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Updated: Jun 30, 2025
Optimized Management of Endovascular Treatment for Acute Ischemic Stroke
Published on: January 18, 2018
Association of Time to Thrombolysis With Early Reperfusion After Alteplase and Tenecteplase in Patients With Large
Vignan Yogendrakumar1, James Beharry1, Leonid Churilov1
1From the Department of Medicine and Neurology (V.Y., J.B., L.C., L.P., K.A., M.U., L.W., N.Y., B.Y., G.J.S., M.W.P., G.A.D., S.M.D., B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia; Department of Neurology (J.B., T.Y.W.), Christchurch Hospital, New Zealand; Department of Radiology (P.J.M., B.Y., P.D.), Royal Melbourne Hospital, University of Melbourne, Parkville; Department of Neurology (T.J.K.), Royal Adelaide Hospital; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research; Florey Institute of Neuroscience and Mental Health (V.N.T.), University of Melbourne, Parkville; Department of Neurology (H.B.), Princess Alexandra Hospital, Brisbane, Queensland; Eastern Health and Eastern Health Clinical School (H.M.D.), Department of Neurosciences, Monash University, Clayton, Victoria; Melbourne Medical School (T.W.), Department of Medicine and Neurology, The University of Melbourne and Western Health, Sunshine Hospital, St Albans Victoria; and Department of Neurology (M.W.P.), Liverpool Hospital, University of New South Wales, Sydney, Australia.
Background And Objectives:
Early treatment with intravenous alteplase increases the probability of lytic-induced reperfusion in large vessel occlusion (LVO) patients. The relationship of tenecteplase-induced reperfusion and the timing of thrombolytic administration has not been explored. In this study, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates and assessed their relationship to the time of thrombolytic administration.
Methods:
Patients who were initially treated with a thrombolytic within 4.5 hours of symptom onset were pooled from the Royal Melbourne Stroke Registry, EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK part 2 trials. The primary outcome, thrombolytic-induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at initial angiographic assessment (or repeat CT perfusion/angiography). We compared the treatment effect of tenecteplase and alteplase through fixed-effects Poisson regression modelling.
Results:
Among 846 patients included in the primary analysis, early reperfusion was observed in 173 (20%) patients (tenecteplase: 98/470 [21%], onset-to-thrombolytic time: 132 minutes [interquartile range (IQR): 99-170], and thrombolytic-to-assessment time: 61 minutes [IQR: 39-96]; alteplase: 75/376 [19%], onset-to-thrombolytic time: 143 minutes [IQR: 105-180], thrombolytic-to-assessment time: 92 minutes [IQR: 63-144]). Earlier onset-to-thrombolytic administration times were associated with an increased probability of thrombolytic-induced reperfusion in patients treated with either tenecteplase (adjusted risk ratio [aRR] 1.05 per 15 minutes [95% confidence interval (CI) 1.00-1.12] or alteplase (aRR 1.06 per 15 minutes [95% CI 1.00-1.13]). Tenecteplase remained associated with higher rates of reperfusion vs alteplase after adjustment for onset-to-thrombolytic time, occlusion site, thrombolytic-to-assessment time, and study as a fixed effect, (adjusted incidence rate ratio: 1.41 [95% CI 1.02-1.93]). No significant treatment-by-time interaction was observed (p = 0.87).
Discussion:
In patients with LVO presenting within 4.5 hours of symptom onset, earlier thrombolytic administration increased successful reperfusion rates. Compared with alteplase, tenecteplase was associated with a higher probability of lytic-induced reperfusion, independent of onset-to-lytic administration times.
Trial Registration Information:
ClinicalTrials.gov Identifiers: NCT02388061, NCT03340493.
Classification Of Evidence:
This study provides Class II evidence that among patients with LVO receiving a thrombolytic, reperfusion was more likely with tenecteplase than alteplase.
