MedWire News: Patients receiving clopidogrel after myocardial infarction (MI) who carry a variant form of a clopidogrel-metabolizing gene have a poorer short-term outcome than noncarriers, reveals research published in the New England Journal of Medicine.
The study is accompanied by a second article, also reported by MedWire News, demonstrating an increased risk for adverse events in acute coronary syndromes patients with the same cytochrome P-45 enzyme CYP2C19 allele.
“Among patients with an acute MI who were receiving clopidogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate for subsequent cardiovascular events than those who were not,” report Tabassome Simon (Université Pierre et Marie Curie (UPMC) Paris, France) and co-workers.
“This effect was particularly marked among the patients undergoing percutaneous coronary intervention (PCI).”
The team genotyped 2208 acute MI patients receiving clopidogrel for genes modulating clopidogrel absorption (multi-drug resistance-1 [ABCB1]), metabolic activation (CYP3A5 and CYP2C19), and biologic activity (P2RY12 and ITGB3).
During 1 year of follow-up, 225 patients died, and 94 patients experienced nonfatal stroke or MI.
Analysis showed that single nucleotide polymorphisms in the CYP3A5, P2RY12 and ITGB3 genes had no impact on patient outcome. In contrast, patients carrying two copies of the ABCB variant TT allele were significantly more likely to experience an adverse outcome than those with the wild-type CC allele (15.5% vs 10.7%, adjusted hazard ratio [HR]=1.72).
Furthermore, patients carrying two of three different possible loss-of-function alleles for the CYP2C19 gene were significantly more likely to have an adverse event than patients without the variant forms (21.5% vs 13.3%, HR=1.98).
Patients who underwent PCI while hospitalized for MI were particularly at risk for adverse events if they carried two CYP2C19 loss-of-function alleles, with a HR of 3.58 versus noncarriers, say Simon et al.
Noting that clopidgorel therapy is routinely recommended for about a year after MI, especially in patients undergoing PCI, the researchers suggest: “Among patients for whom clopidogrel therapy is indicated, genotyping rather than repeated platelet monitoring could be an affordable and suitable strategy to identify patients at high risk for atherothrombotic events.”
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