GIANT: CYP2C19 Genetic Profiling for Thienopyridine Management Post-PCI in AMI

CYP2C19 genetic profiling of patients for thienopyridine management following primary percutaneous coronary intervention (PCI) may help cardiology teams adjust treatment and improve ischemic outcomes, according to results from the GIANT Trial released at TCT 2013.

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Trial investigators performed genetic profiling on 1,499 patients within 48 hours after primary PCI to detect a loss of CYP2C19 gene function and identify a resistance to clopidogrel. A total of 22 percent of patients (n=319) had a profile associated with a CYP2C19 loss of function and were classified as slow responders. The remaining patients constituted the control group.

Dual-antiplatelet therapy was prescribed for 12 months after PCI and one year follow up was performed in 96.4 percent of patients (n=1,445) including objective assessment of compliance. In the slow responder group, 85 percent received an adjusted thienopyridine regimen after the release of the genetic profile. Within the slow responder group, the patients that received adjusted therapy experienced fewer adverse events after one year compared to those that did not (3.3 percent vs. 15.6 percent, respectively). The study investigators also noted that patients receiving adjusted therapy experienced a similar rate of adverse events as the control group (3.3 percent vs. 3.04 percent).

According to lead investigator Bernard R. Chevalier, MD, from L'Institut CardioVasculaire Paris-Sud in Massy, France, poor compliance to treatment was objectively identified in 4.9 percent of patients at one year, and those patients experienced numerically more ischemic events. He also noted that study results did not indicate a "higher risk of major bleeding, even in the case of patients with a gain-of-function allele genotype."

Moving forward, Chevalier suggests the study findings may be useful in helping to determine alternative treatment strategies for patients with limited CYP2C19 gene function.

Keywords: France, Follow-Up Studies, Pyridines, Ticlopidine, Genotype, Hemorrhage, Percutaneous Coronary Intervention

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