The “Golden Hour” and Acute Brain Ischemia

Presenting Features and Lytic Therapy in >30 000 Patients Arriving

Within 60 Minutes of Stroke Onset
Jeffrey L. Saver, MD; Eric E. Smith, MD, MPH; Gregg C. Fonarow, MD; Mathew J. Reeves, PhD;
Xin Zhao, MS; DaiWai M. Olson, PhD, RN; Lee H. Schwamm, MD;
on behalf of the GWTG-Stroke Steering Committee and Investigators

Background and Purpose—The benefit of intravenous thrombolytic therapy in acute brain ischemia is strongly time
dependent.
Methods—The Get With the Guidelines–Stroke database was analyzed to characterize ischemic stroke patients arriving at
hospital Emergency Departments within 60 minutes of the last known well time from April 1, 2003, to December 30, 2007.
Results—During the 4.75-year study period, among 253 148 ischemic stroke patients arriving directly by ambulance or
private vehicle at 905 hospital Emergency Departments, 106 924 (42.2%) had documented, exact last known well times.
Onset to door time was ⱕ60 minutes in 30 220 (28.3%), 61 to 180 minutes in 33 858 (31.7%), and ⬎180 minutes in
42 846 (40.1%). Features most strongly distinguishing the patients arriving at ⱕ60, 61 to 180, and ⬎180 minutes were
greater stroke severity (median National Institutes of Health Stroke Scale score, 8.0 vs 6.0 vs 4.0, P⬍0.0001) and more
frequent arrival by ambulance (79.0%. vs 72.2% vs 55.0%, P⬍0.0001). Compared with patients arriving at 61 to 180
minute, “golden hour” patients received intravenous thrombolytic therapy more frequently (27.1% vs 12.9%; odds
ratio⫽2.51; 95% CI, 2.41–2.61; P⬍0.0001), but door-to-needle time was longer (mean, 90.6 vs 76.7 minutes,
P⬍0.0001). A door-to-needle time of ⱕ60 minutes was achieved in 18.3% of golden hour patients.
Conclusions—At Get With the Guidelines-Stroke hospital Emergency Departments, more than one quarter of patients with
documented onset time and at least one eighth of all ischemic stroke patients arrived within 1 hour of onset, where
they received thrombolytic therapy more frequently but more slowly than late arrivers. These findings support
public health initiates to increase early presentation and shorten door-to-needle times in patients arriving within
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the golden hour. (Stroke. 2010;41:1431-1439.)

Key Words: acute care 䡲 acute therapy 䡲 acute stroke 䡲 emergency medical services 䡲 emergency medicine
䡲 stroke care 䡲 stroke delivery 䡲 therapy 䡲 thrombolysis 䡲 thrombolytic therapy

T he benefit of intravenous (IV) thrombolytic therapy in

acute brain ischemia is strongly time dependent. Thera-
peutic yield is maximal in the first minutes after symptom
onset and declines rapidly during the next 4.5 hours.1,2 In the
typical large-artery ischemic stroke, for each minute that
reperfusion is delayed, 2 million nerve cells die.3 Among
every 100 patients treated with IV therapy, for every 10-
minute delay in the start of lytic infusion within the 1- to
3-hour treatment window, 1 fewer patient has an improved
disability outcome.2 Consequently, patients who present to
the hospital within the first 60 minutes of onset have the
greatest opportunity to benefit from recanalization therapy.
Because of the critical importance of rapid treatment, national
recommendations for hospitals that accept acute stroke pa-
tients in their Emergency Departments (EDs) are to complete
the clinical and imaging evaluation of the patient and initiate
lytic therapy within 1 hour of patient arrival.4 The Joint
Commission target for primary stroke centers is to achieve a
door-to-needle (DTN) time of within 60 minutes in 80% or
more of patients.
Originally developed in the setting of trauma treatment, the
term the “golden hour” is now a general concept in emer-
gency medicine that is applied to conditions in which hyper-
acute therapy is more effective than later intervention, including
trauma, myocardial ischemia, septic shock, cardiopulmonary
resuscitation, and stroke. The frequency, characteristics, and
treatment of ischemic stroke patients arriving at hospitals
within the golden hour nationally have not previously been
well characterized. Several large registry studies in the United
States and internationally have provided important informa-

Received March 6, 2010; final revision received March 12, 2010; accepted March 17, 2010.
From the Department of Neurology (J.L.S.), University of California, Los Angeles, Calif; Department of Clinical Neurosciences (E.E.S.), Hotchkiss
Brain Institute, University of Calgary, Calgary, Canada; Division of Cardiology (G.C.F.), University of California, Los Angeles, Calif; Department of
Epidemiology (M.J.R.), Michigan State University, East Lansing, Mich; Duke Clinical Research Center (X.Z., D.M.O.), Durham, NC; and Department
of Neurology (L.H.S.), Massachusetts General Hospital, Boston, Mass.
Correspondence to Jeffrey L. Saver, MD, UCLA Stroke Center, 710 Westwood Plaza, Los Angeles, CA 90095. E-mail jsaver@ucla.edu
© 2010 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.110.583815

