The landscape of stroke treatment is undergoing a significant shift with the introduction of tenecteplase as a viable thrombolytic agent for acute ischemic stroke. Historically, alteplase has been the go-to thrombolytic, but emerging research with a meta-analysis suggests that tenecteplase might be not only noninferior but potentially superior [1]. This has led to its increasing preference in clinical practice.
Evolving Treatment Paradigms
Traditionally, thrombolysis for stroke has been confined to a narrow 4.5-hour window post-onset. This limitation poses a significant challenge given that many patients do not arrive at a hospital in time to benefit from this treatment especially in third-word countries. Additionally, large-vessel occlusions, the most severe subtype of strokes, have poor outcomes even with alteplase treatment. Here, endovascular thrombectomy has shown substantial benefits within a 24-hour window, though accessibility remains a critical issue globally [2].
The TIMELESS Trial
The TIMELESS trial aimed to expand the treatment window for tenecteplase to 24 hours post-stroke onset. It involved patients with large-vessel occlusions and salvageable brain tissue, who were randomly assigned to receive tenecteplase or a placebo. Most of these patients subsequently underwent thrombectomy. The trial found no significant benefit of tenecteplase in this extended window, likely due to the immediate performance of thrombectomy overshadowing any potential benefits of the drug [3].
What is your approach for patients with acute stroke and salvageable brain tissue but outside the 4.5-hour window?
0%Supportive care
0%Thrombectomy
0%Tenecteplase
The TRACE-III Trial
In contrast, the TRACE-III trial, conducted by Xiong et al., focused on a similar patient demographic but excluded those who would undergo immediate thrombectomy. This trial involved 516 Chinese patients and found that tenecteplase significantly improved functional outcomes and recanalization rates compared to standard medical treatment, with no increase in mortality [4].
The TRACE-III trial's design, which prevented immediate thrombectomy, allowed for a more extended exposure to tenecteplase, highlighting its efficacy in a broader treatment window. The findings suggest that tenecteplase can serve as a critical intervention in settings where thrombectomy is not readily available, such as in many developing countries or regions with limited medical infrastructure.
Implications for Global Stroke Care
The results of the TRACE-III trial hold promise for transforming acute stroke care worldwide. In areas lacking thrombectomy facilities, tenecteplase offers a practical alternative that can improve functional outcomes in patients with large-vessel occlusions. This could significantly impact global health, providing a feasible solution for stroke treatment in resource-constrained settings.
Future research should aim to replicate these results in diverse populations and explore the integration of tenecteplase with planned thrombectomy transfers. Despite some limitations, the current evidence positions tenecteplase as a valuable addition to the stroke treatment toolkit, with the potential to enhance patient outcomes significantly.
In summary, tenecteplase's expanded use represents an exciting advancement in stroke care, particularly for patients without immediate access to thrombectomy. Its implementation could bridge a critical gap in stroke treatment, offering hope for better recovery outcomes on a global scale.
References
Burgos AM, Saver JL. Evidence that tenecteplase is noninferior to alteplase for acute ischemic stroke: meta-analysis of 5 randomized trials. Stroke 2019;50:2156-2162.
Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50(12):e344-e418.
Albers GW, Jumaa M, Purdon B, et al. Tenecteplase for stroke at 4.5 to 24 hours with perfusion-imaging selection. N Engl J Med 2024;390:701-711.
Xiong Y, Campbell BCV, Schwamm LH, et al. Tenecteplase for ischemic stroke at 4.5 to 24 hours without thrombectomy. N Engl J Med 2024;391:203-212
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