A recent study to find which medications work best in improving overall outcomes for ischaemic stroke patients saw European researchers comparing the effectiveness of two clot-dissolving drugs.
Their systematic review and meta-analysis found that tenecteplase had a higher association with excellent functional outcome and decreased disability three months after a stroke than alteplase.
The results of their review support increasing the use of tenecteplase in clinical practice, they noted in their findings, published in Neurology.
Tenecteplase vs alteplase
Taking action to dissolve clots can be part of ischaemic stroke treatment, and alteplase has to be administered within hours of stroke symptoms starting.
The review authors noted that “alteplase is the only approved systemic reperfusion treatment of acute ischaemic stroke”, but they also noted that some groups, like the European Stroke Organisation, recommend using tenecteplase as an alternative treatment.
The researchers sought to compare the use of tenecteplase and alteplase within four and a half hours of stroke symptom onset. They also examined tenecteplase’s efficacy and safety.
Medical News Today reports that their review and meta-analysis included 11 randomised controlled trials, identified through a systematic literature search.
From all of the trials, they were able to examine data from 3 788 participants who received tenecteplase, and 3 757 participants who received alteplase. All had similar baseline characteristics, stroke symptoms, and time of treatment intervention.
The main outcome sought was excellent function outcome at three months after a stroke occurred.
Excellent function was described as a score of zero to one on the modified Rankin Scale, which corresponds to either no symptoms post-stroke or some symptoms but no significant disability.
The team also looked at several secondary outcomes, like good functional outcome, which indicates a stroke recovery level range of no symptoms to slight disability.
Based on their analyses, participants who received tenecteplase were more likely to experience an excellent functional outcome compared with those who received alteplase.
Tenecteplase-treated participants also had a lower risk for disability three months post-stroke compared with alteplase-treated participants.
Researchers observed similar rates of good functional outcome, safety, all-cause mortality, and symptomatic intracranial haemorrhage between the treatment groups.
Different types of tenecteplase
In a subgroup analysis, the researchers distinguished between two types of tenecteplase: original and biocopy.
Based on the findings from two studies, the review authors did not find a significant difference in excellent functional outcome rates in participants who received biocopy tenecteplase and participants who received alteplase.
However, the authors noted that the two studies possibly “do not have enough statistical power to demonstrate superiority”.
They further conducted a trial sequential analysis to see if they could firmly conclude teneteplase’s effectiveness. This analysis suggested that tenecteplase is effective.
José Morales, MD, a vascular neurologist and neurointerventional surgeon at Providence Saint John’s Health Centre in Santa Monica, California, who was not involved in this review, said:
“When tenecteplase (TNK) was first released and trialled for clinical use in acute stroke, there were mixed signals. Some initial reports indicated TNK achieved better recanalisation rates, had less bleeding complications, and possibly could provide a longer therapeutic window ([over] 4.5 hours).
“None of these has been borne out in randomised trials, but there was a clear signal of TNK’s non-inferiority both in terms of safety and efficacy compared with tPA [alteplase]. Meta analyses such as these are helpful to consolidate data and achieve the sample size necessary to draw meaningful statistical comparisons where individual trials might have fallen short.”
Implications for stroke patients
This research suggests that tenecteplase may lead to slightly better outcomes for people who experience ischaemic stroke. Thus, the study authors advocate for transitioning to tenecteplase in clinical practice.
Christopher Yi, MD, a board-certified vascular surgeon at Memorial Orange Coast Medical Centre in California, also not involved in the study, added to the clinical benefits of using tenecteplase:
“These include a shift in standard practice towards using TNK as the preferred thrombolytic agent for AIS (acute ischaemic stroke) within the early 4.5-hour window. Given its ease of administration, TNK could streamline the thrombolysis process, reduce treatment times, and facilitate faster transfers between hospitals. Additionally, adopting TNK widely may improve patient outcomes and reduce healthcare costs due to its effectiveness.
