Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow

De Cai Tian, Kaibin Shi, Zilong Zhu, Jia Yao, Xiaoxia Yang, Lei Su, Sheng Zhang, Meixia Zhang, Rayna J Gonzales, Qiang Liu, De Ren Huang, Michael F. Waters, Kevin N. Sheth, Andrew F. Ducruet, Ying Fu, Min Lou, Fu Dong Shi

Research output: Contribution to journalArticle

3 Citations (Scopus)

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;1–12.

Original languageEnglish (US)
JournalAnnals of Neurology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Tissue Plasminogen Activator
Reperfusion
Stroke
Perfusion
Tomography
Collateral Circulation
Fingolimod Hydrochloride
Middle Cerebral Artery Infarction
National Institutes of Health (U.S.)
Internal Carotid Artery
Clinical Trials
Therapeutics
Growth

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow. / 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; Shi, Fu Dong.

In: Annals of Neurology, 01.01.2018.

Research output: Contribution to journalArticle

Tian, DC, Shi, K, Zhu, Z, Yao, J, Yang, X, Su, L, Zhang, S, Zhang, M, Gonzales, RJ, Liu, Q, Huang, DR, Waters, MF, Sheth, KN, Ducruet, AF, Fu, Y, Lou, M & Shi, FD 2018, 'Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow', Annals of Neurology. https://doi.org/10.1002/ana.25352
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 ; Shi, Fu Dong. / Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow. In: Annals of Neurology. 2018.
@article{d21276356fc14b91a77b4f38395edb49,
title = "Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow",
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;1–12.",
author = "Tian, {De Cai} and Kaibin Shi and Zilong Zhu and Jia Yao and Xiaoxia Yang and Lei Su and Sheng Zhang and Meixia Zhang and Gonzales, {Rayna J} and Qiang Liu and Huang, {De Ren} and Waters, {Michael F.} and Sheth, {Kevin N.} and Ducruet, {Andrew F.} and Ying Fu and Min Lou and Shi, {Fu Dong}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/ana.25352",
language = "English (US)",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow

AU - Tian, De Cai

AU - Shi, Kaibin

AU - Zhu, Zilong

AU - Yao, Jia

AU - Yang, Xiaoxia

AU - Su, Lei

AU - Zhang, Sheng

AU - Zhang, Meixia

AU - Gonzales, Rayna J

AU - Liu, Qiang

AU - Huang, De Ren

AU - Waters, Michael F.

AU - Sheth, Kevin N.

AU - Ducruet, Andrew F.

AU - Fu, Ying

AU - Lou, Min

AU - Shi, Fu Dong

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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;1–12.

AB - 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;1–12.

UR - http://www.scopus.com/inward/record.url?scp=85055938090&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055938090&partnerID=8YFLogxK

U2 - 10.1002/ana.25352

DO - 10.1002/ana.25352

M3 - Article

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

ER -