1. Financial Disclosures March 31, 2009 Daniel B. Mark, MD, MPH Professor of Medicine Director, Outcomes Research Duke University Medical Center Duke Clinical Research Institute Financial Disclosures ConsultingAventis Astra Zeneca Medtronic, Inc. Novartis Research Grants NIH Proctor & Gamble Pfizer Medtronic, Inc. Alexion Pharmaceuticals MedicureInnocoll St. Jude

2. Quality of Life and Economic Outcomes with Surgical Ventricular Reconstruction in Symptomatic Heart Failure March 31, 2009 Daniel B. Mark, MD, MPH Duke Clinical Research Institute On behalf of the STICH Economics and Quality of Life Research Team and the STICH Investigators Economics and Quality of Life portion of STICH supported by NHLBI

3. The Surgical Treatment of Ischemic Heart Failure (STICH) Research Program: Background of SVR Trial Subset of ischemic cardiomyopathy pts develop progressive HF due to adverse LV remodelingSubset of ischemic cardiomyopathy pts develop progressive HF due to adverse LV remodeling Surgical ventricular reconstruction (SVR) is novel procedure to LV size, create more normal LV shapeSurgical ventricular reconstruction (SVR) is novel procedure to LV size, create more normal LV shape Observational studies of SVR have shown improvement in HF symptoms and QOLObservational studies of SVR have shown improvement in HF symptoms and QOL Since SVR almost always done with CABG, unclear what specific incremental benefits the procedure provides. Also, economics of procedure unknown.Since SVR almost always done with CABG, unclear what specific incremental benefits the procedure provides. Also, economics of procedure unknown.

4. STICH 1° Hypothesis and Design Overview 1° Hypothesis: Adding SVR to CABG in ischemic HF pts will death/ cardiac rehospitalization 1000 HF pts (2002-2006) CAD, EF.35, anterior LV wall scar amenable to SVR 499 CABG only 501 CABG + SVR 7% did not receive operation7% did not receive operation 9% did not receive operation9% did not receive operation Median follow-up 48 months

5. EQOL STICH Baseline Characteristics CABG only (n=499)6216%10% 7% 45% 42% 6% 87%35% CABG + SVR (n=501)6214%8% 10% 41% 44% 5% 87%34% Age (mean) Female Race, nonwhite Current NYHA Class I II III IV Previous MI Diabetes

6. STICH 1° Composite Endpoint: Death or Cardiac Rehospitalization Jones RH et al. NEJM 09

7. STICH Economics and Quality of Life Study: Key Questions Does SVR added to CABG significantly improve functioning and well-being in ischemic heart failure?Does SVR added to CABG significantly improve functioning and well-being in ischemic heart failure? What are the economic implications of adding SVR to CABG in patients with ischemic heart failure?What are the economic implications of adding SVR to CABG in patients with ischemic heart failure?

8. EQOL STICH: Quality of Life (QOL) Methods Overview QOL structured interviews at baseline and 4, 12, 24, and 36 months post- randomizationQOL structured interviews at baseline and 4, 12, 24, and 36 months post- randomization 991 (99%) of 1000 main STICH pts in QOL991 (99%) of 1000 main STICH pts in QOL 4136 (92%) expected QOL contacts collected4136 (92%) expected QOL contacts collected

9. EQOL STICH: Selected QOL Assessment Instruments Instrument Kansas City Cardiomyopathy Questionnaire (KCCQ) Seattle Angina Questionnaire SF-36 scales, SF-12 Center for Epidemiologic Studies -Depression (CES-D) Scale Euro-QoL 5D QOL Domain Heart Failure-specific health status Angina symptoms Psychological well-being (MHI-5), role function, social function, vitality, overall health status Depressive symptoms Patient utilities

