Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis.
Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation.



To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage.



Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites.



Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment.



The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation.



Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, -6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, -5.2% [95% CI, -8.3% to -2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, -0.9% to 4.2%]).



In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.
David Geffen School of Medicine, University of California-Los Angeles, Los Angeles.
Jeffrey L
JL
Saver
University of Calgary, Calgary, Alberta, Canada.
Mayank
M
Goyal
Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Aad
A
van der Lugt
University of Calgary, Calgary, Alberta, Canada.
Bijoy K
BK
Menon
Academic Medical Center, Amsterdam, the Netherlands.
Charles B L M
CB
Majoie
Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Diederik W
DW
Dippel
University of Melbourne, Melbourne, Australia.
Bruce C
BC
Campbell
Grady Memorial Hospital, Emory University School of Medicine, Atlanta, Georgia.
Raul G
RG
Nogueira
University of Calgary, Calgary, Alberta, Canada.
Andrew M
AM
Demchuk
Hospital Vall d'Hebron, Barcelona, Spain.
Alejandro
A
Tomasello
Hospital de Bellvitge, L'Hospet de Llobregat, Barcelona, Spain.
Pere
P
Cardona
Erlanger Hospital at the University of Tennessee, Chattanooga.
Thomas G
TG
Devlin
Swedish Medical Center, Englewood, Colorado.
Donald F
DF
Frei
Klinikum der Goethe-Universität, Frankfurt, Germany.
Richard
R
du Mesnil de Rochemont
Academic Medical Center, Amsterdam, the Netherlands.
Olvert A
OA
Berkhemer
University of Pittsburgh Medical Center, Pittsburgh, Pennyslvania.
Tudor G
TG
Jovin
State University of New York at Buffalo, Buffalo.
Adnan H
AH
Siddiqui
Maastricht University Medical Center, Maastricht, the Netherlands.
Wim H
WH
van Zwam
University of Melbourne, Melbourne, Australia.
Stephen M
SM
Davis
Hospital Germans Trias i Pujol, Barcelona, Spain.
Carlos
C
Castaño
Erlanger Medical Center, Chattanooga, Tennessee.
Biggya L
BL
Sapkota
Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Puck S
PS
Fransen
Hospital Vall d'Hebron, Barcelona, Spain.
Carlos
C
Molina
Maastricht University Medical Center, Maastricht, the Netherlands.
Robert J
RJ
van Oostenbrugge
Hospital Clinic de Barcelona, Barcelona, Spain.
Ángel
Á
Chamorro
Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Hester
H
Lingsma
University Health Network, Toronto, Ontario, Canada.
Frank L
FL
Silver
Florey Institute, Melbourne, Australia.
Geoffrey A
GA
Donnan
University of Alberta, Edmonton, Alberta, Canada.
Ashfaq
A
Shuaib
Altair Biostatistics, St Louis Park, Minnesota.
Scott
S
Brown
Philadelphia College of Osteopathic Medicine, Philadelphia, Pennyslvania.
Bruce
B
Stouch
University of Melbourne, Melbourne, Australia.
Peter J
PJ
Mitchell
Hospital Germans Trias i Pujol, Barcelona, Spain.
Antoni
A
Davalos
Academic Medical Center, Amsterdam, the Netherlands.
Yvo B W E M
YB
Roos
University of Calgary, Calgary, Alberta, Canada.
Michael D
MD
Hill
D000368:Aged; D002545:Brain Ischemia; D057510:Endovascular Procedures / Q000379:methods*; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages; D008297:Male; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D015424:Reperfusion; D015607:Stents; D020521:Stroke / Q000628:therapy*; D017131:Thrombectomy / Q000379:methods*; D061665:Time-to-Treatment; D016896:Treatment Outcome