Outcomes of Ticagrelor Versus High-dose Clopidogrel in CYP2C19 Intermediate Metabolizer Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes

J Cardiovasc Pharmacol. 2024 Sep 1;84(3):347-355. doi: 10.1097/FJC.0000000000001582.

Abstract

Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) have not come to an agreement. This study aimed to evaluate the clinical benefit of ticagrelor when compared with high-dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention for acute coronary syndromes. Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected through 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, stroke, and stent thrombosis within 12 months. The secondary outcome was Bleeding Academic Research Consortium scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. A total of 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 0.71; 95% confidence interval: 0.32-1.58; adjusted log-rank P = 0.396), but the incidence rate of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events was statistically higher in the loss of function-ticagrelor group than in the loss of function-clopidogrel group (13.53 vs. 6.16 per 100 patient-years; IPTW-adjusted hazard ratio: 2.29; 95% confidence interval: 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.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Acute Coronary Syndrome* / diagnosis
  • Acute Coronary Syndrome* / mortality
  • Acute Coronary Syndrome* / therapy
  • Aged
  • Clopidogrel* / administration & dosage
  • Clopidogrel* / adverse effects
  • Cytochrome P-450 CYP2C19* / genetics
  • Cytochrome P-450 CYP2C19* / metabolism
  • Female
  • Hemorrhage* / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / mortality
  • Pharmacogenomic Variants*
  • Phenotype
  • Platelet Aggregation Inhibitors* / administration & dosage
  • Platelet Aggregation Inhibitors* / adverse effects
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Ticagrelor* / administration & dosage
  • Ticagrelor* / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • Cytochrome P-450 CYP2C19
  • Ticagrelor
  • Clopidogrel
  • CYP2C19 protein, human
  • Platelet Aggregation Inhibitors