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Ticagrelor-Aspirin vs Clopidogrel-Aspirin in CYP2C19 Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile

First author：Anxin Wang,Xia Meng

Corresponding author：Yongjun Wang

CHANCE-2 Clopidogrel Essen Stroke Risk Score Stroke Ticagrelor

essential_information

2022-12-19

Published articles

Journal：Neurology

Publication type: Original Article

IF(IF): 11.8

PMID: 36535779 Link To Pubmed Full text Download

Background And Purpose

Genotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel-aspirin depended on CYP2C19 genotype and risk profile. A stratification of patients who carried CYP2C19 loss of function (LOF) alleles according to risk of recurrent stroke may be important for selecting optimal antiplatelet therapy. We aimed to compare the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in CYP2C19 LOF carriers with minor stroke or transient ischemic attack (TIA) stratified by risk profile.

Method

Data were obtained from Ticagrelor or Clopidogrel with Aspirin in High Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low and high risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively).

Conclusion

This study provides Class II evidence that CYP2C19 LOF carriers with minor stroke or TIA at low risk, but not at high risk, of recurrent stroke (by ESRS score) received a greater benefit from ticagrelor-aspirin than clopidogrel-aspirin.

Main results

A total of 6,412 CYP2C19 LOF 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% confidence interval [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), though the incidence of total bleeding was greater with ticagrelor-aspirin than clopidogrel-aspirin among patients at low risk (P<0.01 for interaction). Analysis in the per-protocol population yielded similar results.