• Valerian L Altersberger, Johannes Kaesmacher, Leonid Churilov, Vignan Yogendrakumar, Jan Gralla, Daniel Strbian, David J Seiffge, Peter J Mitchell, Timothy J Kleinig, Bruce Cv Campbell, and Urs Fischer.
• Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia valerian.altersberger@mh.org.au.
• J. Neurol. Neurosurg. Psychiatr. 2025 Jan 22.

BackgroundWhether bridging thrombolysis with tenecteplase is beneficial compared with thrombectomy alone in patients who had a stroke with large-vessel occlusion remains unclear.MethodsThis is a causal inference study of observational data from the trials SWIFT DIRECT and EXTEND-IA TNK Parts 1 and 2 applying target trial emulation. We compared patients receiving thrombectomy alone to patients receiving tenecteplase 0.25 mg/kg or 0.40 mg/kg before thrombectomy. The primary outcome was functional independence (modified Rankin Scale (mRS) of 0-2) at 90 days. Secondary outcomes included improvement over the full ordinal mRS scale, freedom of disability (mRS 0-1), mortality and occurrence of symptomatic intracranial haemorrhage. The average causal treatment effect was estimated via inverse probability of treatment weighting and G-Computation. We calculated standardised risk differences (SRDs) and adjusted (common) ORs (a(c)ORs).ResultsOf 377 patients included in the target trial, 187 received thrombectomy alone and 190 tenecteplase before thrombectomy. Tenecteplase before thrombectomy did not increase the probability of patients achieving functional independence (SRD 0.04 (95% CI -0.06 to 0.13)) but resulted in a significant improvement in the mRS overall (acOR 1.56 (95% CI 1.07 to 2.23)) and in a higher probability of freedom from disability (SRD 0.10 (95% CI 0.01 to 0.20)). The probability for improvement of functional outcomes was further increased in patients treated within 140 min after onset (ordinal mRS acOR 1.63 (95% CI 1.04 to 2.56)). No significant differences in safety outcomes were observed between the two groups.ConclusionTenecteplase before thrombectomy compared with thrombectomy alone did not increase the probability of functional independence but resulted in significant improvement over the full mRS scale. This improvement was most evident in patients treated early.© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.

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