Ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA stratified by age and renal function: CHANCE-2 trial substudy.

Objective: To compare the efficacy and safety of ticagrelor versus clopidogrel in stroke patients who were CYP2C19 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).

Results: In patients with eGFR >90 mL/min/1.73 m², ticagrelor-aspirin was associated with a significantly lower risk of the subsequent stroke within 90 days compared with the clopidogrel-aspirin in those aged over 65 years (HR 0.53, 95% CI 0.33-0.85, p = 0.008) and under 65 years (HR, 0.67, 95% CI, 0.47-0.96, p = 0.03). While in those with eGFR 60-89 mL/min/1.73 m², ticagrelor did not show superiority over clopidogrel in reducing stroke regardless of age category (age ≥ 65: HR 1.14, 95% CI 0.71-1.84, p = 0.59; age < 65: HR 0.40, 95% CI 0.12-1.33, p = 0.13). The incidence of mild bleeding events was higher with ticagrelor-aspirin treatment in those aged < 65 years with eGFR ≥90 mL/min/1.73 m² (HR 3.33, 95% CI 2.18-5.10, p < 0.001) and in those aged ≥ 65 years with eGFR <60mL/min/1.73 m² (HR 8.68, 95% CI 1.06-71.1, p = 0.04).

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.