1431
 1432 Stroke July 2010
tion regarding patients within the ⬍3-hour window for lytic
therapy.5–9 Of concern, cohort studies have suggested an
inverse relation between time from symptom onset to hospital
arrival and DTN time among stroke patients treated with IV
tissue plasminogen activator (TPA).9 Among patients arriving
between 100 and 130 minutes after onset, rapid ED care
occurred and DTN times less than or near 60 minutes were
often attained, permitting the start of therapy within the
180-minute limit of the drug label. In contrast, among
patients arriving early after onset, DTN times were often
extended, and therapy was frequently still not administered
until nearly the 3-hour mark. The representativeness of these
small treatment cohorts is not known.
The Get With the Guidelines(GWTG)-Stroke national
dataset offers an opportunity to examine the presenting
characteristics of ischemic stroke patients arriving within the
golden hour, factors associated with early presentation, the
rapidity of lytic care initiation, and the determinants of
efficient lytic care in a large, nationally representative cohort.
Methods
The American Heart Association and American Stroke Association
launched the GWTG-Stroke initiative focused on the redesign of
hospital systems of care to improve the quality of care of patients
with stroke and transient ischemic attack.10,11 GWTG uses a Web-
based patient management tool (Outcome Sciences, Inc, Cambridge,
Mass) to collect clinical data on consecutively admitted patients,
provide decision support, and enable real-time online reporting
features. After an initial pilot phase conducted in 8 states, the
GWTG-Stroke program was made available in April 2003 to any
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hospital in the United States.12 Data from hospitals that joined the
program any time between April 2003 and December 2007 were
included in this analysis. Each participating hospital received either
human research approval to enroll cases without individual patient
consent under the common rule or a waiver of authorization and
exemption from subsequent review by their institutional review
board. Outcome Sciences, Inc, serves as the data collection and
coordination center for GWTG. The Duke Clinical Research Institute
serves as the data analysis center and has an agreement to analyze the
aggregate deidentified data for research purposes.
Case Identification and Data Abstraction
Trained hospital personnel were instructed to ascertain consecutive
acute stroke admissions by either prospective clinical identification,
retrospective identification according to International Classification
of Diseases–9 discharge codes, or a combination. Methods used for
prospective identification varied, but they included regular surveil-
lance of ED records (ie, presenting symptoms and chief complaints),
ward census logs, and/or neurologic consultations. The eligibility of
each acute stroke admission was confirmed at chart review before
data abstraction. Patient data abstracted by the patient management
tool included demographics, medical history, initial head computed
tomography (CT) findings, in-hospital treatment and events, dis-
charge treatment, mortality, and discharge destination. Data on
hospital-level characteristics (ie, bed size, academic or nonacademic
status, annual volume of stroke discharges, and geographic region)
were collected from the American Hospital Association.13
For this study, the GWTG-Stroke database was analyzed to
characterize ischemic stroke patients arriving at hospital EDs ⱕ60
minutes compared with ⬎60 minutes after symptom onset from
April 1, 2003, to December, 30, 2007. Patient-level variables were
analyzed for all patients meeting the study entry criteria. Hospital-
level determinants were analyzed for hospitals that entered ⱖ5
patients meeting the study criteria in the database. Contingency
tables were generated to explore group differences in demographics
(age, sex), stroke severity, arrival mode (ambulance, private vehicle),
DTN time, door-to-imaging time, and outcome destination at dis-
charge. A ␹2 test for nominal data and Kruskal-Wallis tests for
ordinal and continuous data were used as tests for unadjusted
statistical associations. Statistical significance was defined as
Pⱕ0.01. Generalized estimating equations logistic-regression mod-
els, accounting for within-hospital clustering, were generated to
identify independent predictors of onset-to-door (OTD) time ⱕ60
minutes and of DTN time ⱕ60 minutes. General details of the
candidate patient and hospital variables and the modeling process
have been previously described.10 Statistical significance was de-
fined as Pⱕ0.01. All statistical analyses were performed with SAS
version 9.1 software (SAS Institute, Cary, NC).
Results
During the 4.75-year time period, at 905 hospital sites, data
for 431 170 ischemic stroke and transient ischemic attack
patients were entered into the GWTG-Stroke database. The
main analyses of this study were performed for the 106 924
patients in this cohort with ischemic stroke, a documented last
known well time (LKWT), and presentation directly to the
ED by ambulance or private vehicle. Among excluded
patients were 74 671 who did not present directly to the ED
(including in-hospital stroke, elective admission directly to
the hospital, or secondary transfer from another hospital);
103 351 ED-arriving patients with final diagnoses of transient
ischemic attack; and 146 224 direct ED-arriving ischemic
stroke patients for whom the LKWT was not documented.
Patient- and hospital-level characteristics among patients
with and without a documented LKWT are shown in Table 1.
Large differences were noted in arrival by emergency medi-
cal services and use of TPA (both higher in documented
LKWT patients) and modest differences in other features,
including stroke severity (higher in documented LKWT
patients) and race (lower frequency of blacks in documented
LKWT patients).
Among the direct ED-arriving ischemic stroke patients
with a documented LKWT, OTD time was 60 minutes or less
in 30 220 (28.3%), 61 to 180 minutes in 33 858 (31.7%), and
⬎180 minutes in 42 846 (40.1%). Among the subgroup
who arrived within 60 minutes, mean OTD time was 39.9
minutes (SD, 14.8). In the most recent study year, 2007,
among the 809 facilities contributing data, GWTG-Stroke
hospitals cared for 10 497 golden hour–arriving ischemic
stroke patients.
Table 2 shows patient- and hospital-level characteristics of
3 ischemic stroke time-of-arrival cohorts. All groups were
similar in age and sex. In terms of race-ethnicity, patients
arriving in ⱕ1 hour and in 1 to 3 hours, compared with those
arriving ⬎3 hours, were slightly more often non-Hispanic
whites and less often black or Asian. Among those patients in
whom stroke severity was documented (n⫽51 738), severity
was greatest among golden hour–arriving patients (median
National Institutes of Health Stroke Scale [NIHSS]score 8),
intermediate among 1- to 3-hour–arriving patients (NIHSS
score 6), and least among those arriving ⬎3 hours (NIHSS
score 4). A similar graded difference was observed in the
frequency of arrival at the hospital by ambulance, which
occurred in 79.0% of patients arriving in 1 hour or less, in
72.2% of 1- to 3-hour–arriving patients, and in 55.0% of
⬎3-hour–arriving patients. Considering hospital characteris-
 Saver et al The “Golden Hour” in Ischemic Stroke 1433