“However,” Yi cautioned, “challenges such as regulatory barriers, availability, and medicolegal considerations must be addressed to implement this transition effectively. The findings advocate for TNK’s broader implementation, potentially leading to modifications in treatment protocols and guidelines across various healthcare systems.”
Is tenecteplase approved for stroke treatment in the US?
The review has limitations, said its authors, who pointed out that at the time they conducted the meta-analysis, three of the trials had not had detailed study results published.
Second, the meta-analysis was a study-level analysis, which does not allow for certain actions like subgroup analyses and confounding adjustments.
There were also different types of tenecteplase under review, so more research may be required to examine the difference between original tenecteplase and biocopy tenecteplase.
Researchers were also limited by trials available for analysis, which came from a limited number of countries. Finally, all included trials had their own limitations that could have affected any of the results of the analysed trials.
The researchers were able to identify certain concerns of the trials that could have affected the results, such as certain participants not receiving randomised treatment and one trial where they could not guarantee masking. The trial sequential analyses also made certain assumptions.
Despite these limitations, if future research continues to confirm tenecteplase’s superiority, it may become more widely used in clinical practice.
Alteplase has been a first-line treatment for ischaemic stroke for decades and has approval from the US Food and Drug Administration (FDA) for this purpose.
Currently, tenecteplase, while approved as a treatment for heart attacks, does not have FDA approval for this purpose, so future action may involve seeking this approval.
Study details
Tenecteplase vs Alteplase in acute ischaemic stroke within 4.5 hours: a systematic review and meta-analysis of randomised trials
Published in Neurology on 16 October 2024
Lina Palaiodimou, Aristeidis Katsanos, Guillaume Turc et al.
Abstract
Background and Objectives
The current European Stroke Organisation expedited recommendation on tenecteplase (TNK) for acute ischemic stroke (AIS) advocates that TNK 0.25 mg/kg can be used alternatively to alteplase (tissue plasminogen activator [TPA]) for AIS of <4.5 hours’ duration, based on a meta-analytical approach establishing non-inferiority. Since the publication of these guidelines, 4 additional randomized controlled clinical trials (RCTs) have provided further insight.
Methods
We conducted an updated systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of TNK 0.25 mg/kg compared with TPA for the treatment of AIS within 4.5 hours of onset. The primary outcome was defined as the excellent functional outcome at 3 months (modified Rankin Scale [mRS] score 0–1), whereas good functional outcome (mRS score 0–2), reduced disability at 3 months (≥1-point reduction across all mRS scores), symptomatic intracranial haemorrhage (sICH), and 3-month mortality were evaluated as secondary outcomes. Pooled estimates were calculated with random-effects model. A prespecified subgroup analysis was performed stratifying for TNK formulation, that is, original TNK vs biocopy: recombinant human TNK tissue-type plasminogen activator that is available in China and has a different production process.
Results
Eleven RCTs were included comprising a total of 3,788 patients treated with TNK vs 3,757 patients treated with TPA. TNK was associated with higher likelihood of excellent functional outcome (risk ratio [RR] 1.05, 95% CI 1.01–1.10; p = 0.012; I2 = 0%; risk difference 2.95%; 95% CI 0.76%–5.14%; p = 0.008; I2 = 0%) and reduced disability at 3 months (common odds ratio 1.10, 95% CI 1.01–1.19; p = 0.034; I2 = 0%) compared with TPA while good functional outcome (RR 1.03, 95% CI 0.99–1.07; p = 0.142; I2 = 28%) was similar between the groups. Regarding safety outcomes, similar rates of sICH (RR 1.12, 95% CI 0.83–1.53; p = 0.456; I2 = 0%) and 3-month mortality (RR 0.97, 95% CI 0.82–1.15; p = 0.727; I2 = 12%) were observed. When stratified for TNK regimen (original vs biocopy), statistical significance in achieving an excellent functional outcome at 3 months was retained for the original TNK (RR 1.05, 95% CI 1.00–1.10; p = 0.044; I2 = 0%).
Discussion
The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice.
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