Key result
Aspirin-ticagrelor reduces 90-day strokes ~30% versus aspirin-clopidogrel in patients without sCAS.
Why the study?
It was unknown whether the superiority of aspirin-ticagrelor over aspirin-clopidogrel differs between TIA or minor stroke patients with versus without symptomatic carotid artery stenosis.
Does aspirin-ticagrelor reduce new stroke compared to aspirin-clopidogrel in patients with TIA or minor stroke carrying CYP2C19 loss-of-function alleles, depending on the presence of symptomatic carotid artery stenosis?
RCT (n=5,920)
Does aspirin-ticagrelor reduce new stroke compared to aspirin-clopidogrel in patients with TIA or minor stroke carrying CYP2C19 loss-of-function alleles, depending on the presence of symptomatic carotid artery stenosis?
Effect estimate: HR 0.70 (95% CI 0.57 to 0.86)
Absolute Event Rate: 5.52% vs 7.76%
p-value: p=0.0006
Genotype-guided dual antiplatelet therapy with aspirin-ticagrelor reduces recurrent stroke in patients with TIA or minor stroke without symptomatic carotid artery stenosis, but its benefit in those with sCAS is unclear.
Background and purpose Symptomatic internal carotid artery stenosis (sCAS) is an essential cause of transient ischaemic attack (TIA) or minor stroke. We aimed to evaluate whether the superiority of aspirin-ticagrelor over aspirin-clopidogrel varies between patients with sCAS or not. Methods This was a post-hoc analysis of the High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II (CHANCE-2) trial, all of which were CYP2C19 loss-of-function alleles carriers. The primary exposures of interest were the treatment group and sCAS status. The primary efficacy endpoint was the new stroke assessed within 90 days. Results A total of 5920 (92.3%) from 6412 were analysed, including 197 (3.3%) with sCAS and 5723 (96.7%) without sCAS. Stroke recurrence occurred in 13 (12.15%) and 11 (12.22%) patients with sCAS who received aspirin-ticagrelor and aspirin-clopidogrel, respectively (adjusted HR, 1.04; 95% CI, 0.46 to 2.36; p=0.930). Among patients without sCAS, there were 158 cases (5.52%) of new strokes in the aspirin-ticagrelor group and 222 cases (7.76%) in the aspirin-clopidogrel group (HR, 0.70; 95% CI, 0.57 to 0.86; p=0.0006). The treatment-by-sCAS subtype was not significant (p=0.405). Conclusions Genotype-guided dual antiplatelet treatment with aspirin-ticagrelor may be beneficial for preventing recurrent strokes in patients without sCAS; however, it appears less effective in those with sCAS. No significant interaction was found between the treatment and sCAS subtypes. Trial registration number NCT04078737 .
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Xie et al. (2025) conducted an RCT in TIA or minor stroke (n=5,920). aspirin-ticagrelor vs. aspirin-clopidogrel was evaluated on new stroke assessed within 90 days (HR 0.70, 95% CI 0.57 to 0.86, p=0.0006). Aspirin-ticagrelor reduced new strokes at 90 days vs aspirin-clopidogrel in patients without sCAS (HR 0.70; 95% CI 0.57-0.86; p=0.0006), but not in those with sCAS (interaction p=0.405).
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