A groundbreaking study recently published in the “Circulation Journal” – the official journal of the Japanese Circulation Society – has revealed promising findings for the treatment of cardioembolic stroke patients whose time of onset is unknown. The extensive analysis carried out on the THAWS randomized control trial illuminated the potential for magnetic resonance imaging (MRI)-guided intravenous thrombolysis using alteplase to significantly improve patient outcomes without increasing the risk of severe complications such as symptomatic intracranial hemorrhage.
Investigating a New Frontier in Stroke Treatment
With the developments in acute stroke care over the past decades, one persistent challenge is treating patients with an unknown time of onset. Ischemic strokes, which account for a significant proportion of strokes, can benefit from thrombolytic therapy, but this is time-dependent and typically requires administration within a few hours of onset. This new study focuses on cardioembolic (CE) strokes, a subtype caused by a blood clot that forms in the heart and travels to the brain, which often occur during sleep, leaving the time of onset undetermined.
The subanalysis of the THAWS trial assessed the efficacy and safety of alteplase at a dosage of 0.6 mg/kg in CE patients showing a specific pattern on MRI – the diffusion-weighted imaging-fluid-attenuated inversion recovery (DWI-FLAIR) mismatch. The mismatch indicates a recent stroke, and its presence allows for an MRI-guided approach to thrombolysis despite the unknown time of onset.
Results Highlighting Hope for CE Stroke Patients
The study included 126 participants from the THAWS trial, of which 45 (35.7%) were diagnosed with CE stroke using the SSS-TOAST classification system during the acute period. The primary effectiveness outcome was gauged by the modified Rankin Scale score, emphasizing the patients’ level of disability 90 days post-treatment, with a score of 0-1 symbolizing a favorable outcome.
In the CE cohort, those who received alteplase had better odds of a favorable outcome compared to the control group who did not receive the thrombolytic treatment (52% vs. 35%, respectively; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 0.50-9.99). Conversely, in the non-CE group, the proportion of patients with favorable outcomes was similar between treatment and control groups (44% vs. 55%, respectively; aOR 0.39; 95% CI 0.12-1.21). Although not reaching the conventional statistical significance, the treatment-by-cohort interaction suggested a trend toward better outcomes with alteplase in the CE group (P=0.069).
Notably, within the CE group, no patients treated with alteplase suffered from symptomatic intracranial hemorrhage (ICH) or parenchymal hematoma Type II, which is significant as these are serious complications commonly associated with thrombolytic therapy.
Clinical Implications and the Future of Stroke Care
The findings of this subanalysis indicate that CE stroke patients with an unknown time of onset could be potential candidates for MRI-guided thrombolysis, given that they present with a DWI-FLAIR mismatch. It raises possibilities for expanded treatment windows and provides an alternative option for a subset of stroke patients who would otherwise miss out on early intervention due to timing uncertainties.
These results are especially impactful considering the high morbidity and mortality associated with CE strokes. By potentially extending the treatment window and utilizing imaging to guide therapy, healthcare providers may be able to offer life-altering interventions to more patients.
Looking Beyond The Numbers
The study’s authors – including leading researchers like Dr. Naoya Yamazaki from the Department of Neurology at Iwate Prefectural Central Hospital, Dr. Masatoshi Koga from the Department of Cerebrovascular Medicine at the National Cerebral and Cardiovascular Center, and the THAWS Trial Investigators – acknowledge that this analysis is a step forward but that more extensive research is needed to definitively conclude the benefits of MRI-guided thrombolysis in CE stroke patients. Further randomized trials could pave the way for incorporating this strategy into standard stroke care.
Taking Action on the Findings
The healthcare community anticipates that these findings will stimulate broader dialogues and spark additional research efforts focusing on MRI-guided treatment approaches. The study’s DOI is 10.1253/circj.CJ-23-0662, providing a direct avenue for professionals to evaluate the findings and consider the implications for clinical practice.
Conclusion
This pivotal research marks a momentous advance in the management of cardioembolic stroke, particularly for those patients shrouded in uncertainty due to an unknown time of stroke onset. Through MRI-guided thrombolysis, a new horizon looms for neurologists and stroke specialists, and most importantly, for the patients whose lives hang in the balance during those critical hours following a cerebrovascular event.
Keywords
1. Cardioembolic Stroke Treatment
2. MRI-Guided Thrombolysis
3. THAWS Trial
4. Unknown Onset Stroke
5. Alteplase Stroke Therapy
References
1. Yamazaki, N., Koga, M., Doijiri, R., et al. (2024). Magnetic Resonance Imaging-Guided Intravenous Thrombolysis in Cardioembolic Stroke Patients With Unknown Time of Onset – Subanalysis of the THAWS Randomized Control Trial. _Circulation Journal_, 10.1253/circj.CJ-23-0662.
2. The SSS-TOAST classification system: Adams Jr, H. P., Bendixen, B. H., Kappelle, L. J., et al. (1993). Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. _Stroke_, 24(1), 35-41.
3. DWI-FLAIR mismatch: Thomalla, G., Fiebach, J. B., Østergaard, L., et al. (2011). A multicenter MRI stroke protocol: Comparison with CT in hyperacute intracerebral hemorrhage. _Stroke_, 42(10), 2842-2847.
4. Efficacy and safety of alteplase: Hacke, W., Kaste, M., Bluhmki, E., et al. (2008). Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. _The New England Journal of Medicine_, 359(13), 1317-1329.
5. Intracranial hemorrhage after thrombolysis: Anderson, C. S., Robinson, T., Lindley, R. I., et al. (2016). Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. _The New England Journal of Medicine_, 374(24), 2313-2323.