Cytochrome CYP2C19 polymorphism and risk of adverse clinical events in clopidogrel-treated patients: a meta-analysis based on 23,035 subjects

Arch Cardiovasc Dis. 2013 Oct;106(10):517-27. doi: 10.1016/j.acvd.2013.06.055. Epub 2013 Sep 27.

Abstract

Background: Previous studies have investigated the relationship between CYP2C19 polymorphism and clinical prognosis in coronary artery disease patients treated with clopidogrel, but the results were inconsistent.

Aims: To assess the impact of CYP2C19 polymorphism on the risk of adverse clinical events by performing a meta-analysis of relevant studies in the last few years.

Methods: Prospective cohort studies or post-hoc analyses of randomized controlled trials were identified from the databases of PubMed/Medline, EMBASE and the Cochrane Library. Endpoints were fatal or non-fatal myocardial infarction, cardiovascular or all-cause death, definite or probable stent thrombosis, target vessel revascularization, target lesion revascularization, urgent revascularization, ischaemic stroke and bleeding. Pooled effects were measured by odds ratios (ORs) with 95% confidence intervals (CIs).

Results: A total of 21 studies involving 23,035 patients were included. Compared with non-carriers of the CYP2C19 variant allele, the carriers were found to have an increased risk of adverse clinical events (OR 1.50, 95% CI 1.21-1.87; P=0.0003), myocardial infarction (OR 1.62, 95% CI 1.35-1.95; P<0.00001), stent thrombosis (OR 2.08, 95% CI 1.67-2.60; P<0.00001), ischaemic stroke (OR 2.14, 95% CI 1.36-3.38; P=0.001) and repeat revascularization (OR 1.35, 95% CI 1.10-1.66; P=0.004), but not of mortality (P=0.500) and bleeding events (P=0.930).

Conclusion: CYP2C19 polymorphism is significantly associated with risk of adverse clinical events in clopidogrel-treated patients.

Keywords: ACS; Acute coronary syndrome; CAD; CI; CYP; CYP2C19; Clopidogrel; Confidence interval; Coronary artery disease; Cytochrome P450; MI; Maladie coronaire; Meta-analysis; Myocardial infarction; Méta-analyse; OR; Odds ratio; PCI; PCR; Percutaneous coronary intervention; Polymerase chain reaction; ST; Stent thrombosis; TLR; TVR; Target lesion revascularization; Target vessel revascularization.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Chi-Square Distribution
  • Clopidogrel
  • Coronary Thrombosis / enzymology
  • Coronary Thrombosis / genetics
  • Coronary Thrombosis / mortality
  • Cytochrome P-450 CYP2C19
  • Drug Resistance / genetics
  • Genotype
  • Humans
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / genetics
  • Odds Ratio
  • Percutaneous Coronary Intervention / adverse effects*
  • Percutaneous Coronary Intervention / instrumentation
  • Percutaneous Coronary Intervention / mortality
  • Pharmacogenetics
  • Phenotype
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Risk Factors
  • Stents
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / metabolism
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

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