Outcomes of ticagrelor versus high dose clopidogrel in CYP2C19 intermediate metabolizer undergoing percutaneous coronary intervention for acute coronary syndromes

Abstract

Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) has not come to an agreement. The current study was to evaluate the clinical benefit of ticagrelor when compared with high dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected via electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction (MI), stroke, stent thrombosis within 12 month. The secondary outcome was Bleeding Academic Research Consortium (BARC) scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs 9.52 per 100 patient-years; IPTW-adjusted hazard ratio (HR) 0.71; 95% confidence interval (CI): 0.32-1.58; adjusted log-rank P=0.396), but the incidence rate of BARC type 2, 3 or 5 bleeding events was statistically higher in LOF-ticagrelor group than LOF-clopidogrel group (13.53 vs 6.16 per 100 patient-years; IPTW-adjusted HR: 2.29; 95% CI: 1.10-4.78; adjusted log-rank P=0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.