Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).

Association between intravenous tirofiban and intracranial hemorrhage in acute large vessel occlusion stroke: insight from the RESCUE BT randomized placebo-controlled trial.

BACKGROUND: The aim of this study is to investigate the association between intravenous tirofiban and symptomatic intracranial hemorrhage (SICH) in patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) receiving endovascular thrombectomy (EVT) within 24 h of time last known well (LKW). METHODS: Patients with AIS-LVO who were randomly assigned to receive intravenous tirofiban or placebo before EVT within 24 h of time LKW and had follow-up brain non-contrast computed tomography within 24 h after stopping tirofiban treatment were derived from "RESCUE BT": a multicenter, randomized, placebo-controlled, double-blind trial. All eligible patients were divided into SICH and NO-SICH groups. Subgroup analyses were performed to explore for heterogeneity. RESULTS: Of 945 patients included in this cohort, there were 76 (8.0%) in the SICH group and 869 (92.0%) in the NO-SICH group. The incidence of SICH was not higher in patients receiving intravenous tirofiban compared with placebo (adjusted risk ratio (RR), 1.51; 95% confidence interval (CI), 0.97-2.36; P = 0.07). Subgroup analyses showed that age greater than 67-year-old (adjusted RR, 2.18; 95% CI 1.18-4.00), NIHSS greater than 16 (adjusted RR, 1.88; 95% CI 1.06-3.34), and cardioembolism (adjusted RR, 3.73; 95% CI 1.66-8.35) were associated with increased SICH risk. CONCLUSIONS: In patients with acute large vessel occlusion stroke, intravenous tirofiban before EVT within 24 h of time from last known well is not associated with increased risk of SICH. Patients who are older, have more severe neurological deficits, or with cardioembolism are at higher risk of SICH with intravenous tirofiban. TRIAL REGISTRATION NUMBER: URL: http://www.chictr.org.cn ; Unique identifier: ChiCTR-INR-17014167.