Table 1. Patient- and Hospital-Level Characteristics of atherosclerotic risk factors (hypertension, tobacco use, and
Ischemic Stroke Patients With and Without Documented LKWTs diabetes). Hospital factors associated with decreasing odds of
LKWT LKWT Not golden hour arrival included hospital location in the South
Documented Documented P Value (US Census region definition) and higher annual number of
n 106 924 146 224
stroke admissions.
During the study period, IV TPA was administered in
Patient-level characteristics
12 545 ischemic stroke patients of the study cohort. (In
Age, y 74 (14.35) 75 (14.39) ⬍0.0001
addition, TPA was administered to 159 direct ED-arriving
Female 51.5% 54.6% ⬍0.0001 patients who received a final diagnosis of transient ischemic
Race-ethnicity attack.) The 12 545 TPA-treated ischemic stroke patients
White, non-Hispanic 75.4% 72.1% ⬍0.0001 represented 11.8% of all direct ED-arriving ischemic stroke
Black 13.4% 16.7% patients with documented LKWTs and 5.0% of all direct
Asian 2.3% 2.3% ED-arriving ischemic stroke patients. Among the ischemic
Arrival by emergency medical 67.2% 54.7% ⬍0.0001
stroke patients receiving IV TPA, 8111 (64.7%) arrived at
services (vs private transport) hospital within the first 60 minutes, 4327 (34.5%) between 61
NIHSS* (median, interquartile 6 (2–13) 4 (1–9) ⬍0.0001
and 180 minutes, and 107 (0.9%) ⬎180 minutes. Compared
range) with 61- to 180-minute arrivers, patients arriving in the first
History of atrial 20.2% 16.8% ⬍0.0001
60 minutes received IV thrombolytic therapy more frequently
fibrillation/flutter (27.1% vs 12.9%, unadjusted odds ratio⫽2.51; 95% CI, 2.41
Prior stroke/TIA 30.5% 31.5% ⬍0.0001
to 2.61, P⬍0.0001).
The mean DTN time across all IV TPA–treated patients
Coronary artery disease/prior 28.0% 27.4% ⬍0.0005
myocardial infarction
was 86 minutes (SD, 41.6). An inverse relation between OTD
time and DTN time was noted, with a correlation coefficient
Carotid stenosis 4.3% 4.4% ⬍0.4445
of ⫺0.30 (Figure 1). DTN time was longer among patients
Peripheral vascular disease 4.8% 5.3% ⬍0.0001
arriving in the first hour then in patients arriving in hours 1 to
Diabetes mellitus 27.5% 31.5% ⬍0.0001 3 (mean, 90.6 vs 76.7 minutes, P⬍0.0001). The distribution
History of hypertension 73.6% 74.7% ⬍0.0001 of DTN times in ⱕ1 hour–arriving patients is shown in
Smoker 17.1% 17.2% ⬍0.4879 Figure 2. Total mean elapsed time from symptom onset to
History of dyslipidemia 36.2% 34.2% ⬍0.0001 treatment in patients arriving within the first hour was 129
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IV TPA treatment 11.7% 0.5% ⬍0.0001 minutes (SD, 39). Among these early-arrival patients, 1.6%
Hospital-level characteristics
received TPA within 60 minutes of onset, 11.0% between 61
and 90 minutes, 30.2% between 91 and 120 minutes, 31.5%
Ischemic stroke/TIA
admissions/y
between 121 and 150 minutes, 21.7% between 151 and 180
minutes, and 4.0% later than 180 minutes.
301⫹ 31.2% 30.1% ⬍0.0001
The target DTN time of ⱕ60 minutes was achieved in
101–300 57.5% 57.8%
18.3% of golden hour–arriving patients. Patient characteris-
0–100 11.3% 12.2% tics in the DTN ⱕ60-minute and ⬎60-minute groups among
Hospital size (No. of beds) 375 367 ⬍0.0001 the golden hour–arriving cohort are shown in Table 4. DTN
Hospital type (nonacademic) 38.5% 39.9% ⬍0.0001 ⱕ60-minute patients were slightly younger and more often
Hospital region male compared with ⬎60-minute patients. In contrast, stroke
West 19.3% 16.7% ⬍0.0001 deficit severity, ambulance mode of ED arrival, and race did
South 35.3% 38.1%
not differ among the DTN ⱕ60-minute and ⬎60-minute
patients. The proportion of patients with a DTN time of ⱕ60
Midwest 19.7% 19.4%
minutes increased modestly over time, from 12.8% in 2003 to
Northeast 25.7% 25.9%
19.5% in 2007, with a trend showing an increase of 1.2% per
TIA indicates transient ischemic attack. Reasons for LKWT not known year. In contrast, there was no relation of achievement of
include symptom onset time not valid or not documented, hospital arrival time DTN ⱕ60 minutes to the duration of hospital participation in
not valid or not documented, symptom onset documented as after hospital
the GWTG-Stroke Program. The proportion of patients with
arrival time, or no documentation present.
*NIHSS values were recorded in 148 681 patients, 58.71% of the cohort. DTN ⱕ60 minutes nominally increased from 18.2% in year 1
to 18.9% in year 5 of GWTG-Stroke participation, with a
tics, arrival within the golden hour occurred mildly more correlation coefficient of 0.11 (P⫽0.65).
often at hospitals located in the Northeast and West. Among the 905 hospitals enrolling any patient in the
Patient and hospital factors independently associated with database during the study time period, 473 entered 5 or more
symptom OTD times ⱕ1 hour are shown in Table 3. The patients who arrived directly to the ED with an OTD time of
most powerful characteristics independently associated with ⱕ60 minutes. Among these hospitals, the proportion of
increased odds of early arrival were severe neurologic deficit, golden hour patients with a DTN time of ⱕ60 minutes was
arrival by ambulance rather than private transport, and atrial 0% to 20% at 307 hospitals (64.9%), 21% to 40% at 132
fibrillation. Patient factors associated with decreased odds of (27.9%), 41% to 60% at 30 (6.3%), 61% to 80% at 4 (0.8%),
arrival in the golden hour included older age, female sex, and and 81% to 100% at none. After dividing hospitals into
 1434 Stroke July 2010

