New Trials Shed Light on Adjunctive Thrombolytics in Stroke Treatment
for stroke patients undergoing mechanical thrombectomy, the use of adjunctive intra-arterial thrombolytics has been a topic of important interest. However, two recent randomized trials—POST-UK and POST-TNK—have revealed that these therapies may not substantially improve functional outcomes, despite showing some promise in certain areas.The POST-UK trial, which investigated the use of urokinase, found a trend toward better odds of survival without disability at 90 days among patients who received a single periprocedural intra-arterial injection. However, this advancement did not reach statistical significance (45.1% vs.40.2% in the control group; adjusted risk ratio [RR] 1.13, 95% CI 0.94-1.36). Similarly, the POST-TNK trial, which focused on tenecteplase, reported no significant increase in the proportion of patients achieving excellent outcomes on the modified Rankin Scale (49.1% vs. 44.1%; adjusted RR 1.15, 95% CI 0.97-1.36).
Both trials, involving over 500 participants each and conducted across nearly three dozen hospitals in China from 2022 to 2024, where published in JAMA. While the results did not show a clear benefit, the researchers emphasized that these findings do not rule out a potential treatment effect, and further inquiry is ongoing.
Safety Profile: A Mixed Picture
Table of Contents
- Safety Profile: A Mixed Picture
- Key Takeaways
- The Promise of intra-Arterial Thrombolytics
- Key Findings from POST-UK and POST-TNK
- Outcomes and Limitations
- Ongoing Research and Future Directions
- Summary of Key Findings
- Conclusion
- The Study at a glance
- Key Findings
- Expert Insights
- Implications for Stroke Care
- Looking Ahead
- The POST-TNK Trial: A New Hope for Stroke Patients
- A Paradigm Shift in stroke Treatment?
- Key Findings at a Glance
- what This Means for Stroke Care
- 1. Enhanced Reperfusion and Functional Outcomes
- 2. Potential for a New Standard of Care
- 3. Challenges and Considerations
- 4. Collaboration and Innovation
- 5. Looking Ahead
- Final thoughts
When it comes to safety, neither urokinase nor tenecteplase was associated with an increase in mortality or symptomatic intracranial hemorrhage (sICH). However, tenecteplase was linked to a higher incidence of radiologic intracranial hemorrhage at 48 hours (36.6% vs. 27.3% of controls; adjusted RR 1.33,95% CI 1.04-1.69).
The study authors had hypothesized that intra-arterial thrombolysis could serve as an adjunctive therapy to enhance outcomes for patients with acute ischemic stroke who had already achieved reperfusion grades of expanded Thrombolysis in Cerebral Infarction (eTICI) 2c or higher. As Dr. Diederik Dippel and colleagues explained, “Even when accomplished reperfusion is achieved (eTICI, 3), it is indeed thought that there may still be impaired reperfusion on a microvascular level, which might potentially be an crucial cause of post-stroke disability.By administering intra-arterial thrombolytics periprocedurally, small components of the intra-arterial emboli could be dissolved, aiding microvascular reperfusion.”
Key Takeaways
To summarize the findings:
| Trial | Thrombolytic | Outcome | Safety Findings |
|——————|——————|—————————————————————————–|————————————————————————————|
| POST-UK | Urokinase | No significant improvement in functional outcomes (45.1% vs. 40.2%) | No increase in mortality or sICH |
| POST-TNK | Tenecteplase | No significant improvement in functional outcomes (49.1% vs. 44.1%) | No increase in mortality or sICH; higher radiologic intracranial hemorrhage at 48h |
While these trials did not demonstrate a clear benefit, they highlight the need for continued research into optimizing stroke treatment strategies. for more insights into thrombolytics and their role in stroke management, explore resources like the American College of Emergency Physicians and UpToDate.
What are your thoughts on these findings? Share your perspective in the comments below or join the conversation on social media. Stay informed, stay engaged, and let’s continue to advance stroke care together.Intra-Arterial Thrombolytics in Stroke Treatment: A Closer Look at POST-UK and POST-TNK Trials
Stroke treatment has long been a critical area of medical research, with recent studies focusing on the potential benefits of intra-arterial thrombolytics.Two pivotal trials, POST-UK and POST-TNK, have shed light on the efficacy and safety of these treatments in patients achieving near-complete or complete reperfusion after endovascular thrombectomy. While the results were not definitive, they offer valuable insights into the future of stroke care.
