A stroke survivors chances of living independently after 90 days are not improved by the use of endovascular therapy, according to a study.
Researchers compared the use of endovascular therapy plus the current standard of intravenous tissue plasminogen activator with IV tPA therapy alone.
“This is the largest trial of an intra-arterial intervention for acute ischemic stroke, and is important because it shows that the addition of devices to treat clots within the brain artery was no more effective than treatment with IV tPA alone,” Walter J. Koroshetz, MD, deputy director of the National Institute of Neurological Disorders and Stroke, the National of Institutes of Health branch that funded the study, said in a news release.
“Such devices already are widely used in clinical practice based on dramatic improvements seen in individuals, but without evidence supporting their overall clinical effectivness in a large group.”
Endovascular therapy is known to be associated with significant risk; 16% of the patients in the study had complications from the minimally invasive surgical procedure. The Interventional Management of Stroke, or IMS-III, is described as the only trial designed to assess the overall balance between risk and benefit of intra-arterial treatment in acute stroke patients.
Endovascular therapy involves threading a catheter through an artery in the groin up to the site of a clot in the brain; then administering tPA directly on the clot, which dissolves it or allows it to be removed via coiled wires or a stent system. Based on earlier studies, researchers anticipated that adding endovascular therapy to standard IV tPA would reduce stroke-related disability by providing a means to eliminate very large clots that would otherwise persist despite IV tPA, according to researchers led by Joseph Broderick, MD, of the University of Cincinnati Academic Health Center.
Participants, ages 18 to 82, were enrolled in the study starting in 2006. By April 2012, after 656 of the 900 planned participants had been treated, the studys Data and Safety Monitoring Board said the investigation should be stopped early because 90-day outcomes showed that the benefit was not substantially different between the groups. Patients in the IV tPA alone group (39%) were as likely as those in the combination therapy group (41%) to be functionally independent.
All patients in the study received IV tPA therapy within three hours of their stroke symptoms. Within 40 minutes of that therapy, 434 patients who were randomized to the device-treatment group underwent angiography to identify arterial blockages. Those patients found to have a treatable blockage received endovascular therapy with one of five types of devices. The remaining 222 patients were randomized to receive IV tPA alone.
Endovascular therapy was 40% more effective at removing clots and re-establishing blood flow but did not improve disability due to stroke. “Our study highlights that improved reopening of arteries and delivery of blood flow to the brain is not a guarantee of improved clinical efficacy,” said Broderick, who led a team of researchers from 58 U.S. and international clinical centers.
The time to intra-arterial treatment was 32 minutes longer in IMS III compared with two pilot studies that preceded it. This time span may be an important reason for the lack of clinical benefit despite substantially better revascularization with endovascular therapy as compared to IV tPA, the researchers said. “We probably did not open the arteries quickly enough,” Broderick said.
Cutting the time to endovascular therapy poses significant challenges, given the logistics of assembling the treatment team and room and conducting the procedure, Broderick noted. In addition, most patients do not have immediate access to the level of care required to perform intra-arterial procedures. Instead, they often are treated with IV tPA at a local hospital and transferred to another hospital, all of which further delays the time to treatment.
IMS III sheds light on research gaps that need to be addressed in trials to develop evidence-based recommendations on the use of intra-arterial devices, said Scott Janis, PhD, program director at NINDS.
“These devices still may play a critical role in improving outcomes among people with serious strokes involving clots that cannot be cleared or are cleared very slowly by standard IV tPA,” Janis said.
The study was presented in Honolulu at the American Stroke Associations International Stroke Conference 2013, and also was published in the Feb. 7 issue of the New England Journal of Medicine. The study is available at www.nejm.org/doi/full/10.1056/NEJMoa1214300?query=featured_home#t=articleTop.