1. CVD Critical Pathways Group 2005 Teleconferences This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. August 10, 2005

2. Faculty Gregg C. Fonarow, MD Eliot Corday Professor of Medicine and Cardiovascular Science Director, Ahmanson-UCLA Cardiomyopathy Center UCLA Division of Cardiology UCLA Medical Center Los Angeles, California

3. The Network for Continuing Medical Education requires that CME faculty disclose, during the planning of an activity, the existence of any personal financial or other relationships they or their spouses/partners have with the commercial supporter of the activity or with the manufacturer of any commercial product or service discussed in the activity. Disclosure Statement

4. Gregg C. Fonarow, MD, has served as a consultant to and has received research support from GlaxoSmithKline, Pfizer Inc., and Scios Inc. He has also received honoraria from Merck & Co., Inc. The team from Aurora Sinai Medical Center reports no such relationships. Faculty Disclosure Statement

6. Cost-effectiveness of CVD Therapies: Which Therapies Provide Good Value? Gregg C. Fonarow, MD

11. HPS Simvastatin: Cause-Specific Mortality Risk ratio and 95% CI STATIN Better PLACEBO Better 17% SE 4 reduction (2P<0.0001) 5% SE 6 reduction (NS) 13% SE 4 reduction (2P<0.001) Heart Protection Study Collaborative Group. Lancet. 2002;360:7 - 22. Reprinted with permission from Elsevier Science. 570 (5.6%) 547 (5.3%) NONVASCULAR 21 16 Nonmedical 90 82 Other medical 345 359 Neoplastic 114 90 Respiratory 1507 (14.7%) 1328 (12.9%) ALL CAUSES 230 194 Other vascular 707 587 Coronary 937 (9.1%) 781 (7.6%) ANY VASCULAR Placebo (10,267) Nonvascular Vascular Simvastatin (10,269) Cause of Death 0.6 0.8 1.0 1.2 1.4 0.4

14. Discounted Incremental Costs, Effects, and Cost-effectiveness During 5-Year Mean Follow-up by Risk Group and Overall Adapted with permission from Mihaylova B, et al. Lancet. 2005;365:1779-1785. US dollar figures computed at a conversion rate of $1.80 per British pound. MVE Vascular deaths Cost per Risk Group Incremental avoided per Cost per avoided per vascular death (5-year MVE risk) cost 1000 persons MVE avoided 1000 persons avoided 1 (12%) £ 1164/$2095 37 £ 31,100/$55,980 4 £ 296,300/$533,340 2 (18%) £ 1062/$1912 58 £ 18,300/$32,940 7 £ 147,800/$266,040 3 (22%) £ 987/$1777 80 £ 12,300/$22,140 13 £ 78,900/$142,020 4 (28%) £ 893/$1607 93 £ 9600/$17,280 18 £ 46,600/$89,280 5 (42%) £ 630/$1134 141 £ 4500/$8100 29 £ 21,400/$38,520 Overall £ 947/$1705 82 £ 11,600/$20,880 14 £ 66,600/$119,880 *Discounted at 3.5% per annum. MVE = major vascular event.

15. CURE Primary End Point: MI/Stroke/CV Death Months of Follow-up *In addition to other standard therapies. Adapted with permission from Yusuf S, et al. N Engl J Med. 2001;345:494-502. Clopidogrel + Aspirin* (n=6259) Placebo + Aspirin* (n=6303) P <.001 N=12,562 20% Relative Risk Reduction 0.12 0.14 0.10 0.06 0.08 0.00 0.04 0.02 Cumulative Hazard Rate 3 6 9 0 12

16. Long-term Cost-effectiveness of Clopidogrel in Patients With NSTEMI Adapted with permission from Weintraub WS, et al. J Am Coll Cardiol. 2005;45:838-845. *Based on Medicare costs and Framingham and Saskatchewan life expectancy estimates; N=12,562. ICER = incremental cost-effectiveness ratio; LYG = life-year gained. Cost-effectiveness of Clopidogrel* 93.9% $6318 0.0699 $442 Framingham Medicare 97.7% $6475 0.0682 $442 Saskatchewan Medicare No direct costs beyond trial period % <50,000/LYG ICER ∆ Life-Years ∆ Cost

