Relation of Cytochrome P450 2C19 Loss-Of-Function Polymorphism to Occurrence of Drug-Eluting Coronary Stent Thrombosis

Am J Cardiol. 2009 Mar 15;103(6):806-11. doi: 10.1016/j.amjcard.2008.11.048. Epub 2009 Jan 24.

Abstract

Residual platelet reactivity (RPR) to adenosine 5' diphosphate (ADP) was an independent predictor of stent thrombosis (ST) in patients receiving drug-eluting stents on dual-antiplatelet treatment and was associated with the cytochrome P450 (CYP)2C19*2 polymorphism. The aim was to evaluate the role of the CYP2C19*2 polymorphism in the occurrence of ST or the composite end point of ST and cardiac mortality within a 6-month follow-up in patients undergoing percutaneous coronary interventions with drug-eluting stent implantation on dual-antiplatelet treatment enrolled in the RECLOSE trial. Seven hundred seventy-two patients were studied for the CYP2C19*2 polymorphism and RPR (using 10-muM ADP-induced platelet aggregation). Patients with ST or the composite of ST and cardiac mortality showed a higher prevalence of carriers of the rare allele (54.1% vs 31.3%; p = 0.025 and 51.7% vs 31.2%; p = 0.020, respectively). At multivariate logistic regression analysis with ST or ST and cardiac mortality as dependent variables and the CYP2C19*2 polymorphism, ADP RPR, and additional previously shown clinical and procedural risk factors for ST as independent variables, the CYP2C19*2 allele (ST odds ratio [OR] 3.43, 95% confidence interval [CI] 1.01 to 12.78, p = 0.047; ST and cardiac mortality OR 2.70, 95% CI 1.00 to 8.42, p = 0.049) and ADP RPR (ST OR 3.08, 95% CI 1.23 to 7.72, p = 0.016; ST and cardiac mortality OR 2.90, 95% CI 1.08 to 12.98, p = 0.019) were independent risk factors. Subjects with the contemporary presence of the CYP2C19*2 allele and ADP RPR showed a strong risk of ST or ST and cardiac mortality (OR 5.79, 95% CI 1.04 to 39.01, p = 0.033 and OR 11.45, 95% CI 1.84 to 71.27, p = 0.009, respectively). In conclusion, the CYP2C19*2 allele was associated with the occurrence of ST or ST and cardiac mortality in high-risk vascular patients on dual-antiplatelet treatment. These findings could impact on the future design of pharmacogenetic antiaggregant strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon, Coronary
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aspirin / administration & dosage
  • Clopidogrel
  • Coronary Thrombosis / etiology
  • Coronary Thrombosis / genetics*
  • Cytochrome P-450 CYP2C19
  • Drug-Eluting Stents / adverse effects*
  • Female
  • Graft Occlusion, Vascular / etiology*
  • Graft Occlusion, Vascular / genetics
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / therapy*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Polymorphism, Genetic
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives

Substances

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