Key result
Ticagrelor-aspirin cuts recurrent stroke ~47% vs clopidogrel-aspirin in older CYP2C19 loss-of-function carriers with normal eGFR.
Why the study?
To evaluate the efficacy and safety of ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA stratified by age and renal function.
Does ticagrelor-aspirin reduce the occurrence of a new stroke compared to clopidogrel-aspirin in CYP2C19 loss-of-function carriers with stroke or TIA?
RCT (n=6,378)
Double-blind
1:1
Yes
Does ticagrelor-aspirin reduce the occurrence of a new stroke compared to clopidogrel-aspirin in CYP2C19 loss-of-function carriers with stroke or TIA?
In CYP2C19 loss-of-function carriers with stroke or TIA, ticagrelor-aspirin appears to benefit elderly patients with normal renal function compared to clopidogrel-aspirin.
Supports ticagrelor-aspirin over clopidogrel-aspirin in elderly CYP2C19 LOF carriers with normal renal function; extends genotype-guided DAPT evidence to this subgroup.
OBJECTIVE: loss-of-function (LOF) carriers stratified by age and renal function. METHODS: Patients in the CHANCE-2 trial were randomized to ticagrelor-aspirin or clopidogrel-aspirin treatment. The primary efficacy outcome was occurrence of a new stroke within 90 days, while bleeding was assessed for safety. Patients were categorized based on age and estimated glomerular filtration rate (eGFR). CONCLUSIONS: Elderly patients with normal renal function appear to benefit from ticagrelor compared with clopidogrel. Both younger patients with normal renal function and those with advanced age and renal insufficiency are prone to mild bleeding.
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Wu et al. (2025) conducted an RCT in Minor ischemic stroke or high-risk TIA with CYP2C19 loss-of-function allele (n=6,378). Ticagrelor-aspirin vs. Clopidogrel-aspirin was evaluated on New stroke within 90 days (subgroup: age ≥65 years, eGFR ≥90 ml/min/1.73 m2) (HR 0.53, 95% CI 0.33-0.85, p=0.008). Ticagrelor-aspirin reduced the risk of recurrent stroke within 90 days by 47% compared to clopidogrel-aspirin in CYP2C19 loss-of-function carriers aged over 65 years with normal renal function (HR 0.53).
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