1. 0009COR1 A CRUSADE to Improve Quality of Care for ACS Patients Eric D. Peterson, MD, MPH Associate Professor of Medicine Director of CV Outcomes and Quality Duke Clinical Research Institute (DCRI) Duke University Medical Center Eric D. Peterson, MD, MPH Associate Professor of Medicine Director of CV Outcomes and Quality Duke Clinical Research Institute (DCRI) Duke University Medical Center

2. Annual Admissions for Acute Coronary Syndrome (ACS) 1.4 Million Non-ST-segment elevation ACS AND GROWING! 600,000 ST-segment elevation MI ~ 2.0 MM patients admitted to CCU or telemetry annually

3. DiscoveryDiscovery Outcomes Clinical Trials GuidelinesGuidelines Performance Indicators Performance Indicators AssessmentAssessment The Cycle of Clinical Therapeutics Califf R, Peterson, E JACC 2002;40:1895-901 Califf R, Peterson, E JACC 2002;40:1895-901

4. ST-segment Elevation Time Dependent: Emergency Evaluation of ACS Chest pain or Short of Breath Unstable Angina ST-segment Depression – + + Presentation ECG Diagnosis Braunwald E,2002 http://www.acc.org/clinical/guidelines/unstable/unstable Normal Markers Acute MI – + Rule-Out

5. Troponin as a Marker of Increased Risk in ACS

6. 10 ng/mL troponin standard material, measured by 13 participating cTnI assays, in duplicate samples: Systematic Variation Between cTnI Assays Conclusion: Within assay reproducibility good, but across assay results varied >30-fold different! Clin Chem 2001;47:431-437

7. US PURSUIT Results: Treatment Effect of Eptifibatide in High Risk Subgroups Death or MI Men Old age tertile No diabetes mellitus Low age tertile Middle age tertile Women Diabetes mellitus

8. USING THE TIMI RISK SCORE TO PREDICT BENEFIT OF GP IIb-IIIa THERAPY Morow DA,Eur HeartJ 2002;23:223-229 Number of risk factors NNT72NA17226.2

9. Benefits of GP IIb-IIIa by Troponin Status in Clinical Trials TnT-negative TnT-positive PARAGON B PRISM CAPTURE COMBINED 0.125 1 1 22 Newby, Circulation 2001 0.125 0.50.5

10. In-hospital Mortality By Early GP IIb-IIIa Inhibitor Use (within 24 hrs) † Cumulative Q1 2003 Data ∆ 42%  P < 0.0001 ∆ 42%  P < 0.0001 *Includes patients who received late GP IIb-IIIa inhibitor (> 24 hrs) therapy. † Unadjusted for risk.

11. Mortality Benefits of Early GP IIb-IIIa Inhibitor: Results from Clinical Trials, NRMI and CRUSADE NRMI NSTEMI # (N=60,770) 95% CIOdds Ratio 1.01.02.02.00.50.5 No Early GP IIb-IIIa Inhibitor Better Early GP IIb-IIIa Inhibitor Better 0.91 (0.81, 1.03) CRUSADE ACS † (n=31,257) 0.88 (0.79, 0.97) 0.90 (0.78, 1.04) 6 RCTs ACS * (n=31,402) Boersma Lancet 2002;359:189-98 # Peterson JACC 2003;42:45-53 † Adjusted for risk, treatment, hospital factors Boersma Lancet 2002;359:189-98 # Peterson JACC 2003;42:45-53 † Adjusted for risk, treatment, hospital factors

12. Adjusted Mortality by Early GP IIb-IIIa Inhibitor Results by Troponin Status 95% CIOdds Ratio 1.01.02.02.00.50.5 No Early GP IIb-IIIa Inhibitor Better Early GP IIb-IIIa Inhibitor Better CRUSADE Overall (n=31,257) 0.90 (0.78, 1.04) 0.84 (0.71, 0.99) CRUSADE Trop Pos (n=25,848) (n=25,848) CRUSADE Trop Pos (n=25,848) (n=25,848) CRUSADE Trop Neg (n=5,964) (n=5,964) CRUSADE Trop Neg (n=5,964) (n=5,964) 0.95 (0.46, 1.35) Excludes pts transferred out, GP IIb-IIIa contraindications

