Efficacy and Safety of Dual Antiplatelet Treatment up to 72 Hours in Acute Ischemic Stroke Stratified by Glycemic Status.

Abstract

The objective was to investigate the efficacy and safety of clopidogrel-aspirin versus aspirin alone in patients after ischemic stroke by glycemic status using data from the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) were randomized to clopidogrel-aspirin or aspirin alone. They were categorized into 3 subgroups according to glycemic status based on medical history and diagnosis by a clinician during hospitalization: without type 2 diabetes mellitus, with newly diagnosed type 2 diabetes, and with a history of type 2 diabetes mellitus. The primary efficacy and safety outcomes were new stroke and moderate-to-severe bleeding risk within 90-day follow-up. A total of 6,100 patients were enrolled (3,050 in each arm), with a median age of 65 years (interquartile range [IQR], 57-71) and 2,185 female (35.8%). Clopidogrel-aspirin treatment was associated with a reduction in recurrent stroke compared with aspirin alone in patients without type 2 diabetes mellitus (6.3% vs 8.4%; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59-0.94; p = 0.01) and those with newly diagnosed type 2 diabetes mellitus (5.8% vs 13.0%; HR, 0.30; 95% CI, 0.14-0.66; p = 0.002), but not in those with a history of type 2 diabetes mellitus (10.0% vs 9.9%; HR, 0.98; 95% CI, 0.72-1.33; p = 0.88) (p for interaction = 0.03). Moderate-to-severe bleeding events did not differ significantly by treatment across glycemic subgroups. In the INSPIRES trial, patients without or with type 2 diabetes mellitus derived greater benefit from clopidogrel-aspirin than those with a history of type 2 diabetes mellitus after mild ischemic stroke or high-risk TIA. INSPIRES, NCT03635749. Registered 15 August 2018, https://clinicaltrials.gov/search?cond=NCT03635749. ANN NEUROL 2025;98:174-182.