Endovascular Intervention Found Effective for "Late Window" Stroke Patients: DAWN Trial Analysis

 

The window for reducing disability and improving functional independence in stroke patients receiving endovascular therapy could extend as far as 24 hours, according to preliminary results from the DAWN trial presented at the European Stroke Organization Conference (ESOC). Assessing late-window and wake-up stroke patients, investigators found that treatment with the Trevo Retriever (Stryker) significantly decreased post-stroke and improved functional independence at 90 days when compared to medical management alone (48.6 percent versus 13.1 percent), a relative reduction in disability of 73 percent. The findings also revealed that one in 2.8 patients treated with the Trevo Retriever within 24 hours of a stroke is saved from severe disability.

            According to co-principal investigator Tudor G. Jovin, MD, Assosciate Professor of Neurology and Neurosurgery at the University of Pittsburgh, these findings suggest the potential for broadening the current guideline of delivering thrombectomy treatment in a less-than-six-hour time window. “We have been using rigid time windows for the selection of patients ever since we started using reperfusion therapy either with endovascular therapy,” said Dr. Jovin in an interview with Practical Neurology®. “This is the first randomized trial that dispels the notion that treatment beyond this window would not be beneficial.”

            Despite the investigators’ conservative estimates when setting out to perform the study, the results suggest a notable magnitude of benefit, according to Dr. Jovin. “The difference between outcome rates in the control group versus the treatment group is the largest of any stroke trials performed to date,” said Dr. Jovin. While the results indicate that patients with large vessel occlusion may benefit from treatment beyond the recommended six-hour window, Dr. Jovin emphasized that the need for timely intervention remains paramount. “The message of this trial is not that we can take our time with these patients,” he said. The sooner the patient is treated, higher is the likelihood that they will have what Dr. Jovin calls mismatch, which is the difference between a brain that is irreversibly damaged and a brain that is threatened to undergo infarction. “The basic pathophysiological principle of reperfusion therapy is that we are trying to treat a patient with as much mismatch as possible.” In most patients, mismatch decreases as time moves on, underscoring the need for timely intervention. However, the DAWN results show that there are patients who still have mismatch beyond the six-hour window who would benefit from intervention, according to Dr. Jovin. “Patients who come to the hospital beyond six hours should not be treated any different than patients who come within six hours and should screened and evaluated appropriately.”

            In terms of next steps, Dr. Jovin believes that the DAWN results pose several important questions for future inquiries, particularly concerning inclusion criteria. Under the study’s strict inclusion criteria, the powerful treatment benefits may suggest that a wider pool of patients may also benefit from this approach. “An important question we’re facing is up to what point on the scale of age and volume of baseline infarct is there benefit? Should we loosen up inclusion criteria and allow larger baseline infarct so we can treat more patients?”

            Beyond the research spectrum, systems of care are gradually evolving to ensure that all patients presenting beyond six-hour window will get screened appropriately and transferred for endovascular treatment if appropriate. This process, according to Dr. Jovin, will not unfold as rapidly as the data, however.  “The whole stroke community was relatively unprepared when five large trials were all published and positive,” he said. “Right now the infrastructure lags behind the data, nevertheless the creation of adequate infrastructure has been identified as a top priority for the field of endovascular treatment of stroke.”

 

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