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

Abstract

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.