IMS 3 Substudy Shows Delays in Stroke Treatment Lead to Worse Outcomes

February 8, 2013—According to a study presented at the American Stroke Association's International Stroke Conference 2013 in Honolulu, Hawaii, every 30-minute delay in breaking up a blood clot from a stroke was associated with a 10% decrease in the probability of a good outcome, regardless of other factors such as stroke severity. 

The importance of timing using endovascular therapy has not been as well studied, commented study investigator Pooja Khatri, MD, in the ASA announcement. Dr. Khatri is Director of Acute Stroke and Associate Professor of Neurology at the University of Cincinnati in Ohio. The study was funded by the National Institutes of Neurological Disorders and Stroke.

As summarized in the ASA press release, the study was a subset of patients from the Interventional Stroke Management III trial (IMS 3), which included patients who received both intravenous tissue plasminogen activator (tPA) and endovascular therapy, and had blood flow restored within 7 hours of stroke onset.

The IMS 3 trial compared intravenous tPA alone and with added endovascular therapy, but neither proved superior. ASA noted that tPA must be administered within 4.5 hours of symptom onset. Faster start of treatment leads to better recovery, whereas endovascular therapy is usually used after the 4.5-hour time window for intravenous tPA has closed, or for larger or more difficult clots that do not dissolve with other treatments.

IMS 3 was a multicenter international trial in which about 900 participants with ischemic stroke were to be randomly assigned to receive tPA alone or tPA plus endovascular therapy. All patients received tPA within 3 hours of stroke onset. The trial was stopped in April 2012, with about two-thirds of intended patients enrolled, after an interim analysis determined the additional therapy was highly unlikely to benefit patients.

According to the ASA, the substudy investigators examined data on 240 patients who received both intravenous and endovascular therapy in IMS 3 who had major clots in brain arteries. Among these patients, blood flow was restored in 182 patients within seven hours from stroke onset. Patients were evaluated for level of disability 90 days after treatment. Time proved critical regardless of other factors, such as absence of a disability prior to stroke, stroke severity, or the results of the patients' scans before treatment.

“We have effective endovascular treatments for unblocking arteries, but as far as actually making stroke patients clinically better, we need to move a lot faster,” commented Dr. Khatri in the ASA press release. “There's a window of time that we have during a stroke and if we pass that point, it's the point of no return in terms of brain damage. For endovascular therapy to work we may need to deliver it more quickly, and that is what future trials need to test. If we had opened arteries faster in the IMS 3 trial, we might have had a positive trial that brought a more effective treatment to patients with severe strokes.”

Dr. Khatri advised that delays include patients not recognizing the signs of a stroke, family members driving patients to the hospital instead of calling emergency services, emergency departments being too slow in identifying or evaluating a stroke for treatment, and delays in transferring patients to a hospital or facility with expertise in endovascular therapy.

“In the future, we may also be able to use MRI and CT scans to take images of a patient's brain to identify whose treatment window is closing, those who have a little more time, or those with the types of clots most likely to benefit from endovascular therapy,” said Dr. Khatri. “These approaches are under investigation. But, even for those with favorable scans, we can't get away from the fact that the clock is ticking and an acute stroke patient needs to be managed with the highest level of urgency.”