Abstract Body: Introduction: The tenecteplase versus standard of care for minor ischemic stroke with proven occlusion (TEMPO-2) trial showed that patients presenting with minor deficits up to 12 h do not benefit from intravenous thrombolysis. The trial included patients with minor but disabling deficits, mainly beyond 4.5 h, if they were not eligible for standard-of-care thrombolysis. We aimed to determine if intravenous tenecteplase improves outcomes in this subgroup of TEMPO-2 patients with disabling deficits.
Methods: This was an exploratory secondary analysis of the TEMPO-2 trial, which randomized patients across 48 hospitals globally with minor acute ischemic stroke (NIHSS score 0-5) and intracranial occlusion or focal perfusion abnormality within 12 h from stroke onset to intravenous tenecteplase (0.25 mg/kg) or non-thrombolytic standard of care. Adopting an available definition for disabling stroke from the TREAT Task Force consensus (Table 1), we compared efficacy and safety outcomes between treatment arms for participants with non-disabling versus disabling syndromes at presentation.
Results: Among 886 patients, 786 (88.7%) and 100 (11.3%) were identified to have non-disabling and disabling deficits, respectively. Patients with disabling deficits had higher baseline NIHSS scores (4 vs 2, P<0.001), later presentations (288min vs 133min, P<0.001) and longer onset to treatment time (411min vs 278min, P<001). There was no evidence of treatment effect heterogeneity between disabling and non-disabling groups (P_interaction = 0.22). However, there were nominally fewer excellent outcomes at 90 days (mRS 0-1) with tenecteplase compared with standard of care in the disabling group (non-disabling: 72.0% vs 72.5%, P=0.936; disabling: 47.2% vs 61.7%, P=0.164). No difference in symptomatic ICH was found but an interaction existed with treatment arms and presence of disabling stroke regarding any hemorrhage on follow-up neuroimaging (non-disabling: tenecteplase 13.5% vs control 10.0%, P=0.146; disabling: tenecteplase 20.8% vs control 2.1%, P=0.005. P_interaction = 0.049).
Conclusions: The TREAT Task Force definition of disabling stroke did not modify the neutral treatment effect of intravenous tenecteplase in patients with minor stroke and intracranial occlusion. Fewer excellent outcomes after intravenous tenecteplase were observed in the disabling deficits group, possibly due to longer times to presentation and thrombolysis for the disabling subgroup.