By Matthew E. Fink, MD
Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, New York Presbyterian/Weill Cornell Medical College
SOURCE: Zi W, Song J, Kong W, et al. Tirofiban for stroke without large or medium-sized vessel occlusion. N Engl J Med 2023;388:2025-2036.
Patients who arrive at the hospital with acute ischemic stroke must receive intravenous thrombolysis within several hours or undergo endovascular thrombectomy if they have large vessel occlusion. However, a large proportion of ischemic stroke patients do not fit into either category, and treatment options are limited. In addition, there are some patients who are treated with intravenous thrombolysis early, but who then progress over the next 24 hours.
Glycoprotein IIb/IIIa receptor inhibitors are potent, rapidly acting antiplatelet agents that have been tried in pilot studies to treat acute ischemic stroke, without significant benefit. Tirofiban is fast-acting, highly selective, and has a short half-life that allows bleeding time to return to normal within three hours after administration is stopped. The investigators proposed that this medication may be of benefit in patients with acute ischemic stroke who arrived within 24 hours after stroke onset but are not eligible for thrombolysis or thrombectomy or have progression of stroke symptoms after receiving thrombolysis.
This was a multicenter clinical trial in China, with enrollment of patients who had acute ischemic stroke without large vessel occlusion, and a National Institutes of Health Stroke Scale score of 5 or higher. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy but within 24 hours of last known well, progression of stroke symptoms 24 to 96 hours after onset, early neurological deterioration after thrombolysis, or thrombolysis with no improvement at four to 24 hours.
Patients were assigned to receive intravenous tirofiban or oral aspirin for two days. All patients received oral aspirin until day 90. The primary outcome was excellent outcome as defined by a score of 0-1 on a modified Rankin Scale at 90 days. Secondary endpoints included functional independence at 90 days in the quality-of-life score. Safety endpoints were death and symptomatic intracranial hemorrhage.
A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most of the strokes are presumed to be atherosclerotic. At 90 days, 29.1% of patients treated with tirofiban had a modified Rankin Scale score of 0-1, as did 22.2% of patients treated with aspirin. Secondary endpoints were not consistent with the results of the primary analysis. Mortality was similar in both groups. The incidence of symptomatic intracranial hemorrhage was 1% in the tirofiban group and 0% in the aspirin group.
In this trial of patients with ischemic stroke of recent onset or progression of stroke symptoms in nonoccluded large vessels, intravenous tirofiban was associated with a greater likelihood of excellent outcome compared to low-dose aspirin. This study was performed exclusively in China and should be repeated with a more diverse population of patients to avoid any confounding factors related to the population being studied.
