Early CYP2C19 genetic testing to guide the selection of oral P2Y12 inhibitor therapy in patients undergoing PCI was noninferior to standard treatment with ticagrelor or prasugrel at 12 months in terms of thrombotic events, based on findings from the POPular Genetics trial presented Sept. 3 during ESC Congress 2019 and published in the New England Journal of Medicine. Daniel M.F. Claassens, MD, and colleagues also noted that the CYP2C19 genotype-guided approach resulted in a lower incidence of bleeding.

The study randomized 2,488 patients undergoing primary PCI with stent implantation to either a genotype-guided approach (n=1,242) or standard treatment (n=1,246) for 12 months. The two primary outcomes were net adverse clinical events (i.e, death from any cause, myocardial infarction, definite stent thrombosis, stroke or major bleeding) at 12 months and major or minor bleeding at 12 months. Patients carrying the CYP2C19*2 or CYP2C19*3 loss-of-function alleles in the genotype-guided group received ticagrelor or prasugrel, and noncarriers received clopidogrel.

In overall results, the primary combined outcome occurred in 63 patients (5.1 percent) in the genotype-guided group compared with 73 patients (5.9 percent) in the standard-treatment group. In the genotype-guided group, the primary bleeding outcome occurred in 122 patients (9.8 percent) compared with 156 patients (12.5 percent) in the standard-treatment group.

Researchers noted there was no difference in major bleeding between both groups (2.3 percent in both); however, the between-group difference in the primary bleeding outcome was largely driven by a lower incidence of minor bleeding in the genotype-guided group.

Claassens, et al., highlighted "lower-than-anticipated incidence of the primary combined outcome, and the fact that genetic variation is not the only factor contributing to high platelet reactivity" among the trial's limitations. The also cautioned that a "strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients" given there are additional polymorphisms of the CYP2C19 gene for which data are conflicting.

Keywords: ESC 19, ESC Congress, Percutaneous Coronary Intervention, Angiography

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