Systemic Thrombolysis by Alteplase for Acute Ischemic Stroke

Darvesh, Nazia; Butcher, Robyn

doi:10.51731/cjht.2022.351

Cited by 3 publications

(4 citation statements)

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“…[23][24][25] Unlike the clinical practice guidelines, regulatory approval for intravenous alteplase use in patients with acute ischemic stroke is restricted to patients presenting within 3 hours of stroke symptom onset. 10,11 This key secondary analyses from the AcT trial aims to therefore present in detail the effect of tenecteplase versus alteplase in the early versus late (3-4.5 hours) presenters while also assessing if the well-known relationship of time to thrombolysis on outcomes with alteplase is also seen with tenecteplase.…”

Section: Discussionmentioning

confidence: 99%

“…9 Moreover, with regulatory approval for alteplase restricted to patients presenting within 3 hours of acute ischemic stroke onset, the effect of thrombolysis with tenecteplase versus alteplase in acute ischemic stroke patients presenting beyond 3 hours is also not understood well. 10,11 Moreover, pharmacokinetic differences between tenecteplase and alteplase (fibrin specificity and half-life) along with recent trial data suggesting to potentially higher early recanalization rates with tenecteplase could mean that the effect of time to treatment on outcomes may be different between tenecteplase and alteplase. [5][6][7] The aim of this study was therefore to present the effect of thrombolysis with tenecteplase versus alteplase on clinical outcomes in the early (0-to 3-hour time window) versus the late (3-to 4.5-hour time window) presenting patients enrolled in the AcT RCT.…”

mentioning

confidence: 99%

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Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial

Singh,

Almekhlafi,

Bala

et al. 2023

Stroke

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BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time ( P interaction =0.161) or door-to-needle time ( P interaction =0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic.clinicaltrials.gov ; Unique identifier: NCT03889249.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial

Singh,

Almekhlafi,

Bala

et al. 2023

Stroke

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“…14 Several problematic trials to imply uncertainty of the benefit of alteplase within the 0-to 3-hour treatment window were included in the rapid review. (1) The PRISMS trial, 20 a trial on non-disabling deficits, which as mentioned above is not an indication for alteplase. (2) A NINDS retrospective subgroup analysis 21 of 58 patients with mild strokes (NIHSS 5 or less).…”

Section: Efficacy Of Alteplase Within 3 Hours Of Symptom Onsetmentioning

confidence: 99%

Letter to the Editor Regarding CADTH rapid review: Systemic Thrombolysis by Alteplase for Acute Ischemic Stroke

Micieli¹,

Krawczyk²,

Hunter³

et al. 2022

cjht

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The Canadian Stroke Consortium read with interest the recent rapid review by CADTH on the evidence of alteplase for acute ischemic stroke. We felt it necessary to reply for several reasons: despite the 27-year history of alteplase since the NINDS publication, the rapid review limits the search to the last 6 years, which does not reflect the totality of the evidence, the process for inclusion of studies was questionable, leading to a strongly biased representation of the existing literature, and important concerns from the single expert reviewer were not adequately addressed prior to publication.

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“…Although the effect of time to treatment with alteplase on clinical outcomes is well known, with the phrase "Time is Brain" having become a key messaging strategy for acute stroke thrombolysis, the nature of this relationship in patients administered tenecteplase has yet to be described 8 . Moreover, with regulatory approval for alteplase restricted to patients presenting within 3 hours of acute ischemic stroke onset, the effect of thrombolysis with tenecteplase vs. alteplase in acute ischemic stroke patients presenting beyond 3 hours is also not understood well 9,10 . The aim of this study was therefore to present the effect of thrombolysis with tenecteplase vs. alteplase on clinical outcomes in the early (0-3-hour time window) vs. the late (3-4.5-hour time window) presenting patients enrolled in the AcT RCT.…”

Section: Introductionmentioning

confidence: 99%

Effect of Time to Thrombolysis on Clinical Outcomes in Patients with Acute Ischemic Stroke Treated with Tenecteplase Compared to Alteplase: Analysis from the AcT Randomized Controlled Trial

Singh

Almekhlafi

Bala

et al. 2023

Preprint

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Background: The Alteplase compared to Tenecteplase (AcT) randomized controlled trial (RCT) showed that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known, however the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. Methods: Patients included were from AcT, a pragmatic, registry linked, phase 3 RCT comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4·5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin scale(mRS) 0-1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality rates. Mixed effects logistic regression was used to assess a)the association of stroke symptom onset to needle time (ONT), b)door (hospital arrival) to needle time(DNT) with outcomes and c)if these associations were modified by type of thrombolytic administered( tenecteplase vs. alteplase), after adjusting for age, sex, baseline stroke severity and site of intracranial occlusion. Results: Of the 1538 patients included in this analysis, 1146(74.5%)[591: tenecteplase, 555 alteplase] presented within 3 hours vs. 392 (25.5%)[196: TNK, 196 alteplase] who presented within 3-4.5 hours of symptom onset. Baseline patient characteristics in the 0-3 hour versus 3-4.5-hour time window were similar, except patients in the 3-to-4.5-hour window had lower median baseline NIHSS (10 vs 7 respectively) and lower proportion of patients with large vessel occlusion on baseline CT Angiography (26.9% vs 18.7% respectively). Type of thrombolytic agent ( tenecteplase vs. alteplase) did not modify the association between ONT(pinteraction = 0.161) or DNT(pinteraction = 0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-min reduction in ONT was associated with a 1.8% increase while every 10 min reduction in DNT was associated with a 0.2% increase in the probability of achieving 90-day mRS 0-1 respectively. Conclusion: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.

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Systemic Thrombolysis by Alteplase for Acute Ischemic Stroke

Cited by 3 publications

References 0 publications

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial

Letter to the Editor Regarding CADTH rapid review: Systemic Thrombolysis by Alteplase for Acute Ischemic Stroke

Effect of Time to Thrombolysis on Clinical Outcomes in Patients with Acute Ischemic Stroke Treated with Tenecteplase Compared to Alteplase: Analysis from the AcT Randomized Controlled Trial

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