17. CREDO Study: 1-Year Primary Outcome 27% Relative Risk Reduction Months 3 0 6 9 12 0 5 15 10 Death, MI, or Stroke (%) P =.02 8.5% 11.5% Clopidogrel n=1053 Placebo n=1063 Adapted with permission from Steinhubl SR, et al. JAMA. 2002;288:2411-2420. NNT=33

18. CREDO Study: Benefit of Clopidogrel in PCI Patients at Various Time Intervals - 12 - - 8 - - 4 - - 0 - 4.6 Rand. to 1 Year Rand. to Day 28 Day 29 to 1 Year Combined Endpoint Occurrence (%) MI, Stroke, or Death – ITT Population Clopidogrel* Placebo* 37.4% RRR P =.04 19.7% RRR P =.21 26.9% RRR P =.02 *Plus aspirin and other standard therapies. † Steinhubl S, et al. JAMA. 2002;288:2411-2420. ‡ Steinhubl S. 75th Scientific Sessions of the AHA; November 18, 2002; Chicago, Ill. 8.5 † 11.5 † 5.5 ‡ 6.9 ‡ 2.9 ‡ 4.6 ‡

19. Cost-effectiveness of Prolonged Clopidogrel Therapy After PCI Adapted with permission from Cowper PA, et al. J Am Coll Cardiol. 2005;45:369-376. Modeled Outcomes and Cost-effectiveness N=3976. Total Sample Variable Clopidogrel No Clopidogrel Total Cost* $3,715 $2,819 Outcomes MI (1 month to 1 yr) 3.24% 5.80% Cost-effectiveness $/MI avoided $34,336 $/yr of life saved $15,696 *Between 1 and 12 months following PCI.

20. Cost-effectiveness of Prolonged Clopidogrel Therapy After PCI Adapted with permission from Cowper PA, et al. J Am Coll Cardiol. 2005;45:369-376. N=3976. Modeled Outcomes and Cost-effectiveness High-Risk Subset Low-Risk Subset No No Variable Clopidogrel Clopidogrel Clopidogrel Clopidogrel Total Cost* $4,082 $3,307 $3,311 $2,328 Outcomes MI (1 month to 1 yr) 4.46% 8.0% 2.06% 3.70% Cost-effectiveness $/MI avoided $21,893 $59,939 $/yr of life saved $10,333 $26,568 *Between 1 and 12 months following PCI

22. ISAR-REACT Primary End Point: 30-Day Death/MI/UTVR P = NS Death/MI/UTVR P = NS UTVR P = NS Death Abciximab + Clopidogrel Placebo + Clopidogrel Abciximab + Clopidogrel Placebo + Clopidogrel Abciximab + Clopidogrel Placebo + Clopidogrel UTVR = urgent target-vessel revascularization. Adapted with permission from Kastrati A, et al. N Engl J Med . 2004;350:232-238. % of Patients

23. High Cost of Post-MI Heart Failure Impact of Heart Failure on Cost of Managing Post-MI Patients $31,426 $44,997 0 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000 Post-MI Patients Post-MI Patients With Heart Failure Mean Annual Cost of Management 50,000 $13,571 per year for patients who develop heart failure Akhras KS, et al. Abstract presented at: Heart Failure Society of America 2003 Scientific Meeting; September 21-24, 2003; Las Vegas, Nev. Dollars (n=5298) (n=2345)

24. Impact of Eplerenone on Relative Risk of Total Mortality Post-MI With LVD Months Since Randomization Cumulative Incidence (%) 22 0 2 20 16 18 14 12 10 8 6 4 RR=.85 (95% CI, .75-.96) P =.008 Placebo (n=3,313) Eplerenone (n=3,319) 36 33 30 27 24 21 18 15 12 9 6 3 0 Pitt B, et al. N Engl J Med . 2003;348:1309-1321. CI = confidence interval; RR = relative risk.

