ADAPT-PCI: CYP2C19 Genotyping Influences Antiplatelet Prescribing Following PCI

Pharmacogenetic testing after a PCI influenced the selection of the antiplatelet drug prescribed, although agreement with genotype-guided recommendations was not universal, according to results of the ADAPT-PCI trial presented by Sony Tuteja, PharmD, MS, on Saturday, March 10, in a Featured Clinical Research session at ACC.18 in Orlando, FL.

Clinical pharmacogenetics guidelines recommend use of prasugrel or ticagrelor among CYP2C19 loss of function (LOF) carriers, because CYP2C19 LOF impairs the effectiveness of clopidogrel after PCI. The primary endpoint of the ADAPT-PCI trial, conducted to provide evidence about the implementation and effectiveness of CYP2C19 testing, was proportion of patients receiving prasugrel or ticagrelor in each arm. The secondary endpoints were agreement with the genotype-guided antiplatelet recommendations.

A total of 504 patients (mean age 63 years; 73 percent men) who were undergoing PCI with stent implantation were randomized to point-of-care CYP2C19 genotyping (n=249) or usual care (n=255). The genotype results and antiplatelet recommendations were provided to the interventional cardiologist, who decided which antiplatelet to prescribe. The mean follow-up was 16.4 months.

In the genotyped group, 28 percent of patients carried CYP2C19 LOF alleles. Prasugrel or ticagrelor was prescribed for significantly more patients in the genotyped group compared with the usual care group (30 vs. 21 percent). Significantly more CYP2C19 LOF carriers versus non-LOF carriers (53 vs. 22 percent) were prescribed prasugrel or ticagrelor. Genotype-guided recommendations were followed in 71 percent of patients. Yet, genotype did not influence prescribing among patients already taking prasugrel or ticagrelor. There were no significant differences between the genotyped and usual care groups for the secondary endpoints of rates of major adverse cardiovascular events (13.7 vs. 10.2 percent) and major bleeding (2.4 vs. 3.1 percent).

While an influence on prescription was seen from the genotyping, the authors concluded that physicians consider both clinical and genetic factors when prescribing antiplatelet agents following PCI. However, the larger question about the use of genotyping to guide antiplatelet selection remains, says Kim A. Eagle, MD, MACC, editor-in-chief of ACC.org. "Will patient outcomes improve because a physician selects an alternative antiplatelet drug because of the genetic testing?"

Keywords: ACC18, ACC Annual Scientific Session, Angiography, Platelet Aggregation Inhibitors, Alleles, Genotype, Incidence, Point-of-Care Systems, Control Groups, Pharmacogenetics, Ticlopidine, Adenosine, Percutaneous Coronary Intervention, Myocardial Infarction, Stroke, Thrombosis, Stents


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