1. The Golden Hour and Acute Brain Ischemia: Presenting Features and Lytic Therapy in Over 30,000 Patients Arriving within 60 Minutes of Onset at GWTG-S Hospitals
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

2. Disclosures
The Get With The Guidelines®–Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Bristol-Myers Squib/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck.
The individual author disclosures are listed in the manuscript

3. Background
The benefit of intravenous thrombolytic therapy in acute brain ischemia is strongly time dependent
Therapeutic yield is maximal in the first minutes after symptom onset and declines steadily during the first 3 hours

4. Background
The Joint Commission target for Primary Stroke Centers is to achieve a Door-to-Needle time of within 60 minutes in 80% of patients
Hospitals participating in the Get With The Guidelines®–Stroke Quality Improvement program have been shown to successfully deliver intravenous fibrinolytic therapy to patients arriving within the first 60 minutes of onset

5. Introduction
The benefit of intravenous thrombolytic therapy in acute brain ischemia is strongly time dependent. Therapeutic yield is maximal in the first minutes after symptom onset and declines rapidly over the next 4.5 hours.
In the typical large artery ischemic stroke, in each minute in which reperfusion is delayed, 2 million nerve cells die.
Patients receiving treatment within the first 60 minutes (the “Golden Hour”) of onset of symptoms, have the greatest opportunity to benefit from recanalization therapy
Hyperacute-arriving patients and their treatment have not previously not been well characterized

6. Objective
To examine the frequency, characteristics and treatment of Ischemic Stroke patients arriving at hospitals within the “Golden Hour”

7. Methods Data Source
Hospitals participating in GWTG-Stroke who utilize the web-based patient management tool for data collection
Outcome Sciences, Inc. served as the data collection and coordination center
The Duke Clinical Research Institute (DCRI) served as the data analysis center

8. Methods Study Population
Between April 1, 2003 to December 31, 2007
905 GWTG-Stroke Hospitals
431,170 Ischemic Stroke and TIA patients arriving to Hospital Emergency Departments (ED’s) within 60 minutes of “last known well time”

9. Methods Case Identification
Trained hospital personnel instructed to ascertain consecutive Acute Stoke Admissions
Methods included regular surveillance of Emergency Dept. records, ward census logs and/or neurological consultations
The eligibility of each acute stroke admission was confirmed at chart review prior to abstraction

10. Methods Characteristics
Patient Data included:
Demographics
Medical history
Initial head computerized tomography findings
In-hospital treatment and events
Discharge treatment
Mortality
Discharge destination

11. Methods Characteristics
Hospital level data included:
Bed size
Academic or non-academic status
Annual volume of stroke discharges
Geographical region

12. Methods Data Analyzed
Contingency tables were developed to assess differences in:
Demographics (age, sex)
Stroke severity
Arrival Mode (ambulance, private vehicle)
Door-to-Needle (DTN) Time
Door-to-Imaging (DTI) Time
Outcome Destination at Discharge
Generalized estimating equations logistics regression models, accounting for in-hospital clustering, were generated to identify independent predictors of Onset-to-Door Time (OTD) and Door-to-Needle Time (DTN) < 60 minutes

13. Results Analysis Sample
During the 4.75 year time period, at 905 hospital sites, data for 431,170 Ischemic Stroke and TIA patients were entered into the GWTG-Stroke database.
Main analysis performed upon 106,924 patients in this cohort with Ischemic Stroke, a documented last known well-time and presentation directly to the Emergency Department by ambulance or private vehicle.

14. Results - Patient Characteristics
≤ 1 Hr
1-3 Hrs
> 3 Hrs
P value
Age (SD)
71.5 (14.6)
72.1 (14.3)
70.6 (14.2)
<
Sex (Female)
50.8%
52.2%
51.5%
0.002
White, Non-Hispanic
Black
77.3%
11.8%
77.5%
11.9%
72.5%
15.8%
Arrival by ambulance
79.0%
72.2%
55.0.%
NIHSS (median, IQR)
8 (3-16)
6 (2-12)
4 (2-9)

15. Patient and Hospital Level Characteristics Independently Associated with ED Arrival within the First 60 Minutes of Onset
Characteristic
OR (95% CI)
P value
Severe deficit (NIHSS 9-41 vs 0-3)
1.84 ( )
<0.001
Arrival mode (EMS vs Private transportation
1.78 ( )
H/o atrial fibrillation
1.21 ( )
Moderate deficit (NIHSS 4-8 vs 0-3)
1.16 ( )
CAD/prior MI
1.08 ( )
Prior stroke/TIA
0.96 ( )
0.049
H/o HTN
0.95 ( )
0.018
Sex (F vs M)
0.94 ( )
0.002
Age (per 10 year increase)
0.91 ( )
Race-ethnicity, Black vs White, non-Hispanic
0.91 (
0.004
Hospital Region (South vs West)
0.87 ( )
0.024
Moderate annual hospital stroke admits ( vs ≤100)
0.87 ( )
0.012
Smoker
0.84 ( )
Race-ethnicity, Asian vs White, non-Hispanic
0.78 ( )
Diabetes Mellitus
0.77 ( )
High annual hospital stroke admits (>300 vs ≤100)
0.76 ( )

