Key result
Metabolic syndrome is linked to ~39% higher 90-day recurrent stroke risk without altering clopidogrel-aspirin efficacy.
Why the study?
Metabolic syndrome attenuates antiplatelet agent effects, leaving the efficacy and safety of clopidogrel–aspirin therapy for secondary stroke prevention in patients with metabolic syndrome unclear.
Does clopidogrel-aspirin therapy reduce new stroke compared to aspirin alone in patients with mild ischemic stroke or high-risk transient ischemic attack, and is this effect modified by metabolic syndrome?
RCT (n=4,715)
randomized
Does clopidogrel-aspirin therapy reduce new stroke compared to aspirin alone in patients with mild ischemic stroke or high-risk transient ischemic attack, and is this effect modified by metabolic syndrome?
Effect estimate: HR 1.39 (95% CI 1.06-1.82)
p-value: p=0.02
In patients with mild ischemic stroke or high-risk TIA, metabolic syndrome increases the risk of recurrent stroke but does not attenuate the efficacy or safety of dual antiplatelet therapy with clopidogrel and aspirin.
Metabolic syndrome identifies higher recurrent stroke risk after mild ischemic stroke or TIA; confirms clopidogrel-aspirin efficacy is unmodified by metabolic status.
Background Metabolic syndrome (MetS) attenuates antiplatelet agent effects. This study investigated the efficacy and safety of clopidogrel–aspirin therapy for secondary stroke prevention in patients with MetS. Methods Data were obtained from the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High‐Risk Intracranial or Extracranial Atherosclerosis) trial. Patients with mild ischemic stroke or high‐risk transient ischemic attack were randomized to treatment with clopidogrel–aspirin or aspirin alone within 72 hours after symptom onset. MetS was defined according to the Adult Treatment Panel‐III. The primary efficacy outcome was new stroke, and the primary safety outcome was moderate ‐ to ‐ severe bleeding within 90‐day follow‐up. Differences between groups were estimated with Cox proportional hazards models, with hazard ratio (HR) and 95% CI presented. Results This study included 4715 patients, with a mean age of 63.7±9.6 years, 35.8% of women, and 75.8% of patients having MetS. After adjustment for potential confounders, patients with MetS were at higher risk of recurrent stroke (HR, 1.39 [95% CI, 1.06–1.82]; P =0.02) but not moderate ‐ to ‐ severe bleeding events (HR, 1.02 [95% CI, 0.47–2.21]; P =0.97) as compared with patients without MetS. However, MetS state did not impact the efficacy of clopidogrel–aspirin therapy for recurrent stroke ( P for interaction=0.44) and the safety for moderate‐to‐severe bleeding events ( P for interaction=0.54). Conclusions MetS was associated with higher risk of recurrent stroke at 90 days. There was no difference in the effect of clopidogrel–aspirin therapy on reducing new stroke and increasing moderate‐to‐severe bleeding events between patients with and without MetS. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03635749.
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Zhang et al. (2025) conducted an RCT in Mild ischemic stroke or transient ischemic attack with Metabolic Syndrome (n=4,715). clopidogrel-aspirin therapy vs. aspirin alone was evaluated on recurrent stroke (HR 1.39, 95% CI 1.06-1.82, p=0.02). Metabolic syndrome was associated with a higher risk of recurrent stroke at 90 days (HR 1.39; 95% CI 1.06-1.82; P=0.02), but did not alter the efficacy of clopidogrel-aspirin therapy.
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