Tenecteplase Improves Reperfusion across Time in Large Vessel Stroke

Abstract

Objective Tenecteplase improves reperfusion compared to alteplase in patients with large vessel occlusions. To determine whether this improvement varies across the spectrum of thrombolytic agent to reperfusion assessment times, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates. Methods Patients with large vessel occlusion and treatment with thrombolysis were pooled from the Melbourne Stroke Registry, and the EXTEND‐IA and EXTEND‐IA TNK trials. The primary outcome, thrombolytic‐induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at imaging reassessment. We compared the treatment effect of tenecteplase and alteplase, accounting for thrombolytic to assessment exposure times, via Poisson modeling. We compared 90‐day outcomes of patients who achieved reperfusion with a thrombolytic to patients who achieved reperfusion via endovascular therapy using ordinal logistic regression. Results Among 893 patients included in the primary analysis, thrombolytic‐induced reperfusion was observed in 184 (21%) patients. Tenecteplase was associated with higher rates of reperfusion (adjusted incidence rate ratio [aIRR] = 1.50, 95% confidence interval [CI] = 1.09–2.07, p = 0.01). Findings were consistent in patient subgroups with first segment (aIRR = 1.41, 95% CI = 0.93–2.14) and second segment (aIRR = 2.07, 95% CI = 0.98–4.37) middle cerebral artery occlusions. Increased thrombolytic to reperfusion assessment times were associated with reperfusion (tenecteplase: adjusted risk ratio [aRR] = 1.08 per 15 minutes, 95% CI = 1.04–1.13 vs alteplase: aRR = 1.06 per 15 minutes, 95% CI = 1.00–1.13). No significant treatment‐by‐time interaction was observed (p = 0.87). Reperfusion via thrombolysis was associated with improved 90‐day modified Rankin Scale scores (adjusted common odds ratio = 2.15, 95% CI = 1.54–3.01) compared to patients who achieved reperfusion following endovascular therapy. Interpretation Tenecteplase, compared to alteplase, increases prethrombectomy reperfusion, regardless of the time from administration to reperfusion assessment. Prethrombectomy reperfusion is associated with better clinical outcomes. ANN NEUROL 2023;93:489–499

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke

“…Early recanalization rates with alteplase in this study are similar to those reported in the Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography (INTERRSECT) study 5 (ie, 13%). These findings are also consistent with a French multicenter study 7 of 262 patients and the pooled analysis 21 of EXTEND IA and EXTEND IA TNK trials and the Melbourne Stroke Registry, which found similar rates of early reperfusion in both thrombolytic agents (21% vs 18% and 21% vs 19%, respectively). A large proportion of patients in these studies were transferred from a primary stroke center (drip-and-ship paradigm) and had long times from thrombolytic administration to reperfusion assessment.…”

“…This has potentially contributed to the higher reperfusion rates overall for both thrombolytic agents and for the reported difference between treatment groups . Of note, median (IQR) time from thrombolysis to reperfusion assessment in our study was 53 (35-77) minutes (Table 1) vs 76 (48-125) minutes in the pooled Australian data . The differences in early recanalization vs early reperfusion rates in this study are expected, as thrombolysis could result in thrombus migration to major distal branches without corresponding improvement in reperfusion, especially soon after lytic administration .…”

“…A large proportion of patients in these studies were transferred from a primary stroke center (drip-and-ship paradigm) and had long times from thrombolytic administration to reperfusion assessment. This has potentially contributed to the higher reperfusion rates overall for both thrombolytic agents and for the reported difference between treatment groups . Of note, median (IQR) time from thrombolysis to reperfusion assessment in our study was 53 (35-77) minutes (Table 1) vs 76 (48-125) minutes in the pooled Australian data .…”

“…7,21 Of note, median (IQR) time from thrombolysis to reperfusion assessment in our study was 53 (35-77) minutes (Table 1) vs 76 (48-125) minutes in the pooled Australian data. 21 The differences in There was no significant difference between the tenecteplase and alteplase groups in the ordinal analysis of the mRS score, adjusted for age, sex, baseline stroke severity, occlusion location, and time from stroke symptom onset to needle as fixed-effects variables and site as a random-effects variable (adjusted common odds ratio, 0.91; 95% CI, 0.66-1.23). The mRS score ranges from 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability, 2 slight disability, 3 moderate disability, 4 moderately severe disability, 5 severe disability, and 6 death.…”

“…In our substudy, only 30 patients (5.7%) were transferred from a primary stroke center. 21 Because of its ease of administration, it is possible that tenecteplase may make acute stroke workflow more efficient, especially in patients who are candidates for EVT. 28…”