Intracranial Hemorrhage Patterns and Outcomes in Minor Stroke: Analysis of the TEMPO-2 Trial

BACKGROUND: – Intracranial hemorrhage (ICH) negatively impacts functional outcomes after ischemic stroke, with potentially disproportionate impacts in patients with minor stroke. This study aimed to evaluate the effect of ICH on outcomes in minor ischemic stroke and to identify predictors associated with ICH. METHODS: – This was a secondary analysis of the TEMPO-2 multicenter, randomized trial, which compared tenecteplase with nonthrombolytic standard care in patients within 12 hours of symptom onset with minor stroke (National Institutes of Health Stroke Scale score ≤5) and a visible vessel occlusion or perfusion mismatch. Follow-up imaging was assessed for hemorrhage using the Heidelberg classification. Symptomatic ICH was defined as any hemorrhage associated with neurological deterioration. The primary outcome was return to premorbid functional status at 90 days, measured using the modified Rankin Scale. Mixed-effects regression was used to assess the effect of ICH status on outcomes, adjusting for treatment, age, sex, baseline stroke severity, and onset-to-randomization time, with region included as a random effect. RESULTS: – Among 884 participants, 865 had complete 24-hour imaging and follow-up. Using complete case analysis (n=865), any ICH occurred in 102 participants (11.8%). Patients with any ICH (median age, 70 years; 35.3% females) more frequently had premorbid hypertension (71.6% versus 57.7%) and atrial fibrillation (28.4% versus 18.1%). Any ICH was not associated with reduced odds of returning to baseline neurological function (adjusted odds ratio, 0.93 [95% CI, 0.87–1.00]) but was associated with higher 90-day mortality (9.8% versus 1.8%; adjusted hazard ratio, 3.71 [95% CI, 1.54–8.95]). Rates of any ICH were higher in tenecteplase than standard care (14.4% versus 9.2%; P=0.02), although most were petechial hemorrhagic transformations. Symptomatic ICH rates, although numerically higher, were not significantly different between the tenecteplase versus control arms (8 [1.9%] versus 2 [0.5%]; P=0.06). CONCLUSIONS: – Although most hemorrhages were minor, the presence of any ICH was strongly associated with increased mortality, highlighting that even minor hemorrhagic transformation may be prognostically significant in patients with minor ischemic stroke.