Table 2. Patient- and Hospital-Level Characteristics of Ischemic Stroke Patients Arriving in Different
Time Windows
ⱕ60 Minutes 61–180 Minutes ⬎180 Minutes P Value
n 30 220 33 858 42 846
Patient-level characteristics
Age 71.3 (14.4) 72.0 (14.3) 70.6 (14.2) ⬍0.0001
Female 50.8% 52.2% 51.5% 0.002
Race-ethnicity
White, non-Hispanic 77.3% 77.5% 72.5% ⬍0.0001
Black 11.8% 11.9% 15.8%
Asian 2.0% 2.1% 2.7%
Arrival by emergency medical 79.0% 72.2% 55.0.% ⬍0.0001
services (vs private transport)
NIHSS* (median, interquartile range) 8 (3–16) 6 (2–12) 4 (2–9) ⬍0.0001
History of atrial fibrillation/flutter 24.3% 21.7% 16.2% ⬍0.0001
Prior stroke/TIA 30.0% 32.0% 29.6% ⬍0.0001
Coronary artery disease/prior 29.4% 28.9% 26.3% ⬍0.0001
myocardial infarction
Carotid stenosis 4.2% 4.4% 4.4% 0.57
Peripheral vascular disease 4.7% 5.0% 4.8% 0.32
Diabetes mellitus 23.4% 27.0% 30.8% ⬍0.0001
History of hypertension 71.9% 73.7% 74.9% ⬍0.0001
Smoker 84.4% 84.6% 80.6% ⬍0.0001
History of dyslipidemia 35.1% 36.5% 36.8% ⬍0.0001
Hospital-level characteristics
Ischemic stroke/TIA admissions/y
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301⫹ 29.5% 32.3% 31.6% ⬍0.0001

101–300 58.3% 56.7% 57.6%
0–100 12.2% 11.0% 10.8%
Hospital size (No. of beds) 358 380 380 ⬍0.0001
Hospital type (nonacademic) 41.0% 38.0% 37.2% ⬍0.0001
Hospital region
West 20.4% 18.4% 19.2% ⬍0.0001
South 34.2% 36.3% 35.5%
Midwest 19.3% 19.1% 20.4%
Northeast 26.1% 26.2% 24.9%
TIA indicates transient ischemic attack.
*NIHSS values were recorded in 51 378 patients, 48.1% of the cohort.

quartiles, at the 121 hospitals with the highest proportion of
golden hour patients with DTN times of ⱕ60 minutes, the
proportion of golden hour–arriving patients treated within the
first hour after arrival ranged from 27% to 80%; in the 116
hospitals of the second-quartile hospital group, the proportion
ranged from 15% to 27%; in the 118 hospitals of the third
quartile, the proportion ranged from 3% to 14%; and in the
118 hospitals of the bottom quartile, the proportion ranged
from 0% to 2%. Table 5 shows the characteristics of the
hospitals among these different performance groups. A higher
number of patients treated with IV TPA annually was the
only hospital characteristic associated with a higher propor-
tion of golden hour patients treated within 60 minutes of
arrival. Variables that were not predictive included hospital
size, total number of stroke patients encountered, academic or
nonacademic status, months of participation in the GWTG-
Stroke program, and geographic region.
Results of multivariate modeling identifying patient- and
hospital-level factors independently associated with DTN
times of ⱕ60 minutes among golden hour–arriving patients
are shown in Table 6. Greater stroke severity increased the
odds of the start of lytic treatment within 1 hour of arrival,
whereas older age, female sex, and history of diabetes or prior
stroke/transient ischemic attack decreased the odds.
Discussion
There have been several important national and multicenter
registry studies of early-arriving stroke patients,5–9 but this
study is the largest and the first to characterize in detail
ischemic stroke patients who arrive at hospital within the first
 Saver et al The “Golden Hour” in Ischemic Stroke 1435