13. In-hospital Events by “Upfront” vs. “In-lab Only” GP IIb-IIIa Inhibitor Use (Patients receiving PCI < 48 hrs + GP IIb-IIIa; n= 5,833) Adjusted OR 0.95; (95% CI 0.60-1.15) Adjusted OR 0.83; (95% CI 0.63-1.09) Peterson ACC 2003

14. 6 mo Death/ MI/ Rehosp (%) CONS INV TACTICS-TIMI 18 Early Intervention vs Conservative By Troponin Status TreatmentInteractionP<0.001 N=414 N=396N=463N=495

15. 6 mo Death/ MI/ Rehosp (%) CONSINV TACTICS-TIMI 18 Early Intervention vs Conservative By TIMI Risk Score

16. CRUSADE: Benefits of Early Catheterization within 48 hrs by Risk Group - Bhatt AHA 2002

17. Does Current Practice Mirror Guidelines Recommendations?

18. AK (0) WA (11) OR (5) CA (43) ID (1) NV (1) MT (0) WY (0) CO (4) NM (2) ND (1) SD (2) NE (3) KS (7) OK (5) TX (19) MN (6) IA (4) MO (12) AR (5) LA (5) WI (5) MI (23) MI UT (1) AZ (14) HI (3) IL (14) IN (9) KY (13) TN (14) MS (8) AL (9) GA (12) FL (49) SC (7) NC (13) VA (17) OH (34) WV (4) PA (48) NY (40) MD (13) ME (1) VT (1) NH (2) NJ (14) MA (14) CT (9) DE (3) RI (0) DC (4) Active sites = 430 56,400 Patients CRUSADE Site Distribution

19. Hospital Presentation Characteristics in CRUSADE l Qualifying Criteria ST-segment depression 39% Transient ST-segment elevation 11% Positive cardiac markers 88% l Baseline cardiac markersDrawnPositive CK-MB85%35% TnT/TnI97%84% l Bedside assays CK-MB9% Troponin11% l Qualifying Criteria ST-segment depression 39% Transient ST-segment elevation 11% Positive cardiac markers 88% l Baseline cardiac markersDrawnPositive CK-MB85%35% TnT/TnI97%84% l Bedside assays CK-MB9% Troponin11%

20. Baseline Characteristics: CRUSADE vs. ACS Clinical Trials PURSUITPRISM-PLUSGUSTO-IV ACSCRUSADE VariablePURSUITPRISM-PLUSGUSTO-IV ACSCRUSADE (n = 9461)(n = 1915)(n = 7800)(n = 41,267) Mean age ± SD (yrs)63 ± 1163 ± 1265 ± 1168 ± 13 Female sex (%)36323840 Diabetes mellitus (%)23232233 Prior MI (%)32433131 Prior CHF (%)1110817 Prior PCI (%)13101021 Prior CABG (%)1215820 ST depression (%)50588039 PURSUITPRISM-PLUSGUSTO-IV ACSCRUSADE VariablePURSUITPRISM-PLUSGUSTO-IV ACSCRUSADE (n = 9461)(n = 1915)(n = 7800)(n = 41,267) Mean age ± SD (yrs)63 ± 1163 ± 1265 ± 1168 ± 13 Female sex (%)36323840 Diabetes mellitus (%)23232233 Prior MI (%)32433131 Prior CHF (%)1110817 Prior PCI (%)13101021 Prior CABG (%)1215820 ST depression (%)50588039 NEJM, 1998 Lancet, 2001 NEJM, 1998 Lancet, 2001

21. CRUSADE vs. ACS Clinical Trials: Early Mortality Rates PURSUIT (n = 9,461) PRISM-PLUS (n = 1,915) GUSTO IV- ACS (n = 7,800) CRUSADE (n = 41,267) 1.8% 1.9% 1.8% 4.7% 7-day mortality rate In-hospital mortality rate NEJM, 1998 Lancet, 2001 NEJM, 1998 Lancet, 2001

