Antiplatelet effect of ticagrelor with aspirin in acute minor stroke and transient ischemic attack stratified by CYP2C19 metabolizer status: subgroup analysis of the PRINCE trial

Aging (Albany NY). 2020 Dec 19;13(3):3994-4006. doi: 10.18632/aging.202366. Epub 2020 Dec 19.

Abstract

Studies on antiplatelet effect of ticagrelor/aspirin and clopidogrel/aspirin in patients with acute minor stroke and transient ischemic attack (TIA) stratified by CYP2C19 metabolizer status is limited. We gained data from the Platelet Reactivity In Non-disabling Cerebrovascular Events study. Platelet reactivity was tested at baseline, 2 hours, 24 hours, 7 days and 90 days after initial dose, including high on-treatment platelet reactivity (HOPR), which was defined as P2Y12 reaction unit >208, and percentage inhibition of platelet aggregation (IPA). A total of 365 patients were included. There were 199 (54.5%) individuals classified as carriers of CYP2C19 loss-of-function alleles. For carriers and non-carriers, the proportions of HOPR were significantly lower in those with ticagrelor/aspirin compared with those with clopidogrel/aspirin at 2 hours, 24 hours, 7 days, respectively (all p<0.05). IPA was higher at all time points except at baseline in patients with ticagrelor/aspirin compared with those with clopidogrel/aspirin in both carriers and non-carriers of CYP2C19 lose-of-function alleles (all p<0.05). Our findings showed that ticagrelor/aspirin therapy possessed greater platelet inhibition and more rapid onset in platelet inhibition compared with clopidogrel/aspirin therapy both in carriers and non-carriers of CYP2C19 lose-of-function alleles with acute minor stroke or TIA.

Keywords: antiplatelet; clopidogrel; high platelet reactivity; inhibition of platelet aggregation; ticagrelor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin* / pharmacology
  • Aspirin* / therapeutic use
  • Blood Platelets / drug effects
  • Clopidogrel / pharmacology
  • Clopidogrel / therapeutic use
  • Cytochrome P-450 CYP2C19 / genetics*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ischemic Attack, Transient / drug therapy
  • Ischemic Attack, Transient / epidemiology
  • Ischemic Attack, Transient / genetics
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors* / pharmacology
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Polymorphism, Single Nucleotide / genetics
  • Randomized Controlled Trials as Topic
  • Stroke* / drug therapy
  • Stroke* / epidemiology
  • Stroke* / genetics
  • Ticagrelor* / pharmacology
  • Ticagrelor* / therapeutic use

Substances

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