In a randomized trial of patients with acute ischemic stroke, patients receiving endovascular treatment fared no better at 90 days than patients who underwent intravenous thrombolytic therapy. These results were published online ahead of print Feb. 6 in the New England Journal of Medicine.
Noting that endovascular treatment of ischemic stroke leads to increased recanalization when compared with intravenous thrombolysis, Alfonso Ciccone, MD, of the stroke unit and department of neurology at Niguarda Ca’ Granda Hospital in Milan, Italy, and colleagues set out to assess whether endovascular treatment led to better outcomes. This was a multicenter, open treatment trial with a blinded endpoint.
Between Feb. 1, 2008, and April 16, 2012, the researchers randomized 362 patients between the ages of 18 and 80 presenting with ischemic stroke and with clearly defined onset of symptoms such that recombinant tissue plasminogen activator (t-PA) could be administered within 4.5 hours, and endovascular intervention could occur within six hours of onset of symptoms.
Patients receiving t-PA were started on thrombolysis immediately upon randomization; they received intravenous doses of 0.9mg/Kg, 10 percent given as an initial bolus and the remaining 90 percent infused over the course of 60 minutes.
Patients receiving endovascular treatment did not receive t-PA prior to diagnostic angiography but anticoagulant therapy was recommended. After obtaining the diagnostic information the operator could choose pharmacologic or mechanical thrombolysis or both. If the patient received pharmacologic thrombolysis, the dose did not exceed 0.9mg/Kg delivered over 60 minutes. If the patient achieved complete recanalization prior to 60 minutes, the dose was stopped.
If the angiography revealed no current occlusion, the operator injected t-PA into the presumably affected vessels. The dose was at the operator’s discretion but did not exceed 0.9/mg/Kg. Patients without neurologic deficits did not receive t-PA.
The researchers conducted a neurologic assessment using the 42-point National Institutes of Health Stroke Scale (NIHSS) at baseline and at day seven or upon discharge or transfer, whichever came first. A neurologist conducted a phone interview with the patient, or if the patient was unavailable, a proxy, to assess neurologic condition at 90 days. The interviewing neurologist assigned a rating on the Rankin Scale, with 0 indicating no symptoms and 6 indicating death.
The primary outcome was survival free of disability at 90 days; the researchers defined freedom from disability as a Rankin score of 0 or 1. Safety outcomes were fatal and non-fatal symptomatic intracranial hemorrhage, fatal and non-fatal symptomatic edema from brain infarction, fatal and non-fatal recurrent ischemic stroke, any cause death, neurologic deterioration (increase of four or more points in NIHSS score), and fatal and non-fatal extracerebral events.
Patients in the endovascular treatment group survived 90 days without disability at a rate of 30.4 percent, compared to 34.8 percent of patients in the t-PA group. Death occurred in 14.4 percent of the endovascular patients compared with 9.9 percent of the t-PA group. The researchers reported no differences in the incidence of safety endpoints between the two groups.
The trial was powered to find a 15 percent advantage for endovascular treatment for the primary outcome, and it “failed to show the superiority of endovascular therapy as compared with intravenous t–PA,” the authors wrote. Furthermore, subgroup analysis “suggested that the lack of superiority of endovascular treatment did not depend on the time to endovascular treatment, the stroke subtype, or the type of center.”
The authors noted that a larger sample size may have allowed them to draw more distinctions within subgroups. Still, “our findings do not provide support for the use of the more invasive and expensive endovascular therapy over intravenous treatment,” they concluded.
The Italian Medicines Agency funded the study.