Table 3. Patient- and Hospital-Level Characteristics Because early time of presentation is critical to early start
Independently Associated With ED Arrival Within the First 60 of therapy, a public health priority is to increase even further
Minutes of Stroke Onset the proportion of acute ischemic stroke patients presenting
Characteristic OR (95% CI) P Value within the first 60 minutes after onset.7 In the GWTG-Stroke
Severe deficit (NIHSS 9 – 41 vs 0 –3) 1.84 (1.76 –1.93) ⬍0.001
dataset, the 2 most powerful determinants of arrival in the
first 60 minutes were greater severity of stroke deficits on the
Arrival mode (emergency medical 1.78 (1.70–1.87) ⬍0.001
service vs private transportation) NIHSS and arrival by ambulance rather than private vehicle.
These findings suggest that public health messages have a
History of atrial fibrillation 1.21 (1.16–1.26) ⬍0.001
substantial opportunity to increase the proportion of early-
Moderate deficit (NIHSS 4–8 vs 0–3) 1.16 (1.10–1.22) ⬍0.001
arriving patients by educating patients, family members, and
Coronary artery disease/prior 1.08 (1.03–1.12) ⬍0.001
on-scene bystanders to recognize the symptoms of stroke and
myocardial infarction
to react to less severe as well as more severe deficits by
Prior stroke/TIA 0.96 (0.92–1.00) 0.049
calling 911 and activating the emergency medical system.
History of hypertension 0.95 (0.91–0.99) 0.018 Another factor affecting arrival in the first hour was race-
Sex (female vs male) 0.94 (0.90–0.98) 0.002 ethnicity, with blacks and Asians less likely to arrive in the
Age (per-10 y increase) 0.91 (0.90–0.92) ⬍0.001 golden hour than non-Hispanic whites. In a recent study in 13
Race-ethnicity (black 0.91 (0.86–0.97) 0.004 states and the District of Columbia, awareness of stroke
vs non-Hispanic white) warning symptoms and the importance of activating the 911
Hospital region (South vs West) 0.87 (0.78–0.98) 0.024 system was less common among black, Hispanic, and other
Moderate annual hospital stroke 0.87 (0.78–0.97) 0.012 (predominantly Asian) race-ethnic groups than among
admits (101–300 vs ⱕ100) whites.14 Several studies have found that white, non-Hispanic
Smoker 0.84 (0.80–0.88) ⬍0.001 patients with stroke are more likely to arrive at the ED in
Race-ethnicity (Asian 0.78 (0.68–0.89) ⬍0.001 early time windows and to receive thrombolytic therapy than
vs non-Hispanic white) are blacks and other race-ethnic groups.15,16 These findings
Diabetes mellitus 0.77 (0.74–0.80) ⬍0.001 suggest a need not only for general public education cam-
High annual hospital stroke admits 0.76 (0.66–0.87) ⬍0.001 paigns but also for campaigns targeted to distinctive commu-
(⬎300 vs ⱕ100) nities, including blacks, Hispanics, and Asians. Educational
OR indicates odds ratio; TIA, transient ischemic attack. Table reflects campaigns have greater effectiveness when they are tailored
to an individual’s cultural heritage.17 Targeted campaigns for
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modeling performed with 55 057 patients with full data available, including
NIHSS. No major differences (apart from NIHSS) were observed when the model
was constructed with an additional 50 962 patients without a recorded NIHSS.
60 minutes after onset, the golden hour when the opportunity
to save threatened brain tissue by reperfusion is greatest. The
sheer size of the golden hour–arriving population is a notable
finding of the investigation. Patients arriving in the first hour
of onset accounted for ⬎1 in 4 ischemic stroke patients who
presented to GWTG-Stroke hospitals with documented LK-
WTs and at least 1 in 8 of all ED-arriving ischemic stroke
patients. From recent estimates for the annual incidence of
ischemic stroke in the United States and the proportion of
ischemic patients admitted to hospital, from these findings it
may be projected that ⬎55 000 Americans each year present
to acute care hospitals within the first 60 minutes of onset of
ischemic stroke.
stroke awareness would be beneficial, by building on the
foundation of past and current initiatives, including the
American Stroke Association Power to End Stroke campaign,
the Beauty Shop Stroke Education Project, “Hip-Hop
Stroke,” and the Kids Identifying and Defeating Stroke.
Patients who arrived at the ED within the first 60 minutes
had a 2.5-fold higher rate of treatment with IV fibrinolytic
therapy than did patients arriving at 61 to 180 minutes, with
⬎1 in 4 golden hour–arriving patients receiving IV TPA.
Prior studies have indicated that, were all ischemic stroke
patients to arrive immediately at hospital after onset, about
one quarter would be appropriate candidates for IV recanali-
zation therapy, whereas three quarters would have other
contraindications to therapy, such as having mild strokes,
abnormal coagulation studies, or recent surgery.18,19 Accord-

Figure 1. Relation of OTD to DTN times

among all ischemic stroke patients
treated within 3 hours with IV TPA
(n⫽11 883). Mean⫾SD OTD time was
56.3⫾28.5 minutes and DTN time,
84.1⫾29.0 minutes. The correlation coef-
ficient was ⫺0.30.
 1436 Stroke July 2010

Figure 2. Distribution of DTN times

among patients arriving in the ED within
60 minutes after stroke onset. The
bracket shows the proportion treated
within the DTN ⱕ60-minute target.

