Dual Versus Mono Antiplatelet Therapy in Mild Versus Moderate Ischemic Stroke: A Post Hoc Analysis of the ATAMIS Randomized Trial

BACKGROUND: This prespecified post hoc analysis of the ATAMIS trial (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) aimed to investigate whether the benefit of dual antiplatelet therapy versus aspirin alone differs in patients with mild versus moderate stroke. METHODS: Using data from the modified intention‑to‑treat population of the ATAMIS trial, eligible patients were divided into mild (National Institutes of Health Stroke Scale [NIHSS] score 4–5) and moderate (NIHSS score 6–10) groups. The primary outcome was early neurological deterioration at 7 days, defined as an increase in the NIHSS score of ≥2 points from baseline. Safety outcomes included bleeding events and intracranial hemorrhage within 90 days. Binary logistic regression, Cox regression, and generalized linear models were used as appropriate. Adjusted models included age, sex, diabetes, hypertension, onset-to-treatment time, stroke cause, and other imbalanced baseline variables. Treatment-by-baseline stroke severity interaction was assessed. RESULTS: A total of 2915 patients were included, including 1992 (68.4%) with mild stroke and 923 (31.6%) with moderate stroke. Median age was 66 years (interquartile range, 59–73); 35.0% were women. Clopidogrel plus aspirin was associated with a significantly lower risk of early neurological deterioration compared with aspirin alone in the moderate stroke group (adjusted odds ratio, 0.31 [95% CI, 0.17–0.59]; P <0.001), whereas no significant difference was observed in the mild stroke group (adjusted odds ratio, 0.96 [95% CI, 0.66–1.41]; P =0.841). A significant interaction was identified between treatment effect and NIHSS score subgroup ( P interaction =0.003). The occurrence of bleeding events and intracranial hemorrhage was similar between treatment groups in both severity subgroups. CONCLUSIONS: In patients with acute mild-to-moderate ischemic stroke, the benefit of clopidogrel plus aspirin versus aspirin alone in preventing early neurological deterioration at 7 days may be greater among patients with moderate stroke (NIHSS score 6–10) than among those with mild stroke (NIHSS score 4–5), without an increased risk of bleeding. These findings suggest that baseline stroke severity may inform antiplatelet therapy selection, and warrant confirmation in future prospective studies. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02869009.