Benefit of Late Thrombolysis in Large Vessel Strokes

Core Concepts

Thrombolysis beyond 4.5 hours may benefit specific patient groups with large vessel strokes, as indicated by the TIMELESS trial.

Abstract

The TIMELESS trial analyzed the efficacy of thrombolysis in large vessel occlusion strokes beyond the traditional 4.5-hour window. Key findings include:

• Initial trial results did not show significant improvement in primary endpoints.
• Subgroup analyses revealed potential benefits for patients with M1 occlusions and those receiving tenecteplase before thrombectomy.
• Safety of thrombolysis up to 24 hours was established, but overall population did not show significant benefits.
• Patients treated at the time of thrombectomy also showed improvement.
• M1 occlusions demonstrated a compelling treatment effect with tenecteplase.
• Further analysis is needed to understand the lack of benefit in M2 occlusions.
• The study suggests that thrombolysis may not help patients with large vessel occlusions who do not undergo thrombectomy.

Stats

"The primary endpoint showed a shift in the Rankin disability score toward less disability in the tenecteplase group with a common odds ratio of 1.59 (95% CI, 1.00-2.52)."
"The secondary outcome was the percentage of patients who were functionally independent (mRS 0-2), and there was a substantial 15% increase in that outcome with tenecteplase in the patients with an M1 occlusion, Albers reported."

Quotes

"For years, it has been thought too dangerous to give stroke patients thrombolysis after 4.5 hours, but now we know if we choose the patients appropriately with imaging-based selection, we have a group that we are not going to harm with thrombolysis." - Gregory Albers
"The trial results tentatively suggest that pretreatment with tenecteplase before thrombectomy may be beneficial in patients with occlusions in the M1 segment when administered in the 4.5- to 24-hour window." - Dana Leifer

Key Insights Distilled From

Benefit of Late Thrombolysis in Large Vessel Strokes?

by at www.medscape.com 02-19-2024

https://www.medscape.com/viewarticle/benefit-late-thrombolysis-large-vessel-strokes-2024a10003bl

Deeper Inquiries

How can the findings of the TIMELESS trial impact current guidelines for thrombolysis in stroke patients

The findings of the TIMELESS trial have the potential to significantly impact current guidelines for thrombolysis in stroke patients. Traditionally, thrombolysis has been limited to a 4.5-hour time window due to concerns about safety and efficacy. However, the TIMELESS trial suggests that selected patients with large vessel occlusion strokes may still benefit from thrombolysis even beyond this time window. Specifically, patients with M1 occlusions showed a compelling treatment effect with thrombolysis, leading to a shift in disability scores and an increase in functional independence. These results challenge the existing guidelines and indicate that with appropriate patient selection based on imaging, thrombolysis can be safely administered up to 24 hours post-stroke onset.

What challenges might arise in implementing thrombolysis beyond the traditional time window in clinical practice

Implementing thrombolysis beyond the traditional time window in clinical practice may pose several challenges. One of the primary challenges is the need for accurate and timely imaging to identify patients with salvageable brain tissue who could benefit from late thrombolysis. This requires access to advanced imaging techniques and expertise, which may not be readily available in all healthcare settings. Additionally, there may be concerns about the increased risk of complications associated with thrombolysis in patients presenting later, as the potential benefits must outweigh the risks. Moreover, logistical challenges such as coordinating transfer to comprehensive stroke centers for thrombectomy after thrombolysis at primary stroke centers can introduce delays in treatment, impacting the overall effectiveness of the intervention.

How can the study's results influence future research on thrombolysis efficacy in different occlusion types

The results of the TIMELESS trial can significantly influence future research on thrombolysis efficacy in different occlusion types. The unexpected findings that M1 occlusions showed a benefit from thrombolysis while M2 occlusions did not raise questions about the optimal patient selection criteria for late thrombolysis. Further research is needed to understand the underlying mechanisms that drive the differential response to thrombolysis based on occlusion location. Additionally, exploring vessel recanalization rates in patients undergoing angiography can provide insights into the effectiveness of thrombolysis in different occlusion types. Future studies should focus on refining patient selection criteria, optimizing treatment protocols, and investigating the impact of thrombolysis on vessel recanalization to improve outcomes in stroke patients with large vessel occlusions.