Ischemic strokes occur when blood flow to the brain is blocked, potentially leading to lasting disabilities. In such cases, doctors can administer specific medications to break down blood clots responsible for the blockage. A recent study suggests that tenecteplase may offer slightly improved functional and disability outcomes compared to alteplase for individuals suffering from acute ischemic strokes. Strokes are a leading cause of death and disability in the United States, with ischemic strokes being the most prevalent type, resulting from interrupted blood flow to the brain.
Healthcare professionals are keen to identify which medications can optimize recovery for those affected by ischemic strokes. A systematic review and meta-analysis published in Neurology, the journal of the American Academy of Neurology, evaluated the efficacy of two clot-dissolving drugs—tenecteplase and alteplase—commonly used to treat ischemic strokes.
The findings indicated that tenecteplase was associated with a greater likelihood of achieving an excellent functional outcome and a reduction in disability three months post-stroke compared to alteplase. These results advocate for the increased adoption of tenecteplase in clinical settings.
Tenecteplase vs. Alteplase: A Comparative Analysis
Addressing blood clots is crucial in the treatment of ischemic strokes. Alteplase must be administered within hours of the onset of stroke symptoms. While the authors of the review acknowledged that “alteplase is the only approved systemic reperfusion treatment for acute ischemic stroke,” they noted that organizations like the European Stroke Organisation have endorsed tenecteplase as an alternative option for treatment.
Researchers aimed to compare the effectiveness of tenecteplase and alteplase when administered within four and a half hours after the onset of stroke symptoms, also examining the safety and efficacy of tenecteplase. The analysis included 11 randomized controlled trials identified through a systematic literature review.
From these trials, researchers analyzed data from 3,788 participants treated with tenecteplase and 3,757 treated with alteplase. The participants exhibited similar baseline characteristics, stroke symptoms, and timing of treatment intervention. The primary outcome measured was excellent functional recovery at three months post-stroke.
Excellent function was defined as a score of 0 to 1 on the modified Rankin Scale, which signifies either no symptoms following the stroke or mild symptoms without significant disability. Additionally, researchers assessed various secondary outcomes, including good functional recovery, which indicates a stroke recovery level ranging from no symptoms to slight disability.
According to their analysis, individuals who received tenecteplase were more likely to achieve an excellent functional outcome than those treated with alteplase. Furthermore, participants treated with tenecteplase exhibited a lower risk of disability three months following the stroke compared to those receiving alteplase.
The rates of good functional outcomes, safety, all-cause mortality, and symptomatic intracranial hemorrhage were comparable between the two treatment groups.
Are There Variants of Tenecteplase?
In a subgroup analysis, the researchers distinguished between two forms of tenecteplase: original and biocopy. Based on data from two studies, the review authors found no significant difference in the rates of excellent functional outcomes between participants receiving biocopy tenecteplase and those receiving alteplase. However, the authors noted that these studies might not possess sufficient statistical power to establish superiority conclusively.
They also performed a trial sequential analysis to confirm tenecteplase’s effectiveness, which indicated that the drug is indeed effective.
José Morales, MD, a vascular neurologist and neurointerventional surgeon at Providence Saint John’s Health Center in Santa Monica, CA, who did not participate in this review, explained that:
“When tenecteplase (TNK) was first released and tested for clinical use in acute stroke, the results were mixed. Some early reports suggested that TNK achieved better recanalization rates, had fewer bleeding complications, and possibly a longer therapeutic window (beyond 4.5 hours). While none of these claims have been validated in randomized trials, there is clear evidence supporting TNK’s non-inferiority regarding safety and efficacy compared to tPA [alteplase]. Meta-analyses like this one are valuable for consolidating data and achieving the necessary sample size to make significant statistical comparisons where individual trials may have fallen short.”
Implications for Stroke Survivors
The findings from this research indicate that tenecteplase may yield slightly better results for individuals experiencing ischemic strokes. Consequently, the authors of the study recommend a shift towards using tenecteplase in clinical practices.
Morales emphasized that: “The ability to administer clot-dissolving medications is crucial for any hospital aiming to assist patients in need. The simplicity of using TNK is supported by solid clinical data, which impacts care systems.”
He added, “Since tPA administration involves an infusion, it has affected the prompt transfer between stroke centers for advanced care. TNK not only simplifies the process but is also backed by growing validated clinical data attesting to its safety and efficacy.”
Christopher Yi, MD, a board-certified vascular surgeon at Memorial Orange Coast Medical Center in Fountain Valley, CA, also not involved in the study, further highlighted the clinical advantages of tenecteplase:
“The clinical implications include a trend toward adopting TNK as the preferred thrombolytic agent for acute ischemic stroke within the early 4.5-hour window. Given its ease of administration, TNK could streamline the thrombolysis process, shorten treatment times, and enable faster transfers between hospitals. Furthermore, the widespread adoption of TNK may enhance patient outcomes and reduce healthcare costs due to its effectiveness.”
However, Yi cautioned that regulatory hurdles, availability, and medicolegal issues must be addressed to ensure effective implementation of this transition. The study’s findings advocate for broader use of TNK, which could lead to adjustments in treatment protocols and guidelines across various healthcare systems.
Is Tenecteplase Approved for Stroke Treatment in the U.S.?
It is essential to acknowledge the limitations of this review. The authors noted that at the time of the meta-analysis, detailed study results from three of the trials had not yet been published.
Additionally, the meta-analysis was conducted at the study level, limiting certain actions such as subgroup analyses and adjustments for confounding variables.
Given the presence of different formulations of tenecteplase in the review, further research may be necessary to investigate the distinctions between original and biocopy tenecteplase.
Researchers were also constrained by the limited number of trials available for analysis, which originated from a select group of countries. Finally, each trial included had its own limitations that could have influenced the outcomes.
The researchers identified specific concerns regarding the trials that might have affected the results, such as certain participants not receiving randomized treatment and one trial lacking guaranteed masking. The trial sequential analyses also made specific assumptions.
Despite these limitations, if subsequent studies continue to affirm tenecteplase’s superiority, its use may become more prevalent in clinical practice.
Alteplase has served as the primary treatment for ischemic stroke for decades and is approved by the Food and Drug Administration (FDA) for this indication. Currently, while tenecteplase is approved for treating heart attacks, it does not yet have FDA approval for stroke treatment, suggesting that future efforts may focus on obtaining this approval.
