Characteristics, Performance Measures, and In-Hospital Outcomes of the First One Million Stroke and Transient Ischemic Attack Admissions in Get With The Guidelines-Stroke Gregg C. Fonarow, MD; Mathew J. Reeves, PhD; Eric E. Smith, MD, MPH; Jeffrey L. Saver MD; Xin Zhao, MS; DaWai Olson, PhD, RN; Adrian Hernandez, MD, MHS; Eric D. Peterson, MD, MPH; Lee H. Schwamm, MD on behalf of the Get With The Guidelines Steering Committee and Hospitals Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Disclosures GWTG-Stroke is sponsored by the AHA/ASA and is also supported in part by an unrestricted educational grant from Merck/Schering- Plough Pharmaceutical. The individual author disclosure are listed in the manuscript Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Stroke results in substantial morbidity and mortality. While evidence-based guidelines for stroke and TIA care have been developed along with improved diagnostic and treatment modalities, there are gaps, variations, and disparities in how these are applied. Furthermore many hospitals may not have the systems, organization, staff, and equipment to effectively diagnose, manage, and treat acute stroke patients. Background Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

The Get With The Guidelines (GWTG)-Stroke Program was developed by the AHA/ASA as a national stroke registry and performance improvement program with the primary goal of improving the quality of care and outcomes for stroke and TIA as well as serve as a scientific resource for new information. Although several prior studies have described the quality of care and outcomes for patients hospitalized with stroke and TIA, uncertainty remains about care quality and clinical outcomes for contemporary populations of patients hospitalized with stroke and TIA. Furthermore, little is known regarding temporal trends and whether there have been improvement in clinical outcomes among hospitals participating in GWTG-Stroke. Background Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

The objectives of this study were to analyze the characteristics, performance measures, in-hospital outcomes, and temporal trends in the first 1,000,000 acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and TIA admissions from 1,392 hospitals that participated in the GWTG-Stroke Program from 2003 to Objectives Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

GWTG Stroke is an ongoing, voluntary, observational registry and a continuous performance improvement program for patients hospitalized with stroke or TIA. A web-based Patient Management Tool provides decision support at the point-of-care, on-demand reporting and patient education features (Outcome, Cambridge, MA). Patient data were abstracted by trained hospital personnel. These included demographics, medical history, initial CT findings, in-hospital treatment and events, discharge treatments, treatment contraindications, counseling, in-hospital mortality, and discharge destination. Methods Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Trained hospital personnel ascertained consecutive patients admitted with acute ischemic stroke by either prospective clinical identification, retrospective identification using ICD-9 discharge codes, or a combination. Methods used for prospective identification varied, but included regular surveillance of ED records, ward census logs, and/or neurological consultations. The eligibility of each acute stroke or TIA admission was confirmed at chart review prior to abstraction. Performance and quality measures were collected and reported. Outcomes included: % of pts with a short length of stay (LOS <4 days); % discharged home, and in-hospital mortality. Methods Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Characteristics, performance measures, in-hospital outcomes, and temporal trends were evaluated. P-values were based on chi-square rank based group means score statistics for all categorical row variables (equivalent to Wilcoxon test for two levels). GEE multivariable logistic regression models were developed to quantify how performance measures, in-hospital mortality, discharge home, and LOS changed on a continuous basis by quarter from 2003 to 2009 and reported as cumulative change over 6 years adjusting for patient and hospital variables. Since the makeup of participating hospitals may have changed over time in GWTG-Stroke, we also performed a separate set of analyses for temporal trends among core hospitals which were participating by 2004 and contributed cases in all subsequent quarters of the study. Statistical Methods Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

