Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population.
BACKGROUND
Earlier tissue plasminogen activator treatment improves ischemic stroke outcome, but aspects of the time-benefit relationship still not well delineated are: (1) the degree of additional benefit accrued with treatment in the first 60 minutes after onset, and (2) the shape of the time-benefit curve through 4.5 hours.


METHODS
We analyzed patients who had acute ischemic stroke treated with intravenous tissue plasminogen activator within 4.5 hours of onset from the Get With The Guidelines-Stroke US national program. Onset-to-treatment time was analyzed as a continuous, potentially nonlinear variable and as a categorical variable comparing patients treated within 60 minutes of onset with later epochs.


RESULTS
Among 65 384 tissue plasminogen activator-treated patients, the median onset-to-treatment time was 141 minutes (interquartile range, 110-173) and 878 patients (1.3%) were treated within the first 60 minutes. Treatment within 60 minutes, compared with treatment within 61 to 270 minutes, was associated with increased odds of discharge to home (adjusted odds ratio, 1.25; 95% confidence interval, 1.07-1.45), independent ambulation at discharge (adjusted odds ratio, 1.22; 95% confidence interval, 1.03-1.45), and freedom from disability (modified Rankin Scale 0-1) at discharge (adjusted odds ratio, 1.72; 95% confidence interval, 1.21-2.46), without increased hemorrhagic complications or in-hospital mortality. The pace of decline in benefit of tissue plasminogen activator from onset-to-treatment times of 20 through 270 minutes was mildly nonlinear for discharge to home, with more rapid benefit loss in the first 170 minutes than later, and linear for independent ambulation and in-hospital mortality.


CONCLUSIONS
Thrombolysis started within the first 60 minutes after onset is associated with best outcomes for patients with acute ischemic stroke, and benefit declined more rapidly early after onset for the ability to be discharged home. These findings support intensive efforts to organize stroke systems of care to improve the timeliness of thrombolytic therapy in acute ischemic stroke.
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Joon-Tae
JT
Kim
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Gregg C
GC
Fonarow
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Eric E
EE
Smith
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Mathew J
MJ
Reeves
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Digvijaya D
DD
Navalkele
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
James C
JC
Grotta
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Maria V
MV
Grau-Sepulveda
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Adrian F
AF
Hernandez
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Eric D
ED
Peterson
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.).
Lee H
LH
Schwamm
From Department of Neurology, Chonnam National University Hospital, Gwangju, Korea (J.-T.K.); Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (G.C.F.); Hotchkiss Brain Institute, University of Calgary, Alberta, Canada (E.E.S.); Department of Epidemiology and Biostatistics, Michigan State University, East Lansing (M.J.R.); Department of Neurology, University of Texas Health Science Center, Houston (D.D.N.); Clinical Innovation and Research Institute, Memorial Hermann Hospital, Houston, TX (J.C.G.); Outcome Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (M.V.G.-S., A.F.H., E.D.P.); Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston (L.H.S.); and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles (J.L.S.). jsaver@mednet.ucla.edu.
Jeffrey L
JL
Saver
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods; D061665:Time-to-Treatment; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
stroke; thrombolytic therapy; time-benefit curve; tissue plasminogen activator