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Original Investigation
July 16, 2019

Association Between Time to Treatment With Endovascular Reperfusion Therapy and Outcomes in Patients With Acute Ischemic Stroke Treated in Clinical Practice

Author Affiliations
  • 1Division of Interventional Neuroradiology, David Geffen School of Medicine, University of California, Los Angeles
  • 2Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles
  • 3Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts
  • 4Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles
  • 5Duke Clinical Research Center, Durham, North Carolina
  • 6Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina
  • 7Department of Neurology, University of Miami Health System, Miami, Florida
  • 8Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
JAMA. 2019;322(3):252-263. doi:10.1001/jama.2019.8286
Key Points

Question  What is the relation between time to treatment and outcome from endovascular-recanalization therapy for acute ischemic stroke (AIS)?

Findings  In this retrospective cohort study of 6756 patients with AIS in a US nationwide clinical registry, earlier onset to treatment was associated with improved outcomes, including, for every 15 minutes faster treatment: higher rates of independent ambulation (absolute increase, 1.14%), functional independence at discharge (absolute increase, 0.91%), and lower mortality/hospice discharge (absolute decrease, −0.77%).

Meaning  Among patients with AIS treated in routine clinical practice, shorter time to endovascular-recanalization therapy was associated with better outcomes.


Importance  Randomized clinical trials suggest benefit of endovascular-reperfusion therapy for large vessel occlusion in acute ischemic stroke (AIS) is time dependent, but the extent to which it influences outcome and generalizability to routine clinical practice remains uncertain.

Objective  To characterize the association of speed of treatment with outcome among patients with AIS undergoing endovascular-reperfusion therapy.

Design, Setting, and Participants  Retrospective cohort study using data prospectively collected from January 2015 to December 2016 in the Get With The Guidelines-Stroke nationwide US quality registry, with final follow-up through April 15, 2017. Participants were 6756 patients with anterior circulation large vessel occlusion AIS treated with endovascular-reperfusion therapy with onset-to-puncture time of 8 hours or less.

Exposures  Onset (last-known well time) to arterial puncture, and hospital arrival to arterial puncture (door-to-puncture time).

Main Outcomes and Measures  Substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), ambulatory status, global disability (modified Rankin Scale [mRS]) and destination at discharge, symptomatic intracranial hemorrhage (sICH), and in-hospital mortality/hospice discharge.

Results  Among 6756 patients, the mean (SD) age was 69.5 (14.8) years, 51.2% (3460/6756) were women, and median pretreatment score on the National Institutes of Health Stroke Scale was 17 (IQR, 12-22). Median onset-to-puncture time was 230 minutes (IQR, 170-305) and median door-to-puncture time was 87 minutes (IQR, 62-116), with substantial reperfusion in 85.9% (5433/6324) of patients. Adverse events were sICH in 6.7% (449/6693) of patients and in-hospital mortality/hospice discharge in 19.6% (1326/6756) of patients. At discharge, 36.9% (2132/5783) ambulated independently and 23.0% (1225/5334) had functional independence (mRS 0-2). In onset-to-puncture adjusted analysis, time-outcome relationships were nonlinear with steeper slopes between 30 to 270 minutes than 271 to 480 minutes. In the 30- to 270-minute time frame, faster onset to puncture in 15-minute increments was associated with higher likelihood of achieving independent ambulation at discharge (absolute increase, 1.14% [95% CI, 0.75%-1.53%]), lower in-hospital mortality/hospice discharge (absolute decrease, −0.77% [95% CI, −1.07% to −0.47%]), and lower risk of sICH (absolute decrease, −0.22% [95% CI, −0.40% to −0.03%]). Faster door-to-puncture times were similarly associated with improved outcomes, including in the 30- to 120-minute window, higher likelihood of achieving discharge to home (absolute increase, 2.13% [95% CI, 0.81%-3.44%]) and lower in-hospital mortality/hospice discharge (absolute decrease, −1.48% [95% CI, −2.60% to −0.36%]) for each 15-minute increment.

Conclusions and Relevance  Among patients with AIS due to large vessel occlusion treated in routine clinical practice, shorter time to endovascular-reperfusion therapy was significantly associated with better outcomes. These findings support efforts to reduce time to hospital and endovascular treatment in patients with stroke.