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CYP2C19 allele linked with increased risk for major adverse CV events in patients given clopidogrel for PCI
Mega J. JAMA. 2010;304:1821-1830.
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Results from new meta-analysis published in the Journal of the American Medical Association suggested an association between the CYP2C19 allele and a significantly elevated risk for major adverse CV events, including CV death and MI, in patients given clopidogrel for percutaneous coronary intervention.
“By performing a collaborative meta-analysis with data by genotype, we found that among patients treated with clopidogrel predominantly for PCI, carriage of even one reduced-function CYP2C19 allele is associated with an increased risk of adverse CV events, particularly stent thrombosis,” the researchers wrote.
The study began as a literature search in Medline, Cochrane and Embase databases for genetic studies in which clopidogrel was initiated. The final analysis population included 9,685 patients, 91.3% of whom underwent PCI and 54.5% had acute coronary syndromes. The composite endpoint was determined as CV death, MI or stroke.
Overall, 863 patients experienced the composite endpoint, and in the patients evaluated for stent thrombosis (n=5,894), it was reported in 1.4% (n=84).
For the 26.3% of patients with one reduced function CYP2C19 allele, there was an increased risk of the composite endpoint (HR=1.55; 95% CI, 1.11-2.17) vs. noncarriers. The risk was slightly more pronounced for the 2.2% of patients with two reduced-function CYP2C19 alleles (HR=1.76; 95% CI, 1.24-2.50) when compared with noncarriers. The risk for stent thrombosis was also higher for both carriers of one (HR=2.67; 95% CI, 1.69-4.22) and two (HR=3.97; 95% CI, 1.75-9.02) CYP2C19 reduced-function alleles vs. noncarriers.
“The findings of this collaborative meta-analysis demonstrate that common genetic variants in the CYP2C19 gene are associated with almost one in three patients not receiving ideal protection from ischemic events when treated with standard doses of clopidogrel for PCI,” the researchers noted in their concluding remarks. “Given how widely clopidogrel is used to treat patients with CVD, determination of the optimal antiplatelet treatment doses or regimens for individual patients is needed to tailor therapy appropriately.”
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