16. Result Patient Characteristics
Patients with documented “Last Known Well Time”, saw a:
Higher arrival by EMS
Higher use of TPA
Higher Stroke Severity
Lower frequency of Blacks

17. Results Onset-to-Door Time
106,924 ischemic stroke patients arrived directly to GWTG-S hospital EDs by ambulance or private vehicle
Onset to Door Times N
Percent
< 60 mins
30,220
28.3%
mins
33,858
31.7%
> 180 mins
42,846
40.1%
Among < 60 mins patients, mean onset to door (OTD) time: 39.9 mins (SD 14.8)

18. Results Time Of Arrival cohorts
Race/Ethnicity
Slightly more often were non-Hispanic white in both 1 hour or under and 1-3 hour arrival
Less often Black or Asian in same time frames
Stroke Severity
Greatest among Golden Hour arriving patients
Intermediate among 1-3 hour arriving patients
Least among beyond 3 hour arriving patients
Frequency of Arrival to Hospital by Ambulance
79% in 1 hour or under patients
72.2% in 1-3 hour patients
55% in beyond 3 hour patients
All above groups similar in age and gender
Arrival occurred mildly more often at hospitals located in the Northeast and West

19. Results Symptom Onset-to-Door Time
Patient and Hospital Factors independently associated with Symptom OTD Time less than or equal to 1 hour (Golden Hour)
Increased odds of early arrival
Severe neurologic deficit
Arrival by ambulance rather than private transport
Atrial Fibrillation
Decreased odds of early arrival
Hospital location in the South
Higher annual number of Stroke Admissions

20. Results IV TPA given to: 12,545 direct ED IS patients
159 direct ED aborted IS patients (TPA-induced TIA)
11.8% of all direct ED, IS patients with documented OTD
5.0% of all direct ED IS patients

21. Onset to Door Times Among IV TPA Patients
Results
Mean OTD 56.3 mins, DTN 84.1mins
IV TPA more frequent among golden hour patients than 1-3 hour
27.1% vs 12.9%, p <
Onset to Door Times Among IV TPA Patients N
Percent
< 60 mins
8111
64.7%
mins
4327
34.5%
> 180 mins
107
0.9%

22. Results: IV TPA DTN Times
DTN in all 12,545 IV TPA patients: 86 mins (SD 42)
Longer DTN in golden hr patients: mean 90.6 v 76.7 mins, p <
Inverse relation OTD – DTN times: r =

23. Results DTN Time among Golden Hour Patients

24. Results Target DTN Time ≤ 60 Minutes
Target DTN ≤ 60 mins achieved in 18.3% of golden hour-arriving patients
Modest increase in proportion of patients with target DTN times by calendar year
Absolute increase 1.2% per year, p=.027
Year
Proportion with DTN ≤ 60 mins
2003
12.8%
2004
15.9%
2005
18.9%
2006
17.8%
2007
19.5%

25. Results Target DTN Time ≤ 60 Minutes
No substantial increase in proportion of patients with target DTN times duration of hospital participation in GWTG-S
p = 0.65
Year Participating in GWTG-S
Proportion with DTN ≤ 60 mins 1
18.0% 2
18.5% 3
18.4% 4
19.0% 5
18.9%

26. Limitations
Participation in GWTG is voluntary and may select for higher performing hospitals.
Hospitals participating in GWTG-Stroke are likely to have more well-organized stroke systems of care than nonparticipating hospitals, so other US hospitals are likely on average to have worse lytic treatment rates and door to needle times than observed in this cohort.
The last known well time was documented in 42% of patients.
Additional factors important in fostering rapid care were not captured in the GWTG-Stroke database and therefore not analyzed, including policies of local Emergency Medical Service (EMS) agencies, hospital provision of education programs to EMS, location of CT or MRI scanners in the ED, and policies regarding need for ancillary testing before treatment such as coagulation studies, CT angiography and CT perfusion imaging, or multimodal MRI imaging, etc.

27. Conclusions
At GWTG-S hospital ED’s, these patients arrive within 1 hour of onset symptoms:
More than 1/4 of patients with documented Onset Time
At least 1/8 of all Ischemic Stroke patients
These Golden Hour patients:
receive thrombolytic therapy more frequently but more slowly than late arrivers.
Target Door-To-Needle Time of less than 60 minutes achieved in less than 1/5 of these patients
The findings support public health initiatives to increase early presentation and shorten Door-to-Needle times in patients arriving within the Golden Hour.