22. Goal for CRUSADE: Improve Adherence to ACC/AHA Guidelines Aspirin Clopidogrel Beta Blocker Heparin (UFH or LMWH) GP IIb-IIIa Inhibitor All receiving PCI Aspirin Clopidogrel Beta Blocker Heparin (UFH or LMWH) GP IIb-IIIa Inhibitor All receiving PCI Aspirin Clopidogrel Beta Blocker ACE Inhibitor Statin/Lipid Lowering Smoking Cessation Cardiac Rehabilitation Acute Therapies Discharge Therapies Circulation, JACC 2002 - ACC/AHA Guidelines update

23. Acute Medication Use (within 1st 24 hours) 94%94% 79%79% 84%84% 36%36% 0% 20% 40% 60% 80% 100% ASAASA BetaBlockersBetaBlockersHeparin (LMW + UFH) Heparin GP IIb-IIIa Inhibitors Inhibitors

24. Gap between Leading and Lagging Hospital Quartiles: Acute Care Leading Centers Lagging Centers

25. Invasive Cardiac Procedures 62%62% 43%43% 37%37% 23%23% 0% 15% 30% 45% 60% 75% CathCath Cath < 48 hr PCIPCICABGCABG 12%12% PCI < 48 hr Median Times Cath - 28 hrs Cath - 28 hrs PCI - 26 hrs PCI - 26 hrs CABG - 71 hrs CABG - 71 hrs

26. Acute Therapies (< 24 hrs) by Peak Troponin Level 0 10 20 30 40 50 60 70 80 90 100 Tn 0-1 xULN Tn 1-2 xULN Aspirin B-Blockers Heparin GP IIb/IIIa Clopidogrel Aspirin B-Blockers Heparin GP IIb/IIIa Clopidogrel (UFH + LMWH) Aspirin B-Blockers Heparin GP IIb/IIIa Clopidogrel Aspirin B-Blockers Heparin GP IIb/IIIa Clopidogrel (UFH + LMWH) Tn 2-5 xULN Tn > 5 xULN P < 0.001 Roe, ACC 2003

27. Use of Invasive Procedures by Peak Troponin Level Cath PCI 0 10 20 30 40 50 60 70 80 0-1 xULN1-2 xULN2-5 xULN> 5 xULN Peak Troponin Ratio % CABG Roe, ACC 2003

28. Peak Tn Ratio 1-2 X ULN 2-5 X ULN > 5 X ULN Peak Tn Ratio 1-2 X ULN 2-5 X ULN > 5 X ULN Normal 1 1 1.5 2.0 2.5 Adjusted Risk of In-Hospital Mortality by Peak Troponin Level P = 0.03 P = 0.02 P < 0.001 P = 0.03 P = 0.02 P < 0.001 Roe, ACC 2003

29. Discharge Medication Use LVEF < 40%, CHF, DM, HTN # Known hyperlipidemia,  TC,  LDL 90% 83% 0% 20% 40% 60% 80% 100% ASA Beta Blockers ACE-Inhibitors* 61% Lipid-Lowering Agent # 79% 56% Clopidogrel

30. Discharge Interventions 59%59% 72%72% 42%42% 66%66% 0% 20% 40% 60% 80% 100% Lipid Panel Drawn Drawn DietaryCounselingDietaryCounseling Cardiac Rehab Referral Referral SmokingCessationCounselingSmokingCessationCounseling

31. Gap between Leading and Lagging Hospital Quartiles: Discharge Care * LVEF < 40% # Known hyperlipidemia * LVEF < 40% # Known hyperlipidemia # # Leading Centers Lagging Centers

