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Patients who had CYP2C19*2 genetic variant in the CYP2C19 gene and were treated with clopidogrel after a myocardial infarction (MI) demonstrated worse cardiovascular outcomes than patients with a normal copy of the cytochrome P450 2C19 encoding gene, according to a study published in the Lancet. The study population was composed of 259 patients, all under the age of 45, who received clopidogrel treatments for at least one month (median exposure time was 1.07 years (IQR 0.28-3.0)). Patients who were carriers of the CYP2C19*2 genetic variant had 15 primary endpoint events, which was a composite of death, MI, and urgent revascularisation during treatment with clopidogrel, while non-carriers had only 11 primary endpoint events (HR 3.69 (95% CI 1.69-8.05), p=0.0005). Further, the study demonstrated that the CYP2C19*2 genetic variant "was the only independent predictor of cardiovascular events (HR 4.04 (1.81-9.02), p=0.0006)." The investigators noted that additional genetic variants, such as CYP2C19*17, may play a role in the reduced responsiveness to clopidogrel and that it remains unclear if a higher maintenance dose could overcome this reduced clopidogrel responsiveness.(Lancet by Jean-Philippe Collet, et al.)
