The effect of dual antiplatelet therapy in different patterns of watershed infarction: Subgroup analysis of the INSPIRES trial

Watershed infarction (WI) is heterogeneous. This study aims to explore the effect of clopidogrel-aspirin in patients with WI and which WI patterns could gain more benefits. Patients are classified into cortical WI (CWI) (n = 484), internal WI (IWI) (n = 372), CWI+IWI (n = 410), and non-WI (n = 4,033) according to diffusion-weighted magnetic resonance imaging. The results show that patients with WI treated with clopidogrel-aspirin have a lower risk of stroke recurrence compared to aspirin at 90 days (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49-0.93). Specifically, patients receiving clopidogrel-aspirin show a lower rate of recurrent stroke than those receiving aspirin in IWI (HR, 0.54; 95% CI, 0.30-0.97), and with a similar trend in CWI+IWI, but not significant in CWI (p for interaction = 0.41). Clopidogrel-aspirin does not increase moderate-to-severe bleeding across WI patterns. This study reveals that the effect of clopidogrel-aspirin appears consistent across WI subgroups, but it might be more effective in patients with IWI. This study is registered at Clinicaltrials.gov (NCT03635749).