Saver et al. Epub June 3, 2010 STROKE The Golden Hour and Acute Brain Ischemia: Presenting Features...

Saver et al. Epub June 3, 2010 STROKE

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


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


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


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


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


Objective

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


MethodsData 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


MethodsStudy 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”


MethodsCase 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


MethodsCharacteristics

• Patient Data included:– Demographics– Medical history– Initial head computerized tomography findings– In-hospital treatment and events– Discharge treatment– Mortality– Discharge destination


MethodsCharacteristics

• Hospital level data included:– Bed size– Academic or non-academic status– Annual volume of stroke discharges– Geographical region


MethodsData 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


ResultsAnalysis 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.


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) < 0.0001

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%

< 0.0001

< 0.0001

Arrival by ambulance 79.0% 72.2% 55.0.% < 0.0001

NIHSS (median, IQR) 8 (3-16) 6 (2-12) 4 (2-9) < 0.0001


Characteristic OR (95% CI) P valueSevere deficit (NIHSS 9-41 vs 0-3) 1.84 (1.76-1.93) <0.001

Arrival mode (EMS vs Private transportation 1.78 (1.70-1.87) <0.001H/o atrial fibrillation 1.21 (1.16-1.26) <0.001

Moderate deficit (NIHSS 4-8 vs 0-3) 1.16 (1.10-1.22) <0.001CAD/prior MI 1.08 (1.03-1.12) <0.001

Prior stroke/TIA 0.96 (0.92-1.00) 0.049H/o HTN 0.95 (0.91-0.99) 0.018

Sex (F vs M) 0.94 (0.90-0.98) 0.002Age (per 10 year increase) 0.91 (0.90-0.92) <0.001

Race-ethnicity, Black vs White, non-Hispanic 0.91 (0.86-0.97 0.004Hospital Region (South vs West) 0.87 (0.78-0.98) 0.024

Moderate annual hospital stroke admits (101-300 vs ≤100) 0.87 (0.78-0.97) 0.012Smoker 0.84 (0.80-0.88) <0.001

Race-ethnicity, Asian vs White, non-Hispanic 0.78 (0.68-0.89) <0.001Diabetes Mellitus 0.77 (0.74-0.80) <0.001

High annual hospital stroke admits (>300 vs ≤100) 0.76 (0.66-0.87) <0.001

Patient and Hospital Level Characteristics Independently Associated with ED Arrival within the First 60 Minutes of Onset


ResultPatient 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


• 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%

61-180 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)

ResultsOnset-to-Door Time


ResultsTime 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


ResultsSymptom 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


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


• Mean OTD 56.3 mins, DTN 84.1mins

• IV TPA more frequent among golden hour patients than 1-3 hour27.1% vs 12.9%, p < 0.0001

Onset to Door Times Among IV TPA Patients

N Percent

< 60 mins 8111 64.7%

61-180 mins 4327 34.5%

> 180 mins 107 0.9%

Results


Results: IV TPA DTN Times

0

20

40

60

80

100

120

140

160

180

200

0 20 40 60 80 100 120 140 160 180 200

OTD

DT

N

• 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 < 0.0001

• Inverse relation OTD – DTN times: r = - 0.30


ResultsDTN Time among Golden Hour Patients


ResultsTarget 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%


ResultsTarget 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%


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.


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.

Saver et al. Epub June 3, 2010 STROKE The Golden Hour and Acute Brain Ischemia: Presenting Features...

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