Neurotherapeutics. 2026 Jul 10;23(4):e00963. doi: 10.1016/j.neurot.2026.e00963. Online ahead of print.
ABSTRACT
Patients with established cardiovascular disease (CVD) may have a higher risk of recurrent stroke and a higher prevalence of antiplatelet resistance than those without CVD. This study investigated the efficacy and safety of dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin in patients with established CVD. This is a secondary post hoc analysis of the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Patients with mild ischemic stroke (IS) or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause were randomized to receive either DAPT or aspirin alone within 72 h after symptom onset. Established CVD was defined as a prior diagnosis of IS, coronary artery disease, TIA, or peripheral arterial disease. The primary efficacy and safety outcomes were the occurrence of new stroke and moderate-to-severe bleeding within 90 days. This study included 6100 patients, with a mean age of 63.7 ± 9.6 years and 35.8% of female. DAPT was associated with a reduced risk of new stroke (hazard ratio [HR] = 0.67, 95%CI: 0.54-0.85, P < 0.001) in non-CVD patients but not in those with established CVD (HR = 0.97, 95%CI: 0.73-1.28, P = 0.82), compared with aspirin (P for interaction = 0.04). Moderate-to-severe bleeding did not differ by antiplatelet treatments across CVD subgroups (P for interaction = 0.32). In the INSPIRES trial, patients with established CVD may benefit less from clopidogrel-aspirin in reducing the risk of recurrent stroke within 90 days than those without CVD after mild IS or high-risk TIA. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635749.
PMID:42430849 | DOI:10.1016/j.neurot.2026.e00963