Clopidogrel versus Ticagrelor in CYP2C19 Loss-of-Function Allele Noncarriers: A Real-World Study in China

Thromb Haemost. 2022 May;122(5):842-852. doi: 10.1055/s-0041-1735193. Epub 2021 Aug 24.

Abstract

Objective: This article compares the clinical outcomes of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) without cytochrome P450 (CYP)2C19 loss-of-function (LOF) alleles and investigates whether clopidogrel could be an alternative P2Y12 inhibitor without increasing the risk of ischemic events.

Methods: Patients were divided into the clopidogrel-treated group and the ticagrelor-treated group. Inverse probability of treatment weighting (IPTW) calculated by propensity scores was used to adjust confounding covariates. The primary outcome was major adverse cardiovascular or cerebrovascular events (MACCEs) within 12 months. The secondary outcomes were MACCEs plus unstable angina, and clinically significant bleeding events.

Results: Finally, 2,199 patients were included. Of them, 1,606 were treated with clopidogrel, and 593 were treated with ticagrelor. The mean age of the original cohort was 59.92 ± 9.81 years. During the 12-month follow-up period, MACCEs occurred in 89 patients (4.0%). No significant differences were observed in MACCEs (IPTW-adjusted hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.65-1.18), MACCEs plus unstable angina (IPTW-adjusted HR, 1.20; 95% CI, 0.91-1.59), or clinically significant bleeding events (IPTW-adjusted HR, 0.81; 95% CI, 0.53-1.23) between the clopidogrel- and ticagrelor-treated groups.

Conclusion: In patients with ACS without CYP2C19 LOF alleles, clopidogrel was not associated with a higher risk of MACCEs when compared with ticagrelor. The main findings of this study support use of clopidogrel in CYP2C19 LOF noncarriers as an alternative P2Y12 inhibitor, which may reduce medical expenses and adverse reactions caused by more potent P2Y12 inhibitors in these patients.

MeSH terms

  • Acute Coronary Syndrome* / drug therapy
  • Acute Coronary Syndrome* / genetics
  • Aged
  • Alleles
  • Angina, Unstable / drug therapy
  • Clopidogrel / adverse effects
  • Cytochrome P-450 CYP2C19 / genetics
  • Hemorrhage / chemically induced
  • Humans
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Ticagrelor / adverse effects
  • Treatment Outcome

Substances

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