Effect of Stroke Severity on Efficacy and Safety of Indobufen versus Aspirin in Patients with Moderate to Severe Stroke: Results from the INSURE Randomized Clinical Trial.

Aims: Stroke severity may affect the benefits and safety of antiplatelet therapies. We aimed to investigate whether the efficacy and safety of indobufen versus aspirin were affected by stroke severity.

Methods: We compared the efficacy and safety of indobufen versus aspirin in patients with NIHSS scores of 4-6, 7-9, and 10-18. The primary efficacy outcome was new stroke (ischemic or hemorrhagic) within 90 days, and the primary safety outcome was moderate or severe bleeding within 90 days. The non-inferiority criteria were set at 1.25 for the upper bounds of the 95% CI of the HR for indobufen versus aspirin based on the statistical analysis of the primary clinical trial.

Results: In total, 3921 patients presented with NIHSS scores of 4-6, 998 patients presented with NIHSS scores of 7-9, and 515 patients presented with NIHSS scores of 10-18. The risk of the primary outcome among patients with NIHSS scores of 4-6 was higher in indobufen group than that in aspirin group (HR, 1.62; 95% CI, 1.26 to 2.08). However, indobufen was non-inferior to aspirin in patients with NIHSS scores of 7-9 (HR, 0.66; 95% CI, 0.38 to 1.15; non-inferiority P = 0.01) and NIHSS scores of 10-18 (HR, 0.49; 95% CI, 0.23 to 1.05; non-inferiority P = 0.008), with a significant statistical interaction (P = 0.001). Moderate or severe bleeding risk differences between treatments did not vary with stroke severity.

Conclusions: This exploratory analysis indicates that the benefit of indobufen in reducing new strokes within 3 months may vary across stroke severity. The potential non-inferiority of indobufen relative to aspirin in patients with NIHSS scores of ≥ 7, with no significant difference in safety, requires further study.