1. Delays in Fibrinolytic Administration for Acute ST-Segment Elevation Myocardial Infarction: Results from the Acute Coronary Treatment and Interventions Outcomes Network Registry – Get With the Guidelines (ACTION Registry ® -GWTG TM ) Seth Glickman, MD 1 ; Charles Cairns, MD 1 ; Anita Chen, MS 2 ; Christopher Granger, MD 2 ; Christopher Cannon, MD 3 ; Elizabeth Fraulo, MS 2 ; Eric Peterson, MD, MPH 2, Matthew Roe, MD 2 1. Department of Emergency Medicine, University of North Carolina- Chapel Hill 2. Duke University Medical Center, Durham, NC 3. Brigham and Women’s Hospital, Boston, MA,

2. Disclosures Robert Wood Johnson Foundation Physician Faculty Scholar Award (Glickman PI) American Heart Association PRT Outcomes Research Center Project Grant (Glickman, Granger, Co PIs) NCDR-American College of Cardiology

3. Background Reperfusion therapy STEMI reduces mortality in a time-dependent manner –PCI –Fibrinolytic therapy 2007 AHA/ACC STEMI Guidelines –“STEMI patients presenting to a hospital without PCI capability and who cannot be transferred to undergo PCI within 90 minutes should be treated with fibrinolytic therapy within 30 minutes as a systems goal”

4. Background – Challenges to First medical contact to PCI in 90 minutes Patients in rural areas far from PCI Centers –Only 1200/5000 hospitals are PCI capable 4% of STEMI patients who are transferred achieve DTB <90 minutes 1 –↑ 13% with statewide regionalization efforts 2 Method of choice for primary reperfusion in these patients may be fibrinolysis 1 Nallamothu BK et al. Circulation. 2005 2 Jollis JG et al. JAMA. 2007

5. Objectives Assess the performance of fibrinolytic therapy within the 30 minute guideline in contemporary practice Evaluate patient characteristics associated with the timeliness of fibrinolysis Determine association of DTN times with patient outcomes

6. Methods – Study population ACTION –GWTG Registry January 2007-June 2008 30,193 patients with STEMI at 286 hospitals Fibrinoytic therapy - 3,219 STEMI patients in 178 hospitals

7. Methods – Variables Co-variates –Patient demographics (age, race, gender) –Medical history –Clinical characteristics on presentation Outcomes –Time to fibrinolysis –In-hospital events Mortality Composite outcome – Mortality, stroke, cardiogenic shock

8. Methods – Statistical analysis Association of patient factors and time to fibrinolysis –Linear generalized estimating equations (GEE) Association of time to fibrinolysis and outcomes –GEE model

9. DemographicsPresentation characteristics Age (year), median, IQR59.0 (51.0-68.0)Clinical symptoms Gender, male2358 (73.3) Signs of CHF299 (9.3) Race, white2804 (87.1) Heart rate >100 bpm392 (12.2) Insurance status, private1835 (57.0) Systolic BP <90 mmHg173 (5.4) Body mass index (kg/m 2 )28.3 (25.3-32.2)Transported by EMS988 (30.7) Medical historyHospital characteristics Hypertension1823 (56.6)Non-PCI (versus PCI)2872 (89.2) Diabetes mellitus614 (19.1)Region Current/recent smoker1512 (47.0) West432 (13.4) Dyslipidemia1545 (48.0) Northeast298 (9.3) Prior MI589 (18.3) Midwest1041 (32.2) South1448 (45.0) Patient Characteristics (n=3,219)

10. Results – Distribution of DTN times Median DTN 34.0 minutes (IQR 22.0 - 54.0) 1,432/3,219, 44.5% met the ACC/AHA guideline ≤ 30 minutes

11. Variable Adjusted Estimate* 95% CI (Lower) 95% CI (Upper) p-value: (Individual) p-value: (Global) Patient demographics Women (vs. men) Age (year) 17.8 11.9 24.1<.0001 55 to 64 (vs. <55) -0.3 -5.6 5.30.90860.0434 65 to 74 (vs. <55) -1.1 -8.6 7.10.7875 ≥75 (vs. <55) 12.0 1.8 23.20.0200 White (vs. other race) -6.7-14.2 1.40.1039 Presentation features Transported by EMS-19.3-24.5-13.7<.0001 Systolic blood pressure <90 mmHg-10.8-19.4 -1.30.0263 Time or presentation Weekday, evening (vs. Weekday, day) 4.0 -3.1 11.70.27560.0156 Weekday, night (vs. Weekday, day) 12.0 3.8 20.90.0036 Weekend, day (vs. Weekday, day) 1.1 -8.0 11.30.8181 Weekend, evening (vs. Weekday, day) 2.8 -6.3 12.70.5605 Weekend, night (vs. Weekday, day) 13.4 3.0 24.80.0104

12. OutcomeOutcome (%) Adjusted OR (95% CI) p-value Death3.1% vs 4.4%0.79 (0.50-1.25)0.3126 Death /shock /stroke6.2% vs 8.8%0.74 (0.56-0.98)0.0356 Association of DTN time and Outcomes: ≤30 minutes versus >30 minutes

13. Potential Limitations Selection bias (voluntary registry) –Underestimates treatment delays Observational study –Unmeasured confounders Physician experience and treatment preferences Systems factors Sicker patients = longer treatment delays –Yet patients in shock treated as quickly

14. Conclusions Timely fibrinolytic therapy associated with better outcomes DTN time < 30 min seen < one-half patients –Delays in women, elderly, and after-hours presentations Efforts to optimize STEMI care, including regional systems, should focus on shortening reperfusion times for patients who receive primary fibrinolysis as well as those who receive primary PCI

15. Back up slides

16. Potential reasons for treatment delays Delay in diagnosis –Atypical signs and symptoms –Door to ECG times, minutes Women, median 9 (IQR 4 to 14) Men, median 5 (IQR 2 to 12) System factors at small, rural hospitals –Training of emergency providers (board certification) –Variation in protocols – e.g. CXR, cardiology consultation Patient factors –Variation in provider and patient risk preferences

17. VariableLevelMedian25 th %75 th %p-value Presentation characteristics Systolic BP (mmHg)≥90 mmHg34.022.054.00.1622 <90 mmHg31.023.046.0 Transported byNo36.024.057.0<.0001 Yes28.019.045.0 Time of PresentationWeekday, day32.021.052.00.0077 Weekday, evening33.022.052.0 Weekday, night36.025.058.0 Weekend, day33.022.545.5 Weekend, evening33.021.557.0 Weekend, night35.025.057.0 Hospital characteristics RegionWest36.023.560.00.0005 Northeast35.023.054.0 Midwest35.024.055.0 South32.021.051.0 Type of hospitalPCI27.017.052.0<.0001 Non-PCI35.023.054.0

18. VariableMedian 25th Percentile 75th Percentile p-value (Global) Patient characteristics Age (year)<5531.021.050.0<.0001 55-6433.022.051.0 65-7435.024.055.0 ≥7541.025.067.0 GenderMale32.021.050.0<.0001 Female38.025.061.5 RaceCaucasian34.022.053.00.8096 Black34.021.066.0 Asian32.014.057.0 Hispanic34.521.052.0 Other35.021.060.0