A tailored antiplatelet strategy in STEMI patients based on CYP2C19 genotyping is feasible in daily practice-POPular Genetics study

Abstract

Rationale: Treatment with dual antiplatelet therapy (aspirin plus clopidogrel, pra- sugrel or ticagrelor) is essential to prevent atherothrombotic events in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). Although ticagrelor and prasugrel reduce thrombotic events compared to clopidogrel, they increase bleeding risk and costs. Clopidogrel effectiveness varies between patients, partially according to differences in CYP2C19 drug metabolism, but in the subset of CYP2C19 ∗1/∗1 (extensive metabolizer) patients clopidogrel seems equally effective than the newer drugs, with less costs and possibly less bleeding events. The POPular Genetics study tests the hypothesis that CYP2C19 genotype guided antiplatelet is noninferior to the use of ticagrelor or prasugrel, for the combined endpoint of death, myocardial infarction, stroke, stent thrombosis and TIMI major bleeding. However, it is questioned if routine genotyping shortly after pPCI is feasible in daily practice. Methods: All patients randomized to the genotyping arm of the ongoing open label, multicenter POPular Genetics study (NCT01761786) were included in this analysis. For every patient a buccal swab or blood sample was obtained during or shortly after pPCI to perform genotyping, using the SPARTAN RX point-of-care device, a validated in-house TaqMan StepOnePlus assay or shipment to a study site with genotyping equipment. P2Y12 inhibitors were prescribed according to local protocol and subsequently adjusted according to the genotyping results: clopidogrel in CYP2C19 ∗1/∗1 patients and ticagrelor or prasugrel in patients carrying 1 or more ∗2 or ∗3 (loss-of-function) alleles. Results: A total of 669 patients were included in 4 study sites until November 2013. Of those patients, 331 were randomized to the genotyping group, with CYP2C19 ∗1∗/1 in 232 (70.1%), ∗1/∗2 in 91 (27.5%), ∗1/∗3 in 1 (0.3%) and ∗2/∗2 in 7 (2.1%) patients, resp. The time between pPCI and the genotyping result was on average 20:44 hours (range 1:50 -168:49 hours), with 77.4% of results available within 24 hours after pPCI and 92.4% within 48 hours. The P2Y12 inhibitor was switched according to genotyping result in 47.4% of patients, 28x to ticagrelor or prasugrel and 129x to clopidogrel. Conclusion: The ongoing POPular Genetics study shows that it is feasible to tailor antiplatelet treatment in STEMI patients within 24-48hours after pPCI according to CYP2C19 metabolizer status in the vast majority of patients. The efficacy, safety and cost-effectiveness of a tailored antiplatelet strategy are under evaluation.