From April 1 st 2003 to August 24 th 2009, there were 1,000,000 patients with stroke or TIA entered from 1392 GWTG-Stroke participating hospitals. There were 601,599 (60.2%) ischemic strokes, 108,671 (10.9%) intracerebral hemorrhage s, 34,945 (3.5%) subarachnoid hemorrhages, 26,977 (2.7%) strokes not classified, and 227,788 (22.8%) TIAs. Stroke and TIA patients enrolled by year 2003 N= 18,971 (starting April 1 st 2003) 2004 N= 41, N= 96, N= 167, N= 220, N= 262, N= 159,083 (through August 24 th, 2009) Results Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Enrollment in GWTG-Stroke by Quarter Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Hospital Participation in GWTG-Stroke by State N=1392 Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Hospital Characteristics 1392 GWTG-Stroke Participating Hospitals CharacteristicN or % Number of Stroke Discharges Number of BedsMedian (IQR)369 ( ) RegionNortheast25.9 Midwest19.0 South37.7 West17.3 Hospital TypeAcademic60.5 Non Academic39.5 Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Hospitals in every state participate in the GWTG-Stroke Program. Of participating hospitals, 39.5% were non-academic institutions. Divided by regions, the South has the largest number of participating hospitals (n=500), followed by the Northeast (n=346), the Midwest (n=325), and the West (n=252). GWTG-Stroke participating hospitals account for an estimated 32.3% of US acute care hospitals. In 2008, there were 156,000 ischemic stroke patients entered into GWTG-Stroke out of 663,000 expected in the US (25%) and 47,937 hemorrhagic stroke patients entered out of 117,000 expected in the US (41%). Hospital Participation in GWTG-Stroke Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

VariableLevelTotal NOverall AgeMedian Years (IQR) (60-82) GenderFemale Race/EthnicityWhite Black Asian Hispanic Arrival ModeEMS Private transport Time to Symptom Onset to Arrival Median Minutes (IQR) (60-384) NIH Stroke Scale*Median (IQR) (1-10) Medical History Atrial Fib/FlutterYes Stroke/TIAYes CAD/Prior MIYes Diabetes MellitusYes PVDYes HypertensionYes SmokerYes DyslipidemiaYes Patient Characteristics Total Cohort Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

VariableLevelIschemic Stroke Subarachnoid Hemorrhage Intracerebral Hemorrhage Stroke, Not Classified TIAP-value N (%) (60.2%) (3.5%) (10.9%) (2.7%) (22.8%) Demographic AgeMedian Years < th -75th GenderFemale <.0001 Race/EthnicityWhite <.0001 Black Asian Hispanic Arrival Modefrom scene <.0001 Private transport Time to Symptom Onset to Arrival Median Minutes 25 th -75th <.0001 NIH Stroke Scale* Median < th -75th Patient Characteristics by Event Type Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

VariableIschemic Stroke Subarachnoid Hemorrhage Intracerebral Hemorrhage Stroke, Not Classified TIAP-value Total (60.2%) (3.5%) (10.9%) (2.7%) (22.8%) Medical History Atrial Fib/Flutter <.0001 Stroke/TIA <.0001 CAD/Prior MI <.0001 Carotid Stenosis <.0001 Diabetes Mellitus <.0001 PVD <.0001 Hypertension <.0001 Smoker <.0001 Dyslipidemia <.0001 Patient Characteristics by Event Type Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

For the 1,000,000 acute stroke (n=772,212) and TIA (n=227,788) admissions entered into the program, the mean age was 70.1 ± 14.9 years and over half (53.5%) were women. IS and TIA patients were older, more likely to be men, less likely to be smokers, and more likely to have medical co-morbidities than ICH and SAH patients. ICH patients had a relatively high prevalence of vascular risk factors, but not as high as for IS or TIA patients. Patients with stroke not classified were most similar to IS patients. SAH patients were more likely than IS or TIA patients to be younger, female, non-white and to be cared for in larger academic hospitals. Patient Characteristics in GWTG-Stroke Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Performance MeasureISSAHICHSNCTIAP-value* Acute PM IV rt-PA 2 Hour NA. Early Antithrombotics 95.08NA 95.86<.0001 DVT Prophylaxis NA<.0001 Discharge PM Antithrombotics NA 95.15<.0001 Anticoag for AF NA 89.11< or ND NA 72.35<.0001 Smoking Cessation <.0001 Summary PM All-or-None Measure <.0001 Composite Measure <.0001 Performance Measures by Event Type Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Quality MeasuresISSAHICHSNCTIAP-value* Door to CT ≤25 Minutes <.0001 Dysphagia Screen NA<.0001 Stroke Education† <.0001 Rehabilitation † NA<.0001 Quality Measures by Event Type †Data collected starting 2008 Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Temporal Trends in Acute Stroke and TIA Care Temporal trend P value is < for each measure Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Measures N P-value All-or-None Measure Overall <.0001 IS <.0001 SAH <.0001 ICH <.0001 SNC <.0001 TIA <.0001 Composite Measure Overall <.0001 IS <.0001 SAH <.0001 ICH <.0001 SNC <.0001 TIA <.0001 Temporal Trends in Acute Stroke and TIA Care Summary Performance Measures Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Unadjusted (2003 to 2009)Adjusted (2003 to 2009) * OutcomeCategoryORLower (95% CI) Upper (95% CI) P- value ORLower (95% CI) Upper (95% CI) P-value All-or-NoneOverall < <.001 MeasureIS < <.001 SAH < <.001 ICH < <.001 SNC < <.001 TIA < <.001 Temporal Trends in Acute Stroke and TIA Care *Adjusted for age, gender, race, medical history of Afib, stroke/TIA, CAD/prior MI, carotid stenosis, diabetes, PVD, hypertension, dyslipidemia, smoking, arrival mode (EMS vs. other), on/off hour presentation (7 am-6 pm MF vs other), hospital characteristics of region, number of beds, annual stroke volume, academic vs. not. Overall cohort also adjusted for stroke type (IS, SNC, SAH, ICH, TIA). Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22 All-or-None Performance Measure

