CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention

Thromb Res. 2016 Nov:147:108-114. doi: 10.1016/j.thromres.2016.10.008. Epub 2016 Oct 7.

Abstract

Introduction: Both CYP2C19 genotyping and platelet function testing are used to predict major adverse cardiac events (MACEs) in Chinese patients treated with clopidogrel and undergoing stent implantation, but the most accurate prognostic technique is still debated. Here, we combine both techniques, to determine if a more accurate prognosis is possible.

Methods: Patients undergoing stent implantation (1104) were genotyped and assessed for platelet reactivity, with a 12-month follow-up. The CYP2C19*2 (rs4244285), and *3 (rs4986893) alleles were genotyped. High on treatment platelet reactivity was defined as adenosine diphosphate (ADP)-induced platelet inhibition ≤30%. MACEs included death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis.

Results and conclusions: Hazard ratios (HRs) for cardiovascular ischemic outcomes based on the two testing methods are as follows. CYP2C19 genotyping: carriers of CYP2C19 loss-of-function alleles, HR: 2.515, 95% confidence interval (CI), 1.150-5.501, P=0.021; ADP-induced platelet inhibition ≤30%, HR: 1.992, 95% CI, 1.040-3.818, P=0.038. An ischemic risk score between zero and two was calculated. Compared with the group with a score of zero, HRs for adverse cardiovascular outcomes were 4.078 for those with a score of two (95% CI: 1.525-10.905, P=0.005). However, there was no significant difference between the group with the score of zero and the group with the score of one. CYP2C19 genotyping combined with platelet reactivity is an independent and additive predictor of 1-year MACE in Chinese patients undergoing stenting with clopidogrel treatment, which is better than either test alone.

Keywords: CYP2C19; Clopidogrel; Genotyping; Platelet function test.

MeSH terms

  • Aged
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • China
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention / adverse effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Prognosis
  • Proportional Hazards Models
  • Stents / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Ticlopidine