Association of Minimal Clinically Important Difference With Infarct Volume in Clinical Poststroke Outcomes.

BACKGROUND: Infarct volume is an imaging biomarker of ischemic tissue injury strongly correlated with poststroke outcomes and reperfusion benefit. We aimed to evaluate the follow-up infarct volume (FIV) difference corresponding to a 1%, 5%, and 10% increase in probability of excellent functional outcomes after intravenous thrombolysis. METHODS: Data are from the AcT trial (Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke). Patients with 24-hour infarct volume segmentations were included. The primary outcome was excellent functional outcome (modified Rankin Scale score=0-1). Associations between outcomes and FIV were investigated with regression analyses adjusted for covariates. Sensitivity analyses examined patients with noncontrast computed tomography versus magnetic resonance imaging follow-up and those treated versus not treated with endovascular thrombectomy. RESULTS: The study included 1478 patients (median age 74 years [interquartile range (IQR), 63-83], 48.2% female). Median FIV was 2.7 mL (IQR, 0-18.2), and 527 (35.7%) achieved excellent functional outcome. FIV was associated with excellent functional outcome: adjusted odds ratio, 0.97 (95% CI, 0.96-0.98) per 1-mL FIV increase. The median ΔFIV corresponding to a 1%, 5%, and 10% increase in adjusted probability of excellent functional outcomes were 1.5 mL (IQR, 1.4-1.9), 7.3 mL (IQR, 6.8-9.3), and 14.6 mL (IQR, 13.6-18.2), respectively. Results were consistent across follow-up imaging modality and endovascular thrombectomy subgroups. CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis, differences of ~1.5 mL, ~7 mL, and ~15 mL in FIV corresponded to a 1%, 5%, and 10% higher absolute probability of achieving excellent functional outcomes. These findings could inform the design of future clinical Phase 2 and proof-of-principle stroke trials that aim to use FIV as a key outcome measure.