Dataset Information

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.

ABSTRACT:

Importance

It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke.

Objective

To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke.

Design, setting, and participants

This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent.

Exposures

Intravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg).

Main outcomes and measures

The primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out.

Results

Among 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy.

Conclusions and relevance

The findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.

SUBMITTER: Bala F

PROVIDER: S-EPMC10334294 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

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.

Bala Fouzi F Singh Nishita N Buck Brian B Ademola Ayoola A Coutts Shelagh B SB Deschaintre Yan Y Khosravani Houman H Appireddy Ramana R Moreau Francois F Phillips Stephen S Gubitz Gord G Tkach Aleksander A Catanese Luciana L Dowlatshahi Dar D Medvedev George G Mandzia Jennifer J Pikula Aleksandra A Shankar Jai Jai JJ Williams Heather H Field Thalia S TS Manosalva Alzate Alejandro A Siddiqui Muzaffar M Zafar Atif A Imoukhoude Oje O Hunter Gary G Alhabli Ibrahim I Benali Faysal F Horn MacKenzie M Hill Michael D MD Shamy Michel M Sajobi Tolulope T TT Swartz Richard H RH Menon Bijoy K BK Almekhlafi Mohammed M

JAMA neurology 20230801 8

<h4>Importance</h4>It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke.<h4>Objective</h4>To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke.<h4>Design, setting, and participants</h4>This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) r ...[more]

PMID: 37428494

Similar Datasets

Project description:BackgroundCarotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion.AimsWe investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL.MethodsThis is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed.ResultsAmong 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group.ConclusionIn patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.

Project description:IntroductionIn 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 methodsThis 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.ResultsAmong 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.ConclusionIn 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 registrationClinicalTrials.gov Identifier: NCT05809921.

Project description:ImportanceTenecteplase is an alternative to alteplase for emergency treatment of acute ischemic stroke. However, limited data are available comparing their clinical effectiveness in routine clinical practice.ObjectiveTo compare short-term effectiveness and safety outcomes for patients with ischemic stroke treated with intravenous tenecteplase vs alteplase.Design, setting, and participantsThis comparative effectiveness study used data prospectively collected from July 1, 2020, through June 30, 2022, from the Get With The Guidelines-Stroke registry.ExposureConsecutive patients with ischemic stroke treated with either tenecteplase or alteplase within 4.5 hours from last known well time were included.Main outcomes and measuresThe primary end point was functional independence on discharge (modified Rankin Scale [mRS] score, 0-2). Secondary effectiveness end points included disability free at discharge (mRS score, 0-1), discharge home, and independent ambulation at discharge. Safety end points included symptomatic intracranial hemorrhage (sICH) within 36 hours and combined in-hospital mortality or hospice discharge. Generalized linear mixed models were fit to evaluate associations between exposure to tenecteplase (vs alteplase) and end points after adjustment for demographic, clinical, and hospital-level variables. Adjusted odds ratios (AORs) with 95% CIs were computed.ResultsAmong 79 550 patients treated with intravenous thrombolysis, the mean (SD) age was 68.6 (14.8) years, 38 596 (48.5%) were female, and the median National Institutes of Health Stroke Scale (NIHSS) score was 7 (IQR, 4-13). Of these patients, 9465 (11.9%) received tenecteplase (mean [SD] age, 69.6 [14.7] years; median NIHSS score, 7 [IQR, 4-14]; 4504 [47.6%] female) and 70 085 (88.1%) received alteplase (mean [SD] age, 68.5 [14.8] years; median NIHSS score, 7 [IQR, 4-13]; 34 092 [48.6%] female). After adjustment for covariates, no significant differences were found between tenecteplase and alteplase in effectiveness or safety outcomes for the overall cohort, including functional independence at discharge (AOR, 1.00; 95% CI, 0.93-1.07), sICH (AOR, 0.96; 95% CI, 0.83-1.11), and in-hospital mortality or hospice discharge (AOR, 0.98; 95% CI, 0.89-1.07), but significant improvement was found in discharge home (AOR, 1.26; 95% CI, 1.03-1.53), in-hospital mortality (AOR, 0.63; 95% CI, 0.47-0.85), and composite in-hospital mortality or hospice discharge (AOR, 0.78; 95% CI, 0.62-0.97) among those who were eligible for but did not undergo endovascular thrombectomy.Conclusions and relevanceThis large, nationwide comparative effectiveness study using data from routine clinical practice demonstrated similar effectiveness and safety outcomes with tenecteplase compared with alteplase in patients with acute ischemic stroke. This study supports tenecteplase as a reasonable alternative to alteplase.

Project description:BackgroundRecent randomized trials have suggested that endovascular thrombectomy (EVT) alone may provide similar functional outcomes as the current standard of care, EVT combined with intravenous alteplase treatment, for acute ischemic stroke secondary to large vessel occlusion. We conducted an economic evaluation of these 2 therapeutic options.MethodsWe constructed a decision analytic model with a hypothetical cohort of 1000 patients to assess the cost-effectiveness of EVT with intravenous alteplase treatment versus EVT alone for acute ischemic stroke secondary to large vessel occlusion from both the societal and public health care payer perspectives. We used studies and data published in 2009-2021 for model inputs, and acquired cost data for Canada and China, representing high- and middle-income countries, respectively. We calculated incremental cost-effectiveness ratios (ICERs) using a lifetime horizon and accounted for uncertainty using 1-way and probabilistic sensitivity analyses. All costs are reported in 2021 Canadian dollars.ResultsIn Canada, the difference in quality-adjusted life-years (QALYs) gained between EVT with alteplase and EVT alone was 0.10 from both the societal and health care payer perspectives. The difference in cost was $2847 from a societal perspective and $2767 from the payer perspective. In China, the difference in QALYs gained was 0.07 from both perspectives, and the difference in cost was $1550 from the societal perspective and $1607 from the payer perspective. One-way sensitivity analyses showed that the distributions of modified Rankin Scale scores at 90 days after stroke were the most influential factor on ICERs. For Canada, compared to EVT alone, the probability that EVT with alteplase would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained was 58.7% from a societal perspective and 58.4% from a payer perspective. The corresponding values for at a willingness-to-pay threshold of $47 185 (3 times the Chinese gross domestic product per capita in 2021) were 65.2% and 67.4%.InterpretationFor patients with acute ischemic stroke due to large vessel occlusion eligible for immediate treatment with both EVT alone and EVT with intravenous alteplase treatment, it is uncertain whether EVT with alteplase is cost-effective compared to EVT alone in Canada and China.

Dataset Information

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.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

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.

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