ingly, it appears that GWTG-Stroke hospitals successfully
delivered IV fibrinolytic therapy to the great preponderance
of patients arriving in the golden hour who were fully eligible
for therapy.
However, although the proportion of golden-hour patients
treated with fibrinolytic therapy was substantial, the speed of
initiation of treatment after hospital arrival was often below
the recommended national target of a DTN time of ⱕ60
minutes. As in prior smaller studies,9 an inverse relation was
noted between time of hospital arrival and DTN time in IV
TPA–treated stroke patients. Among patients arriving 100 to
Table 4. Frequency of Patient and Hospital Characteristics
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130 minutes after onset, rapid ED care often occurred, and
DTN times ⬍60 minutes were frequently achieved, permit-
ting the start of therapy within 180 minutes. However, among
patients arriving earlier, DTN times were often extended. The
shorter DTN times in later-arriving patients in part likely
reflect a selection effect. Patients in whom the responding
team was unable to start therapy before the 3-hour mark had
elapsed did not receive treatment and therefore were not
entered into analyses of the interval from arrival to therapy
start. However, this shorter treatment time also likely reflects
a systematically more rapid diagnostic and therapeutic re-
sponse by hospital stroke teams in later-arriving patients,
when the time remaining to start therapy within the 3-hour

Among Golden Hour–Arriving Patients Treated With IV TPA <60 limit was limited. The average DTN time to therapy start in
and >60 Minutes After Arrival golden hour–arriving patients was ⬎1.5 hours, and ⬍1 in 5
patients had a DTN time meeting the national target of ⬍60
DTN Time DTN Time
minutes.
ⱕ60 Minutes ⬎60 Minutes
(n⫽1425) (n⫽6345) P Value It is important to emphasize that the national ⬍60-minute
DTN target was somewhat arbitrarily chosen, based on the
Age, y 67.6 (⫾14.7) 69.8 (⫾14.7) ⬍0.0001
opinion of a small group of experts of what was safely
Percent female 43.7% 49.9% ⬍0.0001
achievable rather than formal time-motion studies or large-
Race-ethnicity scale practice experience.4 Multiple studies have found that
White, non-Hispanic 1102 (77.3%) 4909 (77.4%) 0.2607 the target is achieved in only a minority of patients, even in
Black 152 (10.7%) 766 (12.1%) very experienced centers. It is perhaps currently best viewed
Asian 35 (2.5%) 142 (2.2%) as an ambitious target that centers should, over time, steadily
Ambulance arrival 1264 (88.7%) 5549 (87.5%) 0.1955 approach, rather than a minimum target that all centers should
NIHSS (median, 14.0 (9.0–18.0) 13.0 (8.0–19.0) 0.0461
currently meet.
interquartile range)* Nonetheless, this study identifies substantial opportunities
Calendar year
nationally for improvement in the speed of fibrinolytic
therapy initiation in acute ischemic stroke patients. Once
2003 29 (12.8%) 197 (87.2%) 0.0274
patients with ischemic stroke have done their part by arriving
2004 89 (15.9%) 472 (84.1%) at a medical center early, it is incumbent on the receiving
2005 277 (18.9%) 1191 (81.1%) hospital to perform rapid diagnostic evaluation and, in appro-
2006 479 (17.8%) 2210 (82.2%) priate patients, swiftly initiate IV fibrinolytic therapy. In
2007 551 (19.5%) 2275 (80.5%) golden hour–arriving patients, there are natural human ten-
GWTG-Stroke Year dencies to use the additional time available before the
1 427 (18.6%) 1872 (81.4%) 0.7804 outermost permitted treatment time (such as 3 or 4.5 hours) to
increase diagnostic certainty and treatment consensus. Health
2 420 (17.5%) 1975 (82.5%)
professionals are naturally tempted to use this time to elicit
3 335 (19.1%) 1417 (80.9%)
the history in greater detail, perform a fuller neurologic
4 164 (18.8%) 707 (81.2%) physical examination, carry out a detailed review of imaging
5 77 (17.8%) 355 (82.2%) and laboratory tests, discuss more fully the benefits and risks
*NIHSS values were recorded in 6043 patients, 77.8% of the cohort. of therapy with patients and on-scene family, and reach
 Saver et al The “Golden Hour” in Ischemic Stroke 1437

Table 5. Characteristics of Hospitals* With Different Rates of Achievement of DTN ⌻ime <60 Minutes Among Golden Hour,
ED-Arriving Patients
Highest Quartile Third Quartile Second Quartile Lowest Quartile P Value
Annual volume of ischemic stroke patients† 157 (⫾101) 175 (⫾130) 206 (⫾123) 153 (⫾93) 0.002
Annual volume of all IV TPA ED stroke patients 8.2 (⫾7.4) 7.8 (⫾6.2) 7.8 (⫾4.5) 4.8 (⫾6.4) ⬍0.0001
Proportion of golden hour–arriving IV TPA ED 38.6% (⫾9.8) 20.2% (⫾3.2) 9.8% (⫾3.1) 0.03% (⫾0.3) ⬍0.0001
patients with DTN time ⱕ60 min
Months in GWTG-Stroke 43.8 (⫾17.9) 47.1 (⫾18.4) 47.0 (⫾18.3) 43.8 (⫾18.8) 0.250
Hospital size 373.9 (⫾214.3) 430.7 (⫾329.0) 458.7 (⫾296.0) 354.8 (⫾185.1) 0.034
Nonacademic 43.0% 41.4% 33.1% 49.1% 0.094
Joint Commission–Certified Primary Stroke Center 69.4% 54.3% 67.0% 53.4% 0.072
Region
West 20.7% 13.8% 23.7% 14.4% 0.140
South 28.1% 37.9% 28.0% 36.4%
Midwest 20.7% 12.9% 22.9% 16.1%
Northeast 30.6% 35.3% 25.4% 33.1%
*Among 473 of the 905 hospitals with 5 or more golden hour–arriving patients in the GWTG-Stroke database. Hospitals were divided into quartiles on the basis
of the proportion of golden hour–arriving patients with an OTD ⱕ60 minutes. Quartile size and ranges are as follows: highest quartile: 121 hospitals, proportion with
DTN ⱕ60 minutes, 27– 80%; third quartile: 116 hospitals, 15–27%; second quartile: 118 hospitals, 3–14%; and lowest quartile: 118 hospitals 0 –2%.
†As measured in calendar year 2007.

