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


OBJECTIVE
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).


CONCLUSIONS
CYP2C19 polymorphism is significantly associated with risk of adverse clinical events in clopidogrel-treated patients.
Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
Liu
L
Mao
Chen
C
Jian
Liu
L
Changzhi
Huang
H
Dan
Huang
H
Suihua
Tang
T
Wenyi
Wu
W
Wei
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006801:Humans; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000295:instrumentation / Q000401:mortality; D010597:Pharmacogenetics; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
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