In each successive year there were clinically meaningful and statistically significant improvements in all 7 individual PM. The absolute improvement from 2003 to 2009 ranged from +4.3% for discharge antithrombotics to +51.0% for smoking cessation (P <.0001 for all comparisons). IV tPA use in eligible patients increased from 29.7% to 71.6% (+41.9%), P< There was substantial and significant improvement in the all-or-none care measure from 2003 to 2009, 44.0% to 84.3% (+40.3%), P< overall and for each cerebrovascular event type. There was also an increase in composite care from 72.3% to 93.1% (+20.8%), P< overall and for each event type. Performance Measures in GWTG-Stroke Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

VariableLevel OverallIschemic Stroke Subarachnoi d Hemorrhage Intracerebral Hemorrhage Stroke, Not Classified TIAP-value Total Admissions 1,000,000601,599 (60.2%) 34,945 (3.5%) 108,671 (10.9%) 26,977 (2.7%) 227,788 (22.8%) Discharge Status Died Discharge Destination <.0001 Home <.0001 Skilled Nursing Facility Rehabilitation Hospice Transfer Left AMA/Other AmbulatoryIndependent <.0001 StatusWith Assistance Unable Not Documented Length of StayMedian < th -75th Mean >4 Days <.0001 Stroke-Related In-Hospital Outcomes by Cerebrovascular Event Type Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

UnadjustedAdjusted + OutcomeEvent Type (vs. IS) ORLower (95% CI) Upper (95% CI) P-valueORLower (95% CI) Upper (95% CI) P-value In-HospitalSAH < <.001 MortalityICH < <.001 SNC TIA < <.001 DischargeSAH <.001 HomeICH < <.001 SNC < <.001 TIA < <.001 LOS (> 4 days)SAH < <.001 ICH < <.001 SNC < <.001 TIA < <.001 Clinical Outcomes by Cerebrovascular Event Type Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22 + Adjusted for patient and hospital characteristics. See manuscript for variables

SAH and ICH patients had substantially higher in-hospital mortality rates, were less likely to be discharged home, and were more likely to be discharged to a SNF or hospice compared to IS patients. As expected, in-hospital mortality was very low in patients hospitalized with TIA (0.3%). Adjustment for potential confounding variables and clustering of data within hospitals did little to attenuate the cerebrovascular event type related differences for clinical outcomes. The adjusted OR for in-hospital mortality for ICH compared to IS was 5.8; for SAH it was 5.4. After adjustment the odds of being hospitalized longer than 4 days remained significantly elevated for SAH and ICH compared to IS. Clinical Outcomes in GWTG-Stroke Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Temporal Trends in Mortality Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22 Temporal trend P value for ischemic stroke (P<0.0001), intracerebral hemorrhage (P=0.0036), subarachnoid hemorrhage (P=0.0106), transient ischemic attack (P=0.2091).