primary care physicians and other off-scene advisors to arrive
at a comfortable, consensus treatment decision. Although
there are many valid reasons to delay the start of therapy in
early-arriving patients, they are all trumped by the 1, over-
whelming reason to hurry—the brain is dying all the while
that these activities are taking place.
The need to emphasize the DTN time target, rather than a
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System interventions focused on continuous, iterative qual-
ity improvement can reduce DTN times for ischemic stroke
patients. In the 2 National Institute of Neurological Disorders
and Stroke–TPA trials themselves, the median DTN time was
64 minutes, even though extensive research informed con-
sents had to be obtained in all patients.23 In regular clinical

practice, select centers worldwide have reported mean DTN

treat-before-final-time window expiration approach, has been times well ⬍60 minutes, including 25 minutes in Erlangen,
further increased by the recent demonstration that IV TPA Germany (M. Kohrmann and P. Schellinger, personal com-
can confer some modest benefit up to 4.5 hours of onset, with munication, 2010); 29 minutes in Busan, Korea24; and 38
resulting expansion of the treatment window according to minutes in Bergen, Norway.25 Successful centers report that
European, Canadian, and US national guidelines.20 –22 With- effective components of programs to accelerate DTN times
out the looming hard cutoff of the old 3-hour limit, patients include prearrival notification by emergency medical service
now arriving at hospital in the second hour after onset may be providers; written protocols for acute triage and patient flow;
at risk for the slower response and initiation of IV TPA single call systems to activate all stroke team members; CT or
observed in this study for golden-hour patients. magnetic resonance scanner clearance as soon as the center is
made aware of an incoming patient; storage and rapid access
Table 6. Patient- and Hospital-Level Characteristics to lytic drugs in the ED; collaboration in developing treat-
Independently Associated With a DTN Time <60 Minutes
ment pathways among physicians, nurses, pharmacists, and
Among Patients Arriving at the ED Within the First 60 Minutes
of Stroke Onset technologists from Emergency Medicine, Neurology, and
Radiology Departments; and continuous data collection to
Characteristic OR (95% CI) P Value drive iterative system improvement24 –26 (M. Kohrmann and
Severe deficit 2.26 (1.45–3.53) ⬍0.001 P. Schellinger, personal communication, 2010).
(NIHSS 9 – 41 vs 0 –3) Encouraging in our study were observations that achieve-
Moderate deficit 1.71 (1.07–2.74) 0.026 ment of DTN times ⬍60 minutes was highest at hospitals
(NIHSS 4 – 8 vs 0 –3) with a larger volume of IV TPA experience and a mild
Calendar year 1.12 (1.04–1.22) 0.003 temporal improving trend from 2003 to 2007. The number of
(per 1-y increase) hospitals with large volume experience is likely to increase in
Age (per-10 y increase) 0.92 (0.88–0.95) ⬍0.001 coming years owing to several factors, including the increase
Sex (female vs male) 0.85 (0.75–0.96) 0.010 to 4.5 hours in the time window for IV TPA, regionalization
Diabetes mellitus 0.79 (0.66–0.94) 0.007 of emergency stroke care with direct routing of patients to
Prior stroke/TIA 0.77 (0.65–0.91) 0.002 state-designated stroke centers,27 and the emergence into
practice of a generation of treatment-oriented neurologists
OR indicates odds ratio; TIA, transient ischemic attack. Table reflects
modeling performed with 6043 patients with full data available, including and emergency physicians. The finding that the length of time
NIHSS. No major differences (apart from NIHSS) were observed when the model in the GWTG-Stroke program was not associated with an
was constructed with an additional 1727 patients without a recorded NIHSS. increase in the proportion of patients treated within 60
 1438 Stroke July 2010
minutes of arrival suggests a need to revisit and reframe
aspects of the GWTG-Stroke toolkit and intervention strategy
to highlight the importance of this target and provide concrete
strategies for its achievement in various practice settings.
This study has several limitations. Hospitals participating
in GWTG-Stroke are likely to have more well-organized
stroke systems of care than do nonparticipating hospitals, so
other US hospitals are likely, on average, to have worse lytic
treatment rates and DTN times than observed in this cohort.
Nonetheless, by the final year of observation, ⬇23% of US
hospitals containing ⬇41% of licensed US hospital beds were
participating in GWTG-Stroke, so this study does reflect a
substantial proportion of US practice. The LKWT was
documented in 42% of patients. Although this rate is higher
than in many epidemiologic studies (in which LKWT is often
documented only 15% to 30% of the time), it is lower than
desirable. However, is likely that the LKWT is more often
documented among early-arriving patients, in whom it greatly
influences ED management, and less often documented
among late-arriving patients, in whom the exact onset time is
of less practical importance. In accord with this hypothesis,
patients with documented LKWTs more often arrived by
emergency medical service ambulance and had greater stroke
severity, 2 features associated with earlier arrival. Conse-
quently, the analyses in this study confined to the golden
hour–arriving patients likely capture the great preponderance
of actual golden hour–arriving patients in the study period.
During the study period, a small group of treated patients
received a final diagnosis of transient ischemic attack, ac-
