Bridging thrombolysis with tenecteplase versus endovascular thrombectomy alone for large-vessel anterior circulation stroke: a target trial emulation analysis

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; Urs Fischer

doi:10.1136/jnnp-2024-335325

Bridging thrombolysis with tenecteplase versus endovascular thrombectomy alone for large-vessel anterior circulation stroke: a target trial emulation analysis

J Neurol Neurosurg Psychiatry. 2025 Jan 22:jnnp-2024-335325. doi: 10.1136/jnnp-2024-335325. Online ahead of print.

Authors

Valerian L Altersberger^{1

2}, Johannes Kaesmacher³, Leonid Churilov⁴, Vignan Yogendrakumar^{4

5}, Jan Gralla³, Daniel Strbian⁶, David J Seiffge⁷, Peter J Mitchell⁸, Timothy J Kleinig⁹, Bruce Cv Campbell⁴, Urs Fischer^{2

7}

Affiliations

¹ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia valerian.altersberger@mh.org.au.
² Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
³ University Institute of Diagnostic and Interventional Neuroradiology, University Hospital of Bern, Inselspital, University of Bern, Bern, Switzerland.
⁴ Department of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
⁵ Division of Neurology, The Ottawa Hospital and Ottawa Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
⁶ Department of Neurology, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.
⁷ Department of Neurology, University Hospital of Bern, University of Bern, Bern, Switzerland.
⁸ Department of Radiology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁹ Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

PMID: 39848674
DOI: 10.1136/jnnp-2024-335325

Abstract

Background: Whether bridging thrombolysis with tenecteplase is beneficial compared with thrombectomy alone in patients who had a stroke with large-vessel occlusion remains unclear.

Methods: This 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).

Results: Of 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.

Conclusion: Tenecteplase 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.

Keywords: CEREBROVASCULAR DISEASE; STROKE.