Fingolimod Enhances the Efficacy of Delayed Alteplase Administration in Acute Ischemic Stroke by Promoting Anterograde Reperfusion and Retrograde Collateral Flow
Department
neurology
Document Type
Article
Abstract
Objective: The present study was undertaken to determine the efficacy of coadministration of fingolimod with alteplase in acute ischemic stroke patients in a delayed time window. Methods: This was a prospective, randomized, open-label, blinded endpoint clinical trial, enrolling patients with internal carotid artery or middle cerebral artery proximal occlusion within 4.5 to 6 hours from symptom onset. Patients were randomly assigned to receive alteplase alone or alteplase with fingolimod. All patients underwent pretreatment and 24-hour noncontrast computed tomography (CT)/perfusion CT/CT angiography. The coprimary endpoints were the decrease of National Institutes of Health Stroke Scale scores over 24 hours and the favorable shift of modified Rankin Scale score (mRS) distribution at day 90. Exploratory outcomes included vessel recanalization, anterograde reperfusion, and retrograde reperfusion of collateral flow. Results: Each treatment group included 23 patients. Compared with alteplase alone, patients receiving fingolimod plus alteplase exhibited better early clinical improvement at 24 hours and a favorable shift of mRS distribution at day 90. In addition, patients who received fingolimod and alteplase exhibited a greater reduction in the perfusion lesion accompanied by suppressed infarct growth by 24 hours. Fingolimod in conjunction with alteplase significantly improved anterograde reperfusion of downstream territory and prevented the failure of retrograde reperfusion from collateral circulation. Interpretation: Fingolimod may enhance the efficacy of alteplase administration in the 4.5- to 6-hour time window in patients with a proximal cerebral arterial occlusion and salvageable penumbral tissue by promoting both anterograde reperfusion and retrograde collateral flow. These findings are instructive for the design of future trials of recanalization therapies in extended time windows. Ann Neurol 2018;84:725€“736.
Medical Subject Headings
neurology
Publication Date
2018
Publication Title
Annals of Neurology
ISSN
0364-5134
Volume
84
Issue
5
First Page
717
Last Page
728
Digital Object Identifier (DOI)
10.1002/ana.25352
Recommended Citation
Tian, De Cai; Shi, Kaibin; Zhu, Zilong; Yao, Jia; Yang, Xiaoxia; Su, Lei; Zhang, Sheng; Zhang, Meixia; Gonzales, Rayna J.; Liu, Qiang; Huang, De Ren; Waters, Michael F.; Sheth, Kevin N.; Ducruet, Andrew F.; Fu, Ying; Lou, Min; and Shi, Fu-Dong, "Fingolimod Enhances the Efficacy of Delayed Alteplase Administration in Acute Ischemic Stroke by Promoting Anterograde Reperfusion and Retrograde Collateral Flow" (2018). Neurology. 292.
https://scholar.barrowneuro.org/neurology/292