Tirofiban on First-Pass Recanalization in Acute Stroke Endovascular Thrombectomy: The OPTIMISTIC Randomized Clinical Trial

Abstract

Importance: Tirofiban is a nonpeptide antagonist of the glycoprotein IIb/IIIa receptor that inhibits platelet aggregation selectively. Despite widespread use in acute ischemic stroke in conjunction with endovascular treatment, the role of tirofiban is uncertain.

Objective: To assess whether intravenous tirofiban initiated before endovascular thrombectomy improves thrombectomy outcomes by achieving first-pass recanalization without intracranial hemorrhagic risk.

Design, setting, and participants: This was a multicenter, prospective, open-label, blinded, end point phase 2 randomized clinical trial that enrolled patients from 7 Chinese hospital stroke centers between April 30, 2021, and July 16, 2023. Eligible patients were aged 18 to 85 years with large vessel occlusion (internal carotid artery or M1 or M2 segment of middle cerebral artery) and were considered for endovascular thrombectomy within 24 hours of ischemic stroke onset or last known well time. Patients with a history of atrial fibrillation or treated with intravenous thrombolysis were excluded.

Intervention: Patients were randomly assigned (1:1) to intravenous tirofiban (10 μg/kg bolus plus 0.1 μg/kg per minute infusion for 24 hours) or standard care before endovascular thrombectomy using a web-based, computer-generated randomization procedure.

Main outcomes and measures: The primary outcome was the proportion of patients achieving first-pass recanalization without symptomatic intracranial hemorrhage. First-pass recanalization was assessed by reviewers blinded to treatment allocation and predefined as successful recanalization of a targeted vessel after a single pass of thrombectomy. The primary outcome was analyzed by modified Poisson regression with robust error estimation, adjusting for time from onset or last known well time to randomization and vessel occlusion site.

Results: Among 200 patients randomized (median age, 66 years [IQR, 58-72 years]; 146 male [73%]), 102 were allocated to receive intravenous tirofiban, and 98 were allocated to receive standard care before endovascular thrombectomy. In the intention-to-treat analysis, 64 of 99 patients receiving tirofiban (65%) and 46 of 95 control patients (48%) achieved the primary outcome of first-pass recanalization without symptomatic intracranial hemorrhage (adjusted risk ratio, 1.34 [95% CI, 1.04-1.73]; P = .03). Incidence of symptomatic intracranial hemorrhage was 0% (0 of 101 patients) in the tirofiban group vs 6% (6 of 98 patients) in the control group (unadjusted risk difference, -0.06 [95% CI, -0.11 to -0.01]).

Conclusions and relevance: In this randomized clinical trial of patients who had acute ischemic stroke with no history of atrial fibrillation and no prior intravenous thrombolysis, intravenous tirofiban administered before endovascular thrombectomy increased the likelihood of first-pass recanalization without symptomatic intracranial hemorrhage. These findings suggest that neurointerventionalists may consider this pre-procedure antiplatelet treatment to facilitate endovascular thrombectomy.

Trial registration: ClinicalTrials.gov Identifier: NCT04851457.

Figure 1.. Patient Flow Diagram for the One Pass Tirofiban in Management of Ischemic Stroke Thrombectomy in China (OPTIMISTIC) Randomized Clinical Trial

CT indicates computed tomography; ICA, internal carotid artery; MRI, magnetic resonance imaging; mRS, modified Rankin Scale (scores range from 0 to 6, with lower scores indicating less disability); NIHSS, National Institutes of Health Stroke Scale (scores range from 0 to 42, with higher scores indicating greater neurologic deficit). ^aMultimodal CT or MRI criteria: ischemic penumbra, more than 10 mL; infarct core, less than 70 mL; and mismatch ratio, more than 1.2.

Figure 2.. Forest Plot of the Primary Outcome Stratified by Prespecified Subgroups in the Intention-to-Treat Population

Primary outcome data were not available for 6 patients (3 in the tirofiban group and 3 in the control group), and intracranial atherosclerotic disease (ICAD) classification was not available for an additional 4 patients without residual stenosis information (2 in the tirofiban group and 2 in the control group). ARR indicates adjusted risk ratio; ICA, internal carotid artery.