Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype

Background: Guidelines favor ticagrelor or prasugrel over clopidogrel in patients with myocardial infarction. However, the POPular Genetics trial (Patient Outcome After Primary Percutaneous Coronary Intervention [PCI]) showed that in patients with primary PCI, a CYP2C19 genotype–guided strategy was associated with a lower bleeding risk without increasing thrombotic risk, compared with routine ticagrelor/prasugrel treatment. Nevertheless, optimal P2Y 12 inhibitor treatment in specific CYP2C19 genetic subgroups is still a subject of debate. Methods: A prespecified subanalysis of the POPular Genetics trial was performed, using patients in whom CYP2C19 *2, *3, and *17 genotypes was determined. Two different analyses were planned. The first assessed the effect of the CYP2C19 *17 allele in clopidogrel-treated patients. The second compared the effect of clopidogrel in noncarriers of a loss-of-function allele with ticagrelor/prasugrel–treated patients, irrespective of CYP2C19 genotype. Main outcomes were a thrombotic outcome (cardiovascular death, myocardial infarction, stent thrombosis, and stroke) and a bleeding outcome (PLATO [Platelet Inhibition and Patient Outcomes] major and minor bleeding) after 12 months. Results: A total of 2429 patients were used for analyses. In the first analysis, the CYP2C19 *17 polymorphism was not found to have a significant influence on thrombotic (adjusted hazard ratio, 0.95 [95% CI, 0.45–2.02]) or bleeding outcomes (adjusted hazard ratio, 0.74 [95% CI, 0.48–1.18]). In the second analysis, clopidogrel was associated with a lower number of bleeding events compared with ticagrelor/prasugrel (9.9% versus 11.7%, adjusted hazard ratio, 0.74 [95% CI, 0.56–0.96]), without a significant increase in thrombotic events (3.4% versus 2.5%, adjusted hazard ratio, 1.14 [95% CI, 0.68–1.90]). Conclusions: In patients with primary PCI not carrying a CYP2C19 loss-of-function allele, the use of clopidogrel compared with ticagrelor or prasugrel was associated with lower bleeding rates, without an increase in thrombotic events. No effect on clinical outcomes was found for the CYP2C19 *17 polymorphism. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01761786. URL: https://www.trialregister.nl/ ; Unique identifier: NL2872.

Abstract 16390: Cost-effectiveness of a CYP2C19 Genotype-guided Antiplatelet Strategy in ST-elevation Myocardial Infarction Patients

Introduction: The POPular Genetics trial demonstrated that a genotype-guided strategy to select antiplatelet therapy in patients with ST-elevation myocardial infarction (STEMI) compared to universal treatment with ticagrelor or prasugrel, resulted in a reduction in bleedings without an increase in the thrombotic risk. The objective of this analysis was to assess the cost-effectiveness of the genotype-guided strategy. Methods: In the POPular Genetics trial, STEMI patients who underwent primary percutaneous coronary intervention were randomized to an intervention or a control arm. In the intervention arm CYP2C19 genetic testing for the *2 and *3 loss-of-function alleles took place. Carriers of a loss-of-function allele were treated with ticagrelor or prasugrel, while noncarriers were treated with clopidogrel. In the control arm patients were treated with ticagrelor or prasugrel. An alongside clinical-trial cost-effectiveness analysis was conducted based on a decision-model with 1000 patients in both groups. A hybrid model, consisting of a 1-year decision tree combined with a 25-years Markov model was developed, to estimate the life-time cost-effectiveness from a societal perspective. Outcome measures were costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to account for the uncertainty around the key parameters. In an exploratory analysis the price for ticagrelor and prasugrel was the same as clopidogrel, to simulate the effect of generic ticagrelor and prasugrel in the future. Results: The genotype-guided strategy resulted in 26.87 QALY gained with cost-savings of є601,807 indicating that the genotype-guided strategy is a cost-saving intervention. The exploratory analysis - keeping the price of antithrombotic therapies at the same price level - resulted in cost-savings of є137,980. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the base-case analysis. Conclusion: Based on the POPular Genetics trial, a genotype-guided strategy compared to universal ticagrelor or prasugrel treatment resulted in favorable cost-effectiveness with QALYs gained and cost-savings.