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counting for 1.3% of IV TPA–treated patients. It may be
suggested that the diagnosis in these patients should be
reclassified as therapeutically averted strokes and included in
the ischemic stroke group. We retained the original GWTG-
Stroke database diagnostic categories, so our time to treat-
ment analysis was performed in the 98.7% of IV TPA–treated
patients who received a final diagnosis of ischemic stroke.
Residual measured and unmeasured confounding variables
may have influenced some of the findings.
We investigated the influence of multiple patient- and
hospital-level factors on care of early-arriving patients. How-
ever, many additional factors important in fostering rapid care
were not captured in the GWTG-Stroke database and there-
fore not analyzed, including pre-arrival notification policies
of local emergency medical service agencies, hospital provi-
sion of education programs to emergency medical services,
existence of a regional stroke system of care with routing of
stroke patients directly to designated stroke centers, location
of CT or magnetic resonance imaging scanners in the ED, and
policies regarding need for ancillary testing before treatment,
such as coagulation studies, CT angiography, and CT perfu-
sion imaging or multimodal magnetic resonance imaging.
Data quality is always a concern in registry studies, and the
GWTG-Stroke registry is implemented by a diverse group of
users. To optimize data quality, the GWTG-Stroke program
includes detailed training of site chart abstractors, standard-
ized case definitions and coding instructions, predefined logic
and range checks on data fields at data entry, audit trails, and
regular data quality reports for all sites. Limited source
documentation audits at the individual state and site level
have shown high data quality, and a nationally representative
audit is under way. Nevertheless, as in any cardiovascular and
stroke registry, data are subject to limitations in the quality
and accuracy of the medical records themselves, as well as to
the quality of medical record abstraction. Furthermore, there
is a portion of ischemic stroke patients for whom onset time
is unavailable, not due to limitations in data quality but
because the time of onset cannot be obtained from the patient.
We conclude that golden hour–arriving patients are a
substantial population, accounting for at least 1 in 8 ischemic
stroke patients who arrive directly to the ED. Arrival by
ambulance rather than private vehicle was among the most
powerful determinants of arrival in the golden hour. On
arrival, they receive thrombolytic therapy more frequently
and earlier than do late arrivers. Although target DTN times
ⱕ60 minutes are achieved in fewer than one fifth of golden
hour–arriving patients, treatment times show a mild improv-
ing national trend over time and are better at high treatment
volume centers. These findings support sustained public
education efforts to increase the proportion of patients arriv-
ing within the first 30 to 60 minutes after stroke onset by
emphasizing the recognition of stroke symptoms and the
immediate activation of 911. These data also encourage
reinvigorated hospital performance improvement activities to
shorten DTN times in patients who present in the golden
hour, when the volume of salvageable brain and the patient’s
capacity to benefit from reperfusion therapy are greatest.
Sources of Funding
GWTG-Stroke is funded by the American Heart Association and the
American Stroke Association. The program is also supported in part
by unrestricted educational grants to the American Heart Association
by Pfizer, Inc, New York, NY, and the Merck-Schering Plough
Partnership (North Wales, Pa), who did not participate in the design,
analysis, manuscript preparation, or approval. J.L.S. was supported
for this work by an American Heart Association PRT Outcomes
Research Center Award and by NIH-NINDS Awards P50 NS044378
and U01 NS 44364.
Disclosures
Dr Saver serves as a member of the GWTG Science Subcommittee
and as a scientific consultant regarding trial design and conduct to
CoAxia, Concentric Medical, Talecris, and Ev3 (all modest); re-
ceived lecture honoraria from Ferrer and Boehringer Ingelheim
(modest); was an unpaid investigator in a multicenter prevention trial
sponsored by Boehringer Ingelheim; has declined consulting/hono-
raria monies from Genentech since 2002; and is an employee of the
University of California, which holds a patent on retriever devices
for stroke. Dr Smith receives research support from the NIH (NINDS
R01 NS062028), the Canadian Stroke Network, the Hotchkiss Brain
Institute, and Canadian Institutes for Health Research and receives
salary support from the Canadian Institutes for Health Research. Dr
Fonarow receives research support from the NIH (significant); serves
as a consultant to Pfizer, Merck, Schering Plough, Bristol Myers
Squibb, and Sanofi-Aventis (all modest); receives speaker honoraria
from Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and
Sanofi-Aventis (all significant); and is an employee of the University
of California, which holds a patent on retriever devices for stroke. Dr
Reeves receives salary support from the Michigan Stroke Registry.
Dr Zhao is a member of the Duke Clinical Research Institute, which
serves as the American Heart Association GWTG data coordinating
center. Dr Olson is a member of the Duke Clinical Research Institute,
which serves as the American Heart Association GWTG data
coordinating center. Dr Schwamm serves as a consultant to the
 Saver et al
Research Triangle Institute, CryoCath, and the Massachusetts De-
partment of Public Health.
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