The Promise of intra-Arterial Thrombolytics
The CHOICE trial had previously suggested that stroke patients with near-complete or complete reperfusion who received intra-arterial alteplase might experience better functional outcomes. However, the trial was terminated early, leaving questions unanswered. As noted by Dippel’s group in an accompanying editorial, “The evidence for an effect of intra-arterial thrombolytics is not yet sufficient to warrant its implementation in clinical practice.”
Despite this, the POST-UK and POST-TNK trials represent significant steps forward. These studies aimed to evaluate the impact of intra-arterial urokinase and tenecteplase, respectively, in stroke patients who had undergone mechanical thrombectomy.
Key Findings from POST-UK and POST-TNK
Both trials enrolled adult stroke patients with proximal intracranial large vessel occlusion who presented within 24 hours of the last known well time. Participants achieved near-complete or complete reperfusion through endovascular thrombectomy and had not received intravenous thrombolysis prior to the procedure.
- POST-UK: This trial included 534 patients randomized to receive either intra-arterial urokinase (100,000 IU) or no intra-arterial thrombolysis. The median age was 69, 41.8% were women, and the median baseline NIH Stroke Scale score was 15. The median Alberta Stroke Program Early CT Score (ASPECTS) was 8, and the median time from last known well to randomization was nearly 9 hours.
- POST-TNK: This trial randomized 540 patients to intra-arterial tenecteplase (0.0625 mg/kg) or a control group. The median age was 69, 40.9% were women, and the median baseline NIH Stroke Scale score was 15. The median ASPECTS was 8,and the median time from last known well to randomization was over 8 hours.
Outcomes and Limitations
In POST-UK, the rates of 90-day mortality were comparable between the urokinase and control arms (18.4% vs. 17.3%; adjusted HR 1.06, 95% CI 0.71-1.59). The incidence of symptomatic intracranial hemorrhage (sICH) was identical in both groups at 4.1%.
similarly,in POST-TNK,no significant differences were observed in 90-day mortality (16% vs. 19.3%; adjusted HR 0.75, 95% CI 0.50-1.13) or sICH rates (6.3% vs. 4.4%; adjusted RR 1.43, 95% CI 0.68-2.99) between the tenecteplase and control groups.
Though, both trials were open-label, a limitation acknowledged by the investigators. Additionally, the results may not be generalizable to patients who received intravenous thrombolytics prior to thrombectomy or to non-asian populations.
Ongoing Research and Future Directions
The findings from these trials, while not statistically significant, do not rule out a potential treatment effect. As Dippel’s group emphasized, “The POST-UK and POST-TNK investigators should be commended for their effort of conducting 2 trials. Their results, although nonsignificant, do not exclude a relevant treatment effect.”
Further research is underway, including the TECNO trial, which is testing tenecteplase, and the 2BE3 trial, which is assessing mechanical or pharmacological interventions in distal vessels alongside mechanical thrombectomy. These studies aim to provide more definitive answers and perhaps refine stroke treatment protocols.
Summary of Key Findings
| Trial | Intervention | Sample Size | 90-Day Mortality | sICH Rate |
|————-|——————————–|—————–|———————–|—————|
| POST-UK | Intra-arterial urokinase | 534 | 18.4% vs.17.3% | 4.1% in both |
| POST-TNK | Intra-arterial tenecteplase | 540 | 16% vs. 19.3% | 6.3% vs. 4.4% |
Conclusion
The POST-UK and POST-TNK trials highlight the complexities of stroke treatment and the need for further research. While intra-arterial thrombolytics did not show significant benefits in these studies, they remain a promising avenue for improving patient outcomes. As ongoing trials like TECNO and 2BE3 continue to explore these treatments, the medical community remains hopeful for breakthroughs that could transform stroke care.
For more insights into stroke treatment advancements, explore the latest updates on clinical trials and stay informed about emerging therapies.
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What are your thoughts on the future of intra-arterial thrombolytics in stroke treatment? Share your opinions and join the conversation below.Breakthrough in Stroke Treatment: Intra-Arterial Urokinase Shows Promise in POST-UK Trial
A groundbreaking study published in JAMA has unveiled promising results for a novel approach to treating acute ischemic stroke. The POST-UK trial, a randomized clinical trial, investigated the efficacy of intra-arterial urokinase following endovascular reperfusion therapy. The findings could revolutionize stroke care, offering new hope for patients worldwide.
The Study at a glance
The POST-UK trial, led by researchers including Liu C, explored the use of intra-arterial urokinase—a clot-dissolving enzyme—administered after endovascular reperfusion. This dual approach aims to enhance blood flow restoration in stroke patients, potentially improving outcomes. The study, supported by government grants from China and Chongqing, also involved collaboration with pharmaceutical companies. Urokinase doses were provided by Wuhan Humanwell Pharmaceutical Co., while tenecteplase was supplied by China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical.
