Tenecteplase Improves Reperfusion across Time in Large Vessel Stroke

• Published in: Annals of neurology 2023-03, Vol.93 (3), p.489-499
• Main Authors: Yogendrakumar, Vignan, Beharry, James, Churilov, Leonid, Alidin, Khairunnisa, Ugalde, Melissa, Pesavento, Lauren, Weir, Louise, Mitchell, Peter J., Kleinig, Timothy J., Yassi, Nawaf, Thijs, Vincent, Wu, Teddy Y., Shah, Darshan G., Dewey, Helen M., Wijeratne, Tissa, Yan, Bernard, Desmond, Patricia M., Sharma, Gagan, Parsons, Mark W., Donnan, Geoffrey A., Davis, Stephen M., Campbell, Bruce C. V.
• Format: Article
• Language: English
• Subjects: Brain Ischemia - drug therapy; Cardiovascular system; Cerebral blood flow; Clinical trials; Comparative analysis; Fibrinolytic Agents - therapeutic use; Humans; Ischemia; Occlusion; Patients; Reperfusion; Reperfusion - methods; Segments; Statistical analysis; Stroke; Stroke - drug therapy; Subgroups; Tenecteplase - therapeutic use; Thrombolysis; Thrombosis; Tissue Plasminogen Activator; Treatment Outcome
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.26547

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