32. 0009COR32 Paradoxical Care: Failing to Treat High Risk ACS

33. Risk of ACS in Elderly* * Kulkarni S et al ACC 2003 CRUSADE Presentation

34. Medical Therapy in the Elderly <75 yrs≥75 yrsAdj. OR (95%CI)** Acute Aspirin9288*0.91 (0.83, 1.00) Beta-Blocker7975*0.91 (0.84, 0.99) Clopidogrel4132*0.82 (0.76, 0.88) Gp 2b3a4122*0.64 (0.59, 0.69) Cath (<48 hrs)4616*0.51 (0.42-0.59) PCI (≤ 48hrs)3214*0.60 (0.55, 0.66) * Unadjusted p<0.05 ** Comparison of age ≥75 with <75 yrs. Adjusted for gender, race, comorbidity, cardiac markers, insurance status, hospital features, and clustering effects (#elderly treated, similar outcomes). <75 yrs≥75 yrsAdj. OR (95%CI)** Acute Aspirin9288*0.91 (0.83, 1.00) Beta-Blocker7975*0.91 (0.84, 0.99) Clopidogrel4132*0.82 (0.76, 0.88) Gp 2b3a4122*0.64 (0.59, 0.69) Cath (<48 hrs)4616*0.51 (0.42-0.59) PCI (≤ 48hrs)3214*0.60 (0.55, 0.66) * Unadjusted p<0.05 ** Comparison of age ≥75 with <75 yrs. Adjusted for gender, race, comorbidity, cardiac markers, insurance status, hospital features, and clustering effects (#elderly treated, similar outcomes).

35. Acute Risks and Treatment of ACS in Women 2003 4 th Quarter CRUSADE Risks Treatment

36. Acute Risks and Treatment of ACS in Diabetes* * CRUSADE 4th Quarter Treatment Risks

37. Acute Treatment of CHF 2003 4 th Quarter CRUSADE Treatment Risks

38. If the guidelines are implemented, Do outcomes improved?

39. Performance Matters! Relationship between Process and Outcome 5.9 5.0 4.6 3.6 Peterson ED 2002 AHA

40. 0009COR40 Can We Improve Care?

41. Quality Improvement Interventions: Site Predictors of Success Strong clinician “champions” Strong clinician “champions” Administrative support for CQI Administrative support for CQI Shared targets for improvement Shared targets for improvement High-quality data feedback High-quality data feedback Strong clinician “champions” Strong clinician “champions” Administrative support for CQI Administrative support for CQI Shared targets for improvement Shared targets for improvement High-quality data feedback High-quality data feedback Bradley E, JAMA 2001 - Use of Beta-Blockers Post-MI

42. Practical Steps to Improve the Use of Evidence- Based Therapies for Non-ST  ACS Identify local Cardiology and ED physician champions Identify local Cardiology and ED physician champions Secure institutional commitment to improved pt care Secure institutional commitment to improved pt care Develop educational materials to improve all physicians’ knowledge of the ACC/AHA guidelines Develop educational materials to improve all physicians’ knowledge of the ACC/AHA guidelines Track adherence to ACC/AHA recommendations Track adherence to ACC/AHA recommendations Identify areas for QI Identify areas for QI Provide standard QI tools Provide standard QI tools Give ongoing quarterly feedback Give ongoing quarterly feedback Identify local Cardiology and ED physician champions Identify local Cardiology and ED physician champions Secure institutional commitment to improved pt care Secure institutional commitment to improved pt care Develop educational materials to improve all physicians’ knowledge of the ACC/AHA guidelines Develop educational materials to improve all physicians’ knowledge of the ACC/AHA guidelines Track adherence to ACC/AHA recommendations Track adherence to ACC/AHA recommendations Identify areas for QI Identify areas for QI Provide standard QI tools Provide standard QI tools Give ongoing quarterly feedback Give ongoing quarterly feedback

43. Trends in Acute Therapy Adherence

44. Trends in Discharge Therapy Adherence

45. Trends in Discharge Recommendations Adherence

46. Conclusions: Quality ACS Care Clinicians need to rapidly assess pt risk Risk factors + markers Pts at highest risk tend to benefit from most aggressive interventions However, current ACS care demonstrates: Wide variability between leading and lagging centers Paradoxical care Given tight links between care and outcome We need to work together develop successful ACS quality improvement efforts Clinicians need to rapidly assess pt risk Risk factors + markers Pts at highest risk tend to benefit from most aggressive interventions However, current ACS care demonstrates: Wide variability between leading and lagging centers Paradoxical care Given tight links between care and outcome We need to work together develop successful ACS quality improvement efforts

47. How to Take This Home… Look critically at your data Identify targets Look at your system Learn from your neighbors Make practical, actionable plans Follow-up Never be satisfied Look critically at your data Identify targets Look at your system Learn from your neighbors Make practical, actionable plans Follow-up Never be satisfied