Effect of history of hypertension on efficacy of clopidogrel-aspirin in ischemic stroke

Background: Patients with different hypertension status could potentially respond differently to the treatment of clopidogrel-aspirin owing to thrombosis, antiplatelet resistance, and platelet reactivity. Aims: The aim of the study is to examine the efficacy and safety of clopidogrel-aspirin in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) according to different hypertension status. Methods: In the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, patients were randomized to either clopidogrel-aspirin or aspirin group. The primary outcome was any new ischemic or hemorrhagic stroke within 90 days. Hypertension status was classified into two categories based on medical history: patients with or without hypertension. Results: Among 6100 patients with complete data of hypertension status, 3915 (64.2%) were men. Clopidogrel-aspirin compared with aspirin was associated with reduced incidence of new stroke in patients without hypertension (hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.44−0.86, p = 0.004), but not in patients with hypertension (HR: 0.87, 95% CI: 0.71−1.07, p = 0.18; p = 0.085 for interaction). Conclusions: In this study, patients without hypertension may have more benefit from receiving treatment with clopidogrel-aspirin than those with hypertension. This finding can be used as an enrichment strategy in the future secondary stroke prevention randomized clinical trials of dual antiplatelet therapy. Trial Registration: The INSPIRES trial was registered at http://www.clinicaltrials.gov (unique identifier: NCT03635749).