1. COURAGE Economic Results of the COURAGE Trial William S. Weintraub, MD Chief of Cardiology Christiana Care Health System Professor of Medicine, Thomas Jefferson University

2. Health Care Economics Purpose: To compare resource utilization across treatment arms To compare costs across treatment arms If one therapy offers better outcome at higher cost, perform an incremental cost- effectiveness analysis in cost per quality adjusted life year gained

3. Health Care Economics Methods: DRG applied to hospitalization, CPT codes to outpatient care, 2004 codes Costs from Medicare reimbursement Medication costs from Red Book AWP Average Medicare costs beyond trial period Quality adjustment measuring utility with standard gamble Survival estimates based on Framingham Distribution of cost and outcome by bootstrap analysis

4. In-Trial and Cumulative Costs PCI Group (n=1149) OMT Group (n=1138)  (PCI Group- OMT Group) 95% CI Initial cost$12,162$752$11,41011,139, 11,712 In-trial cumulative cost for 1 year$20,170$8,643$11,52710,359, 12,608 In-trial cumulative cost for 2 years$23,554$11,806$11,74810,803, 12,914 In-trial cumulative cost for 3 years$26,847$15,653$11,1949,883, 12,307 Total in-trial costs ($)*$34,843$24,718$10,1258,082, 12,167 Revascularization Hospitalization $14,901$4,368$10,5329,888, 11,177 Other cardiovascular Hospitalization $9,499$9,844-$345-1,971, 1,280 Medication$3,418$3,573-$155-492, -37 Outpatient services$7,025$6,933$92-336, 514 Cost beyond trial period$64,978$65,651-$673-2,781, 1,433 Lifetime Cost$99,820$90,370$9,4516,729, 12,173

5. Life Expectancy (Framingham) ItemPCI Group (n=1149) OMT Group (n=1138)  (PCI Group- OMT Group) 95% CI In-trial life years (mean±SD) 4.15±1.504.12±1.510.03-0.09, 0.15 In-trial quality adjusted life years (mean±SD) 3.56±1.343.51±1.360.05-0.06, 0.17 Life years lost due to events (mean±SD) 0.90±2.450.95±2.470.06-0.26, 0.15 Quality adjusted life years due to events (mean±SD) 0.79±2.160.82±2.220.04-0.19, 0.17 Life expectancy* (mean±SD) 12.26±4.7812.22±4.820.04-0.29, 0.50 Quality Adjusted Life expectancy* (mean ± SD) 9.95±3.859.89±3.890.06-0.21, 0.43

6. Utility VisitPCI GroupOMT GroupP-Value Baseline0.90 ± 0.20 (n=775)0.87 ± 0.22 (n=748)0.66 1-month0.92 ± 0.19 (n=665)0.91 ± 0.20 (n=699)0.14 3-month0.93 ± 0.17 (n=669)0.92 ± 0.19 (n=678)0.008 6-month0.93 ± 0.17 (n=701)0.93 ± 0.15 (n=665)0.20 1-year0.93 ± 0.17 (n=648)0.93 ± 0.16 (n=636)0.53 2-year0.93 ± 0.17 (n=550)0.92 ± 0.17 (n=532)0.59 3-year0.92 ± 0.20 (n=385)0.90 ± 0.21 (n=379)0.004

7. Cost-Effectiveness Analysis 35.410.1168,0190.056$9,451$90,370$99,820 Lifetime, QALY (3% discount) 25.73.3262,1160.036$9,451$90,370$99,820 Lifetime, LY (3% discount) 17.00206,2290.0491$10,125$24,718$34,843 In-trial, QALY (3% discount) 14.00299,5180.0338$10,125$24,718$34,843 In-trial, LY (3% discount) %< $100,000 /LYG %< $50,000 /LYG ICER  (PCI - OMT) Cost OMT Group (n=1138) Cost PCI Group (n=1149) LYs or QALYs gained with PCI

8. Joint Distribution of Cost & Effectiveness Differences Lifetime Timeframe, Cost/QALY Gained

9. Cost-Effectiveness Acceptability Curve Lifetime Timeframe, Cost/QALY Gained

10. -0.50.0 0.5 0.4 0.6 0.8 1.0 1.2 1.4 1.6 Mean Cost Difference (PCI-Medial Therapy in $10000s) Mean Effective Difference in QALYs (PCI-Medical Therapy) Joint Distribution of Cost & Effectiveness Differences Bayesian Probabilistic Sensitivity Analysis Lifetime Timeframe, Cost/QALY Gained 50% 95% 99%

11. Cost-Effectiveness Acceptability Curve Bayesian Probabilistic Sensitivity Analysis Lifetime Timeframe, Cost/QALY Gained 0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 Incremental CE Ratio Threshold ($) Probability of ICER Below Threshold 100,000150,000200,000 50,000

12. $123,5938.2%20%28%147 (741)222 (792)All 3 domain improvement $105,2729.6%35%45%259 (741)353 (792)Any 2 domain improvement $300,7423.4%75%79%557 (741)622 (792)Any 1 domain improvement $124,2338.1%56%64%409 (729)505 (786)Quality of Life $154,5806.6%44%50%323 (738)396 (787)Angina Frequency $112,8769.0%42%51%300 (707)386 (751)Physical Limitation ICER  (PCI - OMT) Improvement In OMT Group Improvement In PCI Group OMT Group PCI Group Cost-Effectiveness Analysis for Improvement of Angina-Related Health Status At 6 Months

13. Conclusions PCI as an initial management strategy in the setting of stable CAD has not been shown to reduce the incidence of Death or MI PCI has not been shown to prolong life expectancy PCI+OMT does offer better control of angina than OMT alone PCI+OMT was not shown to be a cost-effective initial management strategy for chronic CAD