Ticagrelor Aspirin vs Clopidogrel Aspirin inCYP2C19Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile

Abstract

Background and ObjectiveGenotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel aspirin depended onCYP2C19genotype and risk profile. A stratification of patients who carriedCYP2C19loss-of-function (LOF) alleles according to the risk of recurrent stroke may be important for selecting optimal antiplatelet therapy. We aimed to compare the efficacy and safety of ticagrelor aspirin with clopidogrel aspirin inCYP2C19LOF carriers with minor stroke or transient ischemic attack (TIA) stratified by risk profile.MethodsData were obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low-risk and high-risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively).ResultsA total of 6,412CYP2C19LOF carriers were enrolled; ticagrelor aspirin was associated with a reduced risk of primary outcome (new stroke within 90-day follow-up) in patients at low risk (hazard ratio [HR], 0.65; 95% CI, 0.48–0.82), but not in those at high risk (HR, 0.97; 95% CI, 0.73–1.29), compared with clopidogrel aspirin (p= 0.02 for interaction). Secondary outcomes generally went in the same direction as the primary outcome. The primary safety outcome of severe or moderate bleeding did not differ based on risk profile (p= 0.24 for interaction), although the incidence of total bleeding was greater with ticagrelor aspirin than with clopidogrel aspirin among patients at low risk (p< 0.01 for interaction). Analysis in the per-protocol population yielded similar results.DiscussionThis post hoc analysis of CHANCE-2 trial showed thatCYP2C19LOF carriers with minor stroke or TIA at low risk of recurrent stroke received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin.Classification of EvidenceThis study provides Class II evidence thatCYP2C19LOF carriers with minor stroke or TIA at low risk, but not at high risk, of recurrent stroke (by the ESRS) received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin.Trial Registration InformationURL:www.clinicaltrials.gov. Unique identifier:NCT04078737.