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

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.

Graphical abstract

Figure 1.

Two representative cases of arterial occlusive lesion (AOL) classification at 1-h, based on thrombus change on gradient echo (GE) sequence. Patient 1: example of AOL 1 at 1 h. Initial MRI, DWI, FLAIR, GE and MRA (a–d, respectively). Control MRI 1 h after first alteplase-intravenous thrombolysis (IVT)-1 (e–h) shows minimal distal thrombus migration visible on GE sequence (g), with no significant change on MRA (h). Patient 2: example of partial recanalization (AOL-2) at 1 h. Initial MRI, DWI, FLAIR, GE, and MRA (i–l, respectively). Control MRI-2 1 h after IVT-1 (m–p) shows persistence of several “slow flows” on FLAIR (n) and significant change on MRA with smaller thrombus size (p) and distal downstream migration (o, arrow).

Figure 2.

Flow diagram of the study. AOL: arterial occlusive lesion; IVT: intravenous thrombolysis; MeVO-AIS: medium-vessel occlusion-acute ischemic stroke; MRI: magnetic resonance imaging.