Second-dose intravenous thrombolysis with tenecteplase in alteplase-resistant medium-vessel-occlusion strokes: A retrospective and comparative study

Eur Stroke J. 2024 Dec;9(4):943-951. doi: 10.1177/23969873241254936. Epub 2024 Jun 3.

Abstract

Introduction: In intracranial medium-vessel occlusions (MeVOs), intravenous thrombolysis (IVT) shows inconsistent effectiveness and endovascular interventions remains unproven. We evaluated a new therapeutic strategy based on a second IVT using tenecteplase for MeVOs without early recanalization post-alteplase.

Patients and methods: This retrospective, comparative study included consecutively low bleeding risk MeVO patients treated with alteplase 0.9 mg/kg at two stroke centers. One center used a conventional single-IVT approach; the other applied a dual-IVT strategy, incorporating a 1-h post-alteplase MRI and additional tenecteplase, 0.25 mg/kg, if occlusion persisted. Primary outcomes were 24-h successful recanalization for efficacy and symptomatic intracranial hemorrhage (sICH) for safety. Secondary outcomes included 3-month excellent outcomes (modified Rankin Scale score of 0-1). Comparisons were conducted in the overall cohort and a propensity score-matched subgroup.

Results: Among 146 patients in the dual-IVT group, 103 failed to achieve recanalization at 1 h and of these 96 met all eligible criteria and received additional tenecteplase. Successful recanalization at 24 h was higher in the 146 dual-IVT cohort patients than in the 148 single-IVT cohort patients (84% vs 61%, p < 0.0001), with similar sICH rate (3 vs 2, p = 0.68). Dual-IVT strategy was an independent predictor of 24-h successful recanalization (OR, 2.7 [95% CI, 1.52-4.88]; p < 0.001). Dual-IVT cohort patients achieved higher rates of excellent outcome (69% vs 44%, p < 0.0001). Propensity score matching analyses supported all these associations.

Conclusion: In this retrospective study, a dual-IVT strategy in selected MeVO patients was associated with higher odds of 24-h recanalization, with no safety concerns. However, potential center-level confounding and biases seriously limit these findings' interpretation.

Trial registration: ClinicalTrials.gov Identifier: NCT05809921.

Keywords: Acute stroke; medium-vessel occlusion; tenecteplase; thrombolysis.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Administration, Intravenous
  • Aged
  • Aged, 80 and over
  • Female
  • Fibrinolytic Agents* / administration & dosage
  • Fibrinolytic Agents* / pharmacology
  • Fibrinolytic Agents* / therapeutic use
  • Humans
  • Ischemic Stroke / diagnostic imaging
  • Ischemic Stroke / drug therapy
  • Male
  • Middle Aged
  • Retrospective Studies
  • Stroke / diagnostic imaging
  • Stroke / drug therapy
  • Tenecteplase* / administration & dosage
  • Tenecteplase* / pharmacology
  • Tenecteplase* / therapeutic use
  • Thrombolytic Therapy* / methods
  • Tissue Plasminogen Activator* / administration & dosage
  • Tissue Plasminogen Activator* / pharmacology
  • Tissue Plasminogen Activator* / therapeutic use
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Tenecteplase
  • Tissue Plasminogen Activator

Associated data

  • ClinicalTrials.gov/NCT05809921