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Genetic testing non-inferior to standard drug treatment with regard to thrombotic events

ESC 2019
Early CYP2C19 genetic testing to guide the selection of oral P2Y12 inhibitor therapy in patients undergoing percutaneous coronary intervention (PCI) has been shown to be non-inferior to standard treatment with ticagrelor or prasugrel at 12 months regarding thrombotic events. Importantly, the CYP2C19 genotype-guided approach also resulted in a lower incidence of bleeding.

Claassens and colleagued enrolled 2,488 patients who underwent primary PCI with stent implantation, who were randomised to either a genotype-guided approach (n=1,242) or standard treatment (n=1,246) for the duration of 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 who were carriers of the CYP2C192 or CYP2C193 loss-of-function alleles in the genotype-guided group received ticagrelor or prasugrel, whilst non-carriers were treated with clopidogrel. It was found that the primary combined outcome occurred in 5.1% of patients in the genotype-guided group compared with 5.9% of patients in the standard-treatment group. In the genotype-guided group, the primary bleeding outcome occurred in 9.8% of patients vs 12.5% of patients in the standard-treatment group. No difference was observed with regard to major bleeding; this was 2.3% for both groups. The authors indicated that the incidence of the primary combined outcome was lower than what was expected. Similarly, they pointed out that genetic variation is not the only factor which contributes to high platelet reactivity. So, despite these findings, a strategy which is exclusively based on the CYP2C19 genotype may not be the best strategy for particular patients due to the fact that additional un-investigated polymorphisms of the CYP2C19 gene exist without known clinical consequences [1].

1. Claassens D. POPular Genetics - Genotype-guided oral P2Y12-inhibition in patients with ST-segment elevation myocardial infarction undergoing primary PCI: a randomized, open-label, multicenter trial. FP Number 6047. . ESC Congress 2019, 31 Aug-4 Sept, Paris, France.

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