Dual antiplatelet therapy with ticagrelor vs clopidogrel in patients with TIA or minor stroke with or without symptomatic carotid artery stenosis: a post hoc analysis of the CHANCE-2 trial

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.