Early endovascular thrombectomy after t-PA may improve reperfusion, early neurologic recovery, and functional outcome, compared with t-PA alone, for patients with ischemic stroke who have major arterial occlusion and salvageable tissue on CT perfusion imaging, according to a study published online ahead of print February 11 in the New England Journal of Medicine. The study is called the Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA) trial.
Three major stroke trials completed in 2013 did not support endovascular therapy for acute ischemic stroke. The recent MR CLEAN study, however, suggested that the therapy is safe and effective. The EXTEND-IA trial provides further evidence of the treatment’s potential benefits for patients with ischemic stroke.
Bruce Campbell, MD, a neurologist at Royal Melbourne Hospital in Australia, and colleagues randomized patients to t-PA and clot retrieval with the Solitaire FR device or t-PA alone. The dose of t-PA for all patients was 0.9 mg/kg, and the drug was administered less than 4.5 hours after stroke onset. Endovascular therapy was initiated within six hours of stroke onset. Eligible participants had occlusion of the internal carotid or middle cerebral artery, an ischemic core volume of less than 70 mL, and salvageable tissue on CT perfusion.
The trial’s primary outcomes were the proportion of the perfusion lesion reperfused at 24 hours on CT or MR perfusion imaging, and the proportion of patients with early neurologic improvement. Early neurologic improvement was defined as a reduction in NIH Stroke Scale (NIHSS) score of eight or more points, or as a score of 0 or 1, by day three. The study’s secondary outcome was ordinal analysis of modified Rankin Scale (mRS) score at 90 days.
The researchers intended to randomize 100 patients, but the data safety and monitoring committee stopped the trial after 70 patients had been randomized because of the study treatment’s overwhelming efficacy. The committee’s action followed a review of the trial that had been prompted by the publication of the results of the MR CLEAN study.
In all, 35 patients received t-PA and endovascular treatment, and 35 patients received t-PA alone. In the intervention group, mean age was 68.6, median NIHSS score was 17, and median time to recanalization was 259 min. In the control group, mean age was 70.2 and median NIHSS score was 13.
Participants who received endovascular treatment had greater median reperfusion at 24 hours than patients who received t-PA alone (100% vs 37%). Of those patients who received endovascular treatment, 80% had early neurologic improvement, compared with 37% of those who received t-PA alone. Approximately 71% of people who received endovascular treatment achieved functional independence (ie, mRS score of 0 to 2) at 90 days, compared with 40% of patients who received t-PA alone.
Symptomatic intracerebral hemorrhage occurred in no patients who received endovascular treatment and two patients who received t-PA alone. Complications of endovascular treatment included one wire perforation and one groin hematoma.
Together with the MR CLEAN study, the EXTEND-IA trial is a “game-changer” in the treatment of stroke, said Peter Mitchell, MD, Director of Neurointervention Service at the Royal Melbourne Hospital and a study investigator. “The patients treated in EXTEND-IA had even better outcomes than [those] in MR CLEAN,” he added. “The key differences were improved rates of opening the blocked blood vessel, earlier treatment, and the use of more advanced brain imaging to select patients most likely to benefit.
“The challenge now is to implement stent thrombectomy as a standard treatment for stroke,” Dr. Mitchell said.