Cytochrome P450 2C19 polymorphism, suboptimal reperfusion and all-cause mortality in patients with acute myocardial infarction

Cardiology. 2010;117(2):81-7. doi: 10.1159/000320093. Epub 2010 Oct 6.

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: The study 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / mortality*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Female
  • Follow-Up Studies
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction* / genetics
  • Myocardial Infarction* / mortality
  • Myocardial Infarction* / therapy
  • Platelet Aggregation Inhibitors / therapeutic use
  • Predictive Value of Tests
  • Prevalence
  • Risk Factors
  • Stents / statistics & numerical data*
  • Survival Analysis
  • Thrombosis / mortality
  • Thrombosis / prevention & control
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine