Tenecteplase Shows Similar Profile to Alteplase as First-Line Treatment for Large Vessel Occlusion Stroke

Article

Tenecteplase, a genetically modified molecule of alteplase, had similar benefit and safety as alteplase, and was not modified by baseline occlusion site.

Fouzi Bala, MD, MSc, diagnostic and interventional neuroradiologist, Centre Hospitalier Universitaire de Tours

Fouzi Bala, MD, MSc

Recently published data from a prespecified secondary analysis of the phase 3 ACT randomized controlled trial showed similar reperfusion, safety, and functional outcomes in patients with large vessel occlusion (LVO) stroke treated with either tenecteplase or alteplase. Overall, the findings suggest that tenecteplase could be used as a first-line thrombolytic agent for this patient population.

Published in JAMA Neurology, the trial randomized 1600 individuals, 520 of which were included in the final analysis (tenecteplase: n = 263; alteplase: n = 257). All patients presented within 4.5 hours of symptoms following their stroke. At 90 days, the rates of modified Rankin Scale (mRS) scores between 0-2 (49% vs 51%) symptomatic intracerebral hemorrhage (4.1% vs 4.3%) and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively.

Led by Fouzi Bala, MD, MSc, diagnostic and interventional neuroradiologist, Centre Hospitalier Universitaire de Tours, the study used proportion of patients with mRS scores of 0-1 at 90 days as the primary end point, with several other secondary outcomes included. Among the analyzed cohort, 135 (26.0%) had LVO with intracranial internal carotid artery (ICA) occlusion, 237 (45.6%) with M1-middle cerebral artery (MCA), 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. Both delivered intravenously, tenecteplase was given in doses of 0.25 mg/kg while alteplase was administered at doses of 0.9 mg/kg.

Only patients with LVO were included in the substudy. At the conclusion of the analysis, findings showed that 32.7% (n = 86) of patients in the Tenecteplase group had mRS score of 0 to 1 at 90 to 120 days vs 29.6% (n = 76) of those in the alteplase group (adjusted rate ratio [aRR], 1.15; 95% CI, 0.98-1.35). Rates of functional independence, indicated by mRS scores of 0-2, and return to baseline function, were not different between groups.

On angiographic outcomes (n = 405), no differences were noted in successful reperfusion on first and final angiographic images. Successful arterial recanalization rates, indicated by revised arterial occlusion (rAOL) scale scores greater than 2b, were comparable between treatment groups (tenecteplase: 17.5% vs alteplase: 14.6%; aRR, 1.21; 95% CI, 0.75-1.93).

In terms of specific occlusion location, the proportion of patients who achieved mRS scores between 0 and 1 at 90 to 120 days was 26.1% vs 18.2% in those with ICA occlusion (P = .30) and 34.7% vs 30.2% in M1-MCA occlusion (P = .49) in the Tenecteplase and alteplase treatment groups, respectively. Across both the tenecteplase and alteplase groups, investigators observed similar proportions of mRS 0-1 in patients with M2-MCA (33.9% vs 36.5%; P = .85) and basilar occlusions (45.4% vs 45.0%; P = .99).

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Across all location subgroups, the rates of successful reperfusion (eTICI score 2b-3) on the first and final angiographic acquisitions were similar between treatment arms. No interaction between occlusion location and treatment group were found. Furthermore, investigators observed no treatment difference in the proportion of symptomatic intracerebral hemorrhage based on location subgroup (ICA occlusion: 7.2% vs 3.0%; P = .44; M1-MCA: 2.5% vs 4.2%; P = .72; MC-MCA: 10.7% vs 5.8%; P = .51; basilar subgroup: 9.1% vs 5.0%; P = .99).

In a subgroup of 112 patients treated with intravenous thrombolysis alone without endovascular thrombectomy, functional and safety outcomes were similar in a univariable analysis. Despite this, after adjusting for confounders, patients who received tenecteplase had higher odds of mRS scores of 0 to 1 at 90 days (aRR, 2.01; 95% CI, 1.21-3.30) compared with the alteplase group.

"From an emergency workflow perspective, times from thrombolysis administration to reperfusion assessment in patients en route to EVT were not different between the 2 thrombolytic agents," the study authors wrote. "However, the reports of shorter workflow times in tenecteplase vs alteplase were mainly noted in patients from the drip-and-ship paradigm."

They continued, "For example, in the pooled EXTEND-IA trials, 64% of patients receiving alteplase and 42% of those receiving tenecteplase were transferred from a primary stroke center. In our substudy, only 30 patients (5.7%) were transferred from a primary stroke center. Because of its ease of administration, it is possible that tenecteplase may make acute stroke workflow more efficient, especially in patients who are candidates for EVT."

REFERENCE
1. Bala F, Singh N, Buck B, et al. Safety and efficacy of tenecteplase compared with alteplase in patients with large vessel occlusion stroke: a prespecified secondary analysis of the ACT randomized clinical trial. JAMA Neurol. Published online July 10, 2023. doi:10.1001/jamaneurol.2023.2094
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