Key result
Genotype-guided antiplatelet therapy proves feasible in STEMI, delivering ~92% of results within 48 hours.
Why the study?
Although ticagrelor and prasugrel reduce thrombotic events compared to clopidogrel, they increase bleeding risk and costs, and it is uncertain if CYP2C19 genotype-guided antiplatelet therapy is feasible in daily practice after STEMI treated with pPCI.
Is CYP2C19 genotype-guided antiplatelet therapy noninferior to routine ticagrelor or prasugrel for the combined endpoint of death, MI, stroke, stent thrombosis, and major bleeding in STEMI patients undergoing pPCI?
RCT (n=669)
Open-label
randomized
Yes
Is CYP2C19 genotype-guided antiplatelet therapy noninferior to routine ticagrelor or prasugrel for the combined endpoint of death, MI, stroke, stent thrombosis, and major bleeding in STEMI patients undergoing pPCI?
Routine CYP2C19 genotyping to tailor P2Y12 inhibitor therapy in STEMI patients undergoing pPCI is feasible in daily clinical practice, with results available within 24 to 48 hours.
Supports further evaluation of genotype-guided therapy in STEMI; does not yet justify routine clinical use.
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.
No takes yet. Share an insight, caveat, or question.
Bergmeijer et al. (2014) conducted an RCT in ST-segment elevation myocardial infarction (STEMI) (n=669). CYP2C19 genotype-guided antiplatelet strategy vs. Ticagrelor or prasugrel was evaluated on Combined endpoint of death, myocardial infarction, stroke, stent thrombosis and TIMI major bleeding. A CYP2C19 genotype-guided antiplatelet strategy is feasible in STEMI patients undergoing primary PCI, with 92.4% of genotyping results available within 48 hours.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: