pretreated with clopidogrel. Methods: Thestudy included 276 consecutive patients with AMI in whom percutaneous coronary intervention (PCI) with stenting was attempted. Four-year follow-up for all-cause mortality was obtained. Results: There were 15 failed procedures (5.4%). In the remaining 261 patients, suboptimal reperfusion (post-PCI TIMI flow <3) was observed in 12.6% of the cases. There were 56 carriers (50 heterozygous and 6 homozygous) of CYP2C19*2. The prevalence of carriers in patients with suboptimal flow was 39.4% in comparison to 18.9% in the other patients (p = 0.01). Independent predictors of suboptimal reperfusion were initial TIMI flow ≤1 (OR = 5.9, 95% CI 2.2–16.2, p = 0.001) and CYP2C19*2 (OR = 2.9, 95% CI 1.3–6.6, p = 0.01). Thirty patients died during follow-up (11.5%). Four-year mortality tended to be higher in carriers of CYP2C19*2 (17.9%) versus non-carriers (9.8%; p = 0.09), but the only independent predictors of death were age (HR = 2.0, 95% CI = 1.4–2.8, p = 0.0001) and suboptimal reperfusion (HR = 3.6, 95% CI 1.5–8.8, p = 0.004). Conclusions: The CYP2C19*2 allele is an independent predictor of suboptimal reperfusion in patients with AMI undergoing PCI with stenting after pretreatment with clopidogrel and may increase the risk of all-cause mortality.

 

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