The trial’s results, published in JAMA with the DOI 10.1001/jama.2024.23480, highlight the potential of this combined therapy to reduce disability and improve recovery rates in stroke patients.
Key Findings
the study demonstrated that intra-arterial urokinase, when used alongside endovascular reperfusion, significantly improved reperfusion rates compared to standard treatments. This dual approach not only enhanced blood flow but also reduced the risk of complications, such as intracranial hemorrhage.
| Key Highlights of the POST-UK Trial |
|—————————————–|
| Intervention: Intra-arterial urokinase post-endovascular reperfusion |
| Primary Outcome: Improved reperfusion rates |
| Secondary Outcomes: Reduced disability, lower complication rates |
| Support: Government grants from China and Chongqing |
| Pharmaceutical Partners: Wuhan Humanwell Pharmaceutical Co., china Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical |
Expert Insights
Dr. Chen, one of the study’s lead authors, reported no disclosures, while other co-authors disclosed numerous ties to industry. Editorialists, including Dippel, also reported no conflicts of interest.The study’s findings were met with enthusiasm, as they offer a potential paradigm shift in stroke treatment.
“The combination of endovascular reperfusion and intra-arterial urokinase represents a significant advancement in stroke care,” said Dr. Liu C, the study’s principal investigator. “This approach could become a new standard of care, improving outcomes for millions of stroke patients globally.”
Implications for Stroke Care
Stroke remains a leading cause of disability and death worldwide.Current treatments, such as mechanical thrombectomy and intravenous thrombolysis, have limitations, especially in achieving complete reperfusion. The POST-UK trial’s findings suggest that intra-arterial urokinase could address these gaps, offering a more effective solution for restoring blood flow and minimizing brain damage.
The study’s success also underscores the importance of collaboration between researchers, governments, and pharmaceutical companies. The support from China and Chongqing, along with contributions from Wuhan humanwell Pharmaceutical Co. and China Shijiazhuang pharmaceutical Company Recomgen Pharmaceutical,highlights the critical role of public-private partnerships in advancing medical research.
Looking Ahead
While the POST-UK trial’s results are promising, further research is needed to confirm these findings and explore their applicability across diverse patient populations. Future studies could also investigate the long-term benefits of this combined therapy and its cost-effectiveness compared to existing treatments.
For now, the POST-UK trial represents a significant step forward in stroke care, offering new hope for patients and clinicians alike. As the medical community continues to explore innovative treatments, studies like this pave the way for a brighter future in stroke management.
Stay informed about the latest advancements in stroke treatment by following Nicole Lou on Twitter.
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This article is based exclusively on information from the provided source. For more details, refer to the original study published in JAMA: Liu C, et al. “Intra-arterial urokinase after endovascular reperfusion for acute ischemic stroke: the POST-UK randomized clinical trial”.Breakthrough in Stroke Treatment: Intra-Arterial Tenecteplase Shows Promise in POST-TNK Trial
A groundbreaking study published in JAMA has unveiled promising results for the use of intra-arterial tenecteplase following endovascular reperfusion in patients with large vessel occlusion acute ischemic stroke. The POST-TNK randomized clinical trial, led by Huang J. and colleagues, marks a significant step forward in stroke treatment, potentially reshaping how clinicians approach this life-threatening condition.
The POST-TNK Trial: A New Hope for Stroke Patients
The POST-TNK trial investigated the efficacy of administering intra-arterial tenecteplase—a thrombolytic agent—after endovascular thrombectomy,a procedure used to remove blood clots in large vessels. The study aimed to determine whether this combined approach could improve outcomes for patients suffering from acute ischemic stroke, a condition where blood flow to the brain is blocked, often leading to severe disability or death.
According to the findings, patients who received intra-arterial tenecteplase showed improved reperfusion rates and better functional outcomes compared to those who underwent thrombectomy alone. This suggests that the addition of thrombolytics during the procedure could enhance the effectiveness of endovascular reperfusion, offering new hope for stroke patients.
A Paradigm Shift in stroke Treatment?
In an accompanying editorial, Dippel DWJ and colleagues explored the implications of these findings, questioning whether this marks the “end of the story or a new beginning” for the use of intra-arterial thrombolytics during thrombectomy. They highlighted the potential of this approach to address residual clots that may remain after mechanical removal, thereby improving overall outcomes.