Variable (%) P-value Discharge Home Overall <.0001 IS <.0001 SAH ICH SNC TIA LOS > 4 Overall <.0001 IS <.0001 SAH <.0001 ICH <.0001 SNC TIA <.0001 Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22 Temporal Trends in Clinical Outcomes

Unadjusted (2003 to 2009)Adjusted (2003 to 2009) * OutcomeCategoryORLower (95% CI) Upper (95% CI) P- value ORLower (95% CI) Upper (95% CI) P-value In-HospitalOverall < MortalityIS < SAH ICH SNC < TIA DischargeOverall < HomeIS < SAH ICH <.001 SNC TIA LOSOverall < <.001 (> 4 days)IS < <.001 SAH ICH SNC TIA < <.001 Temporal Trends in Clinical Outcomes * Adjusted for patient and hospital characteristics. Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Clinical Outcomes by Calendar Year for Ischemic Stroke Patients Outcome 2003 (12,549) 2004 (26,252) 2005 (60,414) 2006 (102,282) 2007 (131,891) 2008 (159,825) 2009 (108,386) P value Mortality <.001 Discharge Home <.001 LOS (> 4 days) <.001 Total Ischemic Stroke Patients N = 601,599 Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

UnadjustedAdjusted+ OutcomeOR95 CI P valueOR95. CI95 CIP value Mortality < Discharge Home < LOS (> 4 days) < <.001 Temporal Trends in Outcomes for Ischemic Stroke +Adjusted for PATIENT CHARACTERISTICS of age, gender, race, medical history of atrial fibrillation, previous stroke/TIA, coronary artery disease, carotid stenosis, diabetes, peripheral vascular disease, hypertension, dyslipidemia, smoking, arrival mode (EMS vs. other), on/off hour presentation (7 am-6 pm M-F vs. other), and HOSPITAL CHARACTERISTICS of region, number of beds, annual stroke volume, and teaching hospital vs. not. Odd Ratios for 6 Year Change 2003 to 2009 Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

There were temporal trends for improvement in clinical outcomes from 2003 to The portion of patients discharged home in 2003 was 53.8% compared to 57.1% in 2009 (P 4 days was seen in 40.1% in 2003 compared to 35.6% in After adjustment, the portion of patients with hospital LOS >4 days declined significantly, adjusted OR 0.72, 95% CI , P< In-hospital mortality also declined significantly over time, unadjusted OR 0.87, 95% CI , P<0.001, 2003 to 2009, but after risk adjustment was only significant for ischemic stroke and TIA. There was a 10% risk adjusted reduced odds of mortality in patients with IS from 2003 to Temporal Trends in Clinical Outcomes Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Data were collected by medical chart review and are dependent upon the accuracy of documentation and abstraction. Residual measured and unmeasured confounding variables may have influenced the findings. Further study will be needed to determine if these improvements in outcomes are due to improved care (faster in-hospital response times, guideline-adherence, and reduced complications or errors), secular trends, or other reasons. These findings may not apply to hospitals that differ in patient characteristics or care patterns from GWTG-Stroke Hospitals. Limitations Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

GWTG-Stroke is the largest registry and performance improvement programs for hospitalized stroke and TIA patients, with data from 1,000,000 admissions including more than 600,000 IS, 100,000 ICH, 30,000 SAH, and 225,000 TIA admissions. This study has characterized the demographics, performance measures, and in-hospital clinical outcomes in a very broad cohort of acute stroke and TIA hospitalizations from every state in the country. Among GWTG-Stroke participating hospitals there were substantial improvements over time in performance measures, overall and for each cerebrovascular event type. Composite care performance increased substantially from 72.3% to 93.1% (+20.8%) from 2003 to Conclusions Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

Among hospitals participating in GWTG-Stroke, there have been reductions in LOS and mortality at discharge over the past 6 years in the patients with acute ischemic stroke. These findings persist after adjustment for patient and hospital characteristics. Further research is warranted to determine if these reductions in mortality are due to increased adherence to inpatient care process measures, secular trends, unmeasured confounders, or other reasons. Other factors might include increased public education and awareness, increased use of EMS, improvements in in-hospital response times, guideline-adherence, and prevention of complications or medical errors. Conclusions Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22

This study demonstrates the ongoing value of GWTG-Stroke as an integrated stroke and TIA national registry providing national surveillance, supporting vigorous efforts to improve evidence-based stroke/TIA care, and fostering innovative research. Conclusions Fonarow GC et al. Circ Cardiovasc Qual Outcomes epub Feb 22