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Replacing Alteplase with Tenecteplase: Is the Time Ripe?

ABSTRACT: Thrombolysis for acute ischemic stroke has predominantly been with alteplase for over a quarter of a century. In recent years, with trials showing evidence of higher rates of successful reperfusion, similar safety profile and efficacy of tenecteplase (TNK) as compared to alteplase, TNK has now emerged as another potential choice for thrombolysis in acute ischemic stroke. In this review, we will focus on these recent advances, aiming: (1) to provide a brief overview of thrombolysis in stroke; (2) to provide comparisons between alteplase and TNK for clinical, imaging, and safety outcomes; (3) to focus on key subgroups of interest to understand if there is an advantage of using TNK over alteplase or vice-versa, to review available evidence on role of TNK in intra-arterial thrombolysis, as bridging therapy and in mobile stroke units; and (4) to summarize what to expect in the near future from recently completed trials and propose areas for future research on this evolving topic. We present compelling data from several trials regarding the safety and efficacy of TNK in acute ischemic stroke along with completed yet unpublished trials that will help provide insight into these unanswered questions.

SUBMITTER: Singh N

PROVIDER: S-EPMC9911848 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Replacing Alteplase with Tenecteplase: Is the Time Ripe?

Singh Nishita N Menon Bijoy K BK Dmytriw Adam A AA Regenhardt Robert W RW Hirsch Joshua A JA Ganesh Aravind A

Journal of stroke 20230131 1

Thrombolysis for acute ischemic stroke has predominantly been with alteplase for over a quarter of a century. In recent years, with trials showing evidence of higher rates of successful reperfusion, similar safety profile and efficacy of tenecteplase (TNK) as compared to alteplase, TNK has now emerged as another potential choice for thrombolysis in acute ischemic stroke. In this review, we will focus on these recent advances, aiming: (1) to provide a brief overview of thrombolysis in stroke; (2) ...[more]

PMID: 36746381

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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:ImportanceTenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited.ObjectiveTo establish the noninferiority of tenecteplase to alteplase in patients with AIS within 4.5 hours of symptom onset.Design, setting, and participantsThe ORIGINAL study was a multicenter, active-controlled, parallel-group, randomized, open-label, blinded end point, noninferiority trial conducted between July 14, 2021, and July 14, 2023. Participants were recruited from 55 neurology clinics and stroke centers in China and were eligible if they had AIS with a National Institutes of Health Stroke Scale score of 1 to 25 with measurable neurologic deficit and were symptomatic for at least 30 minutes without significant improvement.InterventionsPatients were randomized (1:1) within 4.5 hours of symptom onset to receive intravenous tenecteplase (0.25 mg/kg) or intravenous alteplase (0.9 mg/kg).Main outcomes and measuresThe primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90, tested for noninferiority (risk ratio [RR] margin, 0.937). Safety end points included symptomatic intracerebral hemorrhage (per European Cooperative Acute Stroke Study III definition) and 90-day all-cause mortality.ResultsAmong the 1489 patients randomized, 1465 patients were included in the full analysis set (732 in the tenecteplase group; 733 in the alteplase group) and 446 (30.4%) were female. The primary outcome occurred in 72.7% (532/732) of patients receiving tenecteplase and 70.3% (515/733) receiving alteplase (RR, 1.03 [95% CI, 0.97-1.09]; noninferiority threshold met). Symptomatic intracerebral hemorrhage occurred in 9 patients (1.2%) in each group (RR, 1.01 [95% CI, 0.37-2.70]). The 90-day mortality rate was 4.6% (34/732) in the tenecteplase group and 5.8% (43/736) in the alteplase group (RR, 0.80 [95% CI, 0.51-1.23]).Conclusions and relevanceIn patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile. Findings from this study support tenecteplase as a suitable alternative to alteplase in this setting.Trial registrationClinicalTrials.gov Identifier: NCT04915729.

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Replacing Alteplase with Tenecteplase: Is the Time Ripe?

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Replacing Alteplase with Tenecteplase: Is the Time Ripe?

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