HONOLULU—Functional and safety outcomes were not significantly different between patients with acute ischemic stroke treated with IV t-PA and those treated with IV t-PA and endovascular therapy, said investigators at the 2013 International Stroke Conference.
In the Interventional Management of Stroke (IMS) III study, 40.8% of patients randomized to receive endovascular therapy plus IV t-PA had a modified Rankin Scale (mRS) score of 2 or lower at 90 days, compared with 38.7% of patients who received IV t-PA alone, said Joseph Broderick, MD, Chair of the Department of Neurology at the University of Cincinnati and lead investigator of IMS III. The difference between the groups was not statistically significant. Mortality and other safety outcomes also were not significantly different between the two groups of patients in the study, which was halted early because of futility after 656 of the planned 900 patients had been randomized. The study was published online ahead of print on February 7 in the New England Journal of Medicine.
Comparing Two Reperfusion Therapies
Because of the lack of randomized clinical trial data, it was uncertain whether endovascular therapy, including endovascular pharmacologic thrombolysis and stent retrievers, alone or combined with IV t-PA is a more effective treatment for acute stroke than IV t-PA alone, “the only proven reperfusion therapy for acute ischemic stroke,” said Dr. Broderick.
In the IMS III study, which was conducted at 58 centers in the United States, Canada, Australia, and Europe, 434 patients were randomized to endovascular therapy plus IV t-PA, and 222 were randomized to standard treatment with IV t-PA alone. Treatment began within three hours of stroke onset. Patients’ median age was approximately 68 (range, 23 to 89). More than half of patients were men, approximately 14% were black or Hispanic, and the median NIH Stroke Scale (NIHSS) score was 17. At the beginning of the study, only one thrombectomy device had been approved by the FDA. As the trial continued, the researchers used other devices as they were approved.
Time to Endovascular Therapy Did Not Affect Outcomes
The investigators observed no differences in the primary outcome (ie, mRS of 2 or less at 90 days) between patients with an NIHSS score of 20 or greater and patients with an NIHSS score of 19 or less. The neurologists had hypothesized that endovascular therapy would have greater efficacy in patients with severe strokes, because these patients “have the highest likelihood of occlusion in a major intracranial artery and the greatest volume of ischemic brain at risk.”
The researchers also had hypothesized that receiving endovascular therapy earlier rather than later would be associated with a greater benefit. Time of endovascular therapy was not a significant factor in outcomes, however.
Mortality at 90 days was 19.1% in the endovascular therapy group and 21.6% in the IV t-PA–alone group. Within 30 hours of t-PA initiation, 6.2% of subjects who received endovascular therapy and 5.9% of subjects who received t-PA alone had a symptomatic intracerebral hemorrhage. The differences in mortality at seven days and in the parenchymal hematoma rate also were not significantly different between the two groups. The rate of asymptomatic intracerebral hemorrhage, however, was significantly higher in the endovascular group.
Outcomes of combined therapy tended to be better in patients with strokes that involved larger artery occlusions and in patients with the shortest times from stroke onset to initiation of treatment. Because of the small patient population, however, the differences did not achieve statistical significance. These subgroups should be the focus of future clinical trials, said Dr. Broderick.
Endovascular Therapy Provided More Effective Recanalization Than t-PA
The predicted advantage of combined therapy was that IV t-PA could be started quickly in the emergency department, while endovascular therapy, which requires time to mobilize the interventional team, would increase the likelihood of early recanalization.
The study results provided further evidence that endovascular therapy is more effective than IV t-PA at achieving recanalization. The rate of partial or complete recanalization at 24 hours for an occlusion in the internal carotid artery was 81% in patients who received combined therapy, compared with 35% in patients who received IV t-PA alone. The higher recanalization rate among patients who received endovascular therapy did not entail a clinical benefit, however. This result may have occurred because recanalization occurred too late—after ischemia had turned into infarction, explained Dr. Broderick.
“IMS III is going to be disappointing for a lot of people who are proponents of endovascular therapy. However, there is a light at the end of the tunnel, in that there are these subgroups who may benefit,” said Brian Silver, MD, Director of the Stroke Center at Brown University in Providence, Rhode Island, who was not involved in the trial.