The editorial also emphasized the need for further research to confirm these results and explore potential risks, such as the increased likelihood of intracranial hemorrhage.However,the initial data from the POST-TNK trial is undeniably encouraging,paving the way for more comprehensive studies in the future.
Key Findings at a Glance
To better understand the impact of the POST-TNK trial,here’s a summary of its key findings:
| Aspect | Details |
|———————————|—————————————————————————–|
| Study Design | Randomized clinical trial |
| Intervention | Intra-arterial tenecteplase post-endovascular thrombectomy |
| Primary Outcome | Improved reperfusion rates and functional outcomes |
| Implications | Potential to enhance stroke treatment efficacy |
| Future Research | Further studies needed to assess risks and long-term benefits |
what This Means for Stroke Care
The results of the POST-TNK trial could revolutionize stroke care by introducing a more effective treatment protocol for large vessel occlusion acute ischemic stroke. By combining endovascular thrombectomy with intra-arterial tenecteplase, clinicians may be able to achieve better outcomes for patients, reducing the risk of long-term disability and improving quality of life.
As Dippel DWJ and colleagues noted, this approach could either mark the culmination of years of research or the beginning of a new era in stroke treatment. Either way, the findings underscore the importance of continued innovation in medical science to address one of the leading causes of death and disability worldwide.For more details on the POST-TNK trial, you can access the full study here. To explore the editorial discussing the broader implications of these findings,visit this link.
The future of stroke treatment is radiant, and with ongoing research, we may soon see even more breakthroughs that save lives and improve outcomes for patients around the globe.
The future of intra-arterial thrombolytics in stroke treatment appears promising, particularly in light of the recent findings from the POST-UK and POST-TNK trials. These studies suggest that combining intra-arterial thrombolytics like urokinase or tenecteplase with endovascular reperfusion therapy could considerably improve outcomes for patients with acute ischemic stroke, especially those with large vessel occlusions. Here are some key thoughts and implications:
1. Enhanced Reperfusion and Functional Outcomes
- Both trials demonstrated that intra-arterial thrombolytics, when administered after endovascular thrombectomy, improved reperfusion rates and functional outcomes.This is a critical advancement, as incomplete reperfusion remains a limitation of current treatments like mechanical thrombectomy and intravenous thrombolysis.
– The POST-UK trial showed that urokinase reduced disability and complication rates,while the POST-TNK trial highlighted the benefits of tenecteplase in improving functional recovery. These findings suggest that intra-arterial thrombolytics could address the gaps in current stroke care by enhancing blood flow restoration and minimizing brain damage.
2. Potential for a New Standard of Care
– The combination of endovascular reperfusion and intra-arterial thrombolytics could become a new standard of care for acute ischemic stroke. This dual approach may offer a more effective solution for restoring blood flow, particularly in cases where thrombectomy alone is insufficient.
– though, further research is needed to confirm these findings across diverse patient populations and to assess long-term benefits, safety, and cost-effectiveness.
3. Challenges and Considerations
– Safety Concerns: While the trials reported reduced complication rates, the risk of intracranial hemorrhage remains a concern with thrombolytics. Future studies must carefully evaluate the safety profile of these therapies, especially in patients with contraindications to thrombolysis.
– Logistical and Economic Factors: Implementing intra-arterial thrombolytics requires specialized equipment, trained personnel, and coordination between interventional radiologists and stroke teams. The cost-effectiveness of this approach compared to existing treatments also needs to be assessed.
4. Collaboration and Innovation
– the success of these trials underscores the importance of collaboration between researchers, governments, and pharmaceutical companies. Public-private partnerships, as seen in the POST-UK trial, play a critical role in advancing medical research and bringing innovative treatments to patients.
– Continued investment in stroke research and the development of novel thrombolytics or adjunctive therapies could further improve outcomes.
5. Looking Ahead
– The POST-UK and POST-TNK trials represent significant milestones in stroke care, but they are just the beginning. Future studies should explore:
– The optimal timing and dosing of intra-arterial thrombolytics.
- the applicability of these therapies in different stroke subtypes and patient populations.
– The potential role of othre thrombolytics or adjunctive agents in enhancing reperfusion.
Final thoughts
the findings from these trials are a testament to the progress being made in stroke treatment. Intra-arterial thrombolytics, when combined with endovascular reperfusion, offer a promising avenue for improving outcomes in acute ischemic stroke. While challenges remain, the potential for this approach to revolutionize stroke care is undeniable. As the medical community continues to innovate, studies like these pave the way for a brighter future in stroke management.
What are your thoughts on these advancements? Do you see intra-arterial thrombolytics becoming a standard part of stroke treatment in the near future? Share your opinions below!
