Clopidogrel-aspirin reduced recurrent stroke vs aspirin in patients without diabetes (HR 0.75) and newly diagnosed diabetes (HR 0.30), but not with prior diabetes (HR 0.98; P for interaction=0.03).
RCT (n=6,100)
Does clopidogrel-aspirin reduce new stroke compared to aspirin alone in patients with mild ischemic stroke or high-risk TIA across different glycemic statuses?
Clopidogrel-aspirin reduces recurrent stroke risk compared to aspirin alone in patients with mild ischemic stroke or high-risk TIA who do not have a history of type 2 diabetes, but lacks benefit in those with established diabetes.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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. TRIAL REGISTRATION: INSPIRES, NCT03635749. Registered 15 August 2018, https://clinicaltrials.gov/search?cond=NCT03635749. ANN NEUROL 2025;98:174-182.
Zhou et al. (Tue,) conducted a rct in mild ischemic stroke or high-risk transient ischemic attack (TIA) (n=6,100). clopidogrel-aspirin vs. aspirin alone was evaluated on new stroke and moderate-to-severe bleeding risk within 90-day follow-up. Clopidogrel-aspirin reduced recurrent stroke vs aspirin in patients without diabetes (HR 0.75) and newly diagnosed diabetes (HR 0.30), but not with prior diabetes (HR 0.98; P for interaction=0.03).