25. Early Benefits of Eplerenone When Added to Standard Post-MI Patient Care Pitt B, et al. N Engl J Med . 2003;348:1309-1321. All Cause Mortality Cardiovascular Mortality Sudden Cardiac Death Heart Failure Hospitalization 30 Days -31 -32 -37 -18 -50 -45 -40 -35 -30 -25 -20 -15 -10 -5 0 5 10 Relative Risk (%)

26. Cost-effectiveness of Eplerenone vs Placebo in MI Patients With LV Dysfunction and HF Adapted with permission from Weintraub WS, et al. Circulation. 2005;111:1106-1113. Cost-effectiveness of Eplerenone N=6632. ∆ Cost, $ ∆ Effectiveness ICER, $ <50,000/LYG, % No added costs resulting from life-years saved Life-years Framingham 1391 0.1014 13,718 96.7 Saskatchewan 1391 0.0636 21,876 93.8 Worcester 1391 0.1337 10,402 98.8 LYG indicates life-years gained.

27. Critical Pathways for UA/NSTEMI Unstable Angina/ Non–ST-elevation MI* ASA, Clopidogrel,  -blockers, ACEI, statin Heparin or LMWH Conservative Strategy Invasive Strategy DC Home or ETT Hour 8-12 Cath/PCI Hour (0-6) D/C Home Hour 8-16 D/C Day Hour 18-24 + Rest pain Adapted from UCLA Clinical Pathway for ACS. Available at: www.med.ucla.edu/champ. ECG + and/or Troponin + Troponin - 6-hr Troponin - / ECG - ASA, clopidogrel,  -blockers, ACEI, statin, omega 3, and exercise

29. CHAMP Study: Clinical Events for the First Year After Discharge for Acute MI Fonarow GC, et al. Am J Cardiol. 2001;87:819-822. Event Rate, % Recurrent MI Heart Failure Hospitalization Total Mortality Pre-CHAMP Post-CHAMP 7.8 4.7 14.8 7.0 3.3* 2.6 7.6* 3.3* * P <0.05

30. 256 AMI pts discharged in 92/93 pre-CHAMP compared to 302 pts in 94/95 post-CHAMP UCLA Med Center Accounting Model, total costs averaged over each pt dc; meds at AWP Fonarow GC, et al. Am J Cardiol. 2001;87:819-822. CHAMP: Economic Analysis P <0.001

31. Variation in Acute MI Care Quality in 1085 Hospitals and Its Association With Mortality Rates 86,735 AMI patients in NRMI IV treated between 7/00 and 3/01. ACC/AHA Class I therapy. Hospitals divided into quartiles to composites of quality. Peterson ED. Circulation. 2002;106:II-722. Abstract. Median Performance Lagging Hospitals Leading Hospitals on Care Processes (n=271) (n=271) Aspirin <24 h 73% 93% β - blocker <24 h 50% 86% Reperfusion 50% 71% DC ACEI 40% 70% DC Lipid Therapy 58% 80% Smoking Advice 7% 65% Mortality 17.6% 11.9%

32. Performance Matters! Reprinted with permission from Peterson ED. Presented at: Annual Scientific Sessions of the AHA; November 17-20, 2002; Chicago, Ill. Relationship Between Process and Outcome in CRUSADE 5.9 5.0 4.6 3.6 0 1 2 3 4 5 6 7 Hospital Composite Adherence Quartiles In-hospital Mortality (%) <65% 65%-75% 75%-80% >80%

33. Featured Institution Aurora Sinai Medical Center Milwaukee, Wisconsin

35. Progress Checklist: Immediate Goals Circulate discharge plan and other tools to all cardiology, ED, and CV nursing staff for comments  Circulate pathways to all cardiology, ED, and CV nursing staff for comments  Develop draft pathways  Assemble team and set up meeting of working group 

36. Progress Checklist: Short-term Goals/Activities Grand rounds/conference: Cardiology/IM  Grand rounds/conference: Emergency Dept.  Grand rounds/conference: Nursing  Circulate memo  Launch critical pathways  Finalize critical pathways 

37. Progress Checklist: Long-term Goals/Activities  NRMI  AHA Get With The Guidelines  ACC National Cardiovascular Data Registry  CRUSADE  GRACE  REACH  Other Monitor data: which registry? 

38. Question-and-Answer Session

39. Concluding Remarks Gregg C. Fonarow, MD Next program: Wednesday, September 14, 2005 at 12:00 Noon Eastern Time (9:00 AM Pacific) Topic: The CRUSADE National Quality Improvement Initiative: 2005 Update Faculty: Christopher P. Cannon, MD