10. Kansas City Cardiomyopathy Questionnaire (KCCQ): Overview 23-item disease specific QOL assessment instrument23-item disease specific QOL assessment instrument Used to measure effects of heart failure symptoms on functional limitations, social limitations, self efficacy, and patient satisfaction with overall QOLUsed to measure effects of heart failure symptoms on functional limitations, social limitations, self efficacy, and patient satisfaction with overall QOL Overall summary score plus 6 component scoresOverall summary score plus 6 component scores Scores 1-100 (higher=better), difference > 5 points clinically significantScores 1-100 (higher=better), difference > 5 points clinically significant Green CP JACC 2000 Spertus J AHJ 2005

11. STICH QOL 1 Outcome: KCCQ Overall Summary Score P=.26 P=.76P=.89 CABG CABG + SVR KCCQ Overall Summary (0-100) Score 0-100 higher = better P=.53 Clinically significant > 5 points > 5 points P=.89

12. STICH QOL Outcomes: KCCQ Quality of Life Satisfaction Score P=.47 P=.87P=.84 KCCQ QOL Score (0-100) Score 0-100 higher = better P=.70 Clinically significant > 5 points > 5 points P=.82 CABG CABG + SVR

13. STICH QOL Outcomes: Seattle Angina Questionnaire- Frequency P=.74P=.77P=.46 SAQ Angina Frequency (0-100) Score 0-100 higher =lower freq P=.01 Clinically significant > 5 points > 5 points P=.27 CABG CABG + SVR

14. STICH QOL Outcomes: CES-D Depression Scale P=.42P=.41P=.25 % Depressed P=.40 P=.25 CABG CABG + SVR

15. STICH QOL Outcomes: Other Secondary Comparisons by ITT No treatment-related difference in: Additional KCCQ subscales Additional SAQ scales SF-12 Physical and Mental Components SF-36 subscales Cardiac Self-Efficacy 0-100 self rating Euro-QoLNo treatment-related difference in: Additional KCCQ subscales Additional SAQ scales SF-12 Physical and Mental Components SF-36 subscales Cardiac Self-Efficacy 0-100 self rating Euro-QoL

16. STICH Economic Substudy: Methods Overview Resource use data from CRF and medical billsResource use data from CRF and medical bills Bills collected on 196 of 200 (98%) U.S. patientsBills collected on 196 of 200 (98%) U.S. patients Costs estimated using hospital bills, Medicare correction factors, and Medicare fee scheduleCosts estimated using hospital bills, Medicare correction factors, and Medicare fee schedule Outpatient care, medications, productivity costs, non-medical costs not includedOutpatient care, medications, productivity costs, non-medical costs not included Cost effectiveness not performed (SVR arm not clinically superior to CABG alone)Cost effectiveness not performed (SVR arm not clinically superior to CABG alone) Results reported in 2008 US$Results reported in 2008 US$

17. STICH Economic Substudy: Selected Medical Resource Use in US Cohort by ITT CABG 5.7 hours 5.7 hours 3.4 days 6.0 days 9.5 days 13.5 days CABG + SVR 6.8 hours 7.6 days 9.9 days 13.4 days 16.8 days Resource Use OR time OR time Post-op time in ICU/CCU Post-op time in ICU/CCU Total ICU time Total ICU time Post-op LOS Post-op LOS Total LOS Total LOS P-value<0.001<0.0010.0002<0.0010.03

18. STICH Economic Substudy: Selected ICU Medical Resource Use in US Cohort by ITT CABG 17.8% 17.8%11.9%38.6% CABG + SVR 27.6%32.7%62.2% Other Resource Use PA catheter PA catheter IABP for low CO IABP for low CO Inotropes for low CO Inotropes for low CO P-value0.100.00030.0008

19. STICH Economic Substudy: Index Hospitalization Costs in US Cohort by ITT $50,939 $ 5,183 $64,202 $ 6,515$56,122 $70,717 2008 US Dollars P=0.004 Index Hosp Physician Fees

20. EQOL STICH: Limitations Unblinded treatment assignment, participation in RCT may distort careUnblinded treatment assignment, participation in RCT may distort care Resource use and cost patterns seen in the U.S. cohort do not reflect patterns in other participating countriesResource use and cost patterns seen in the U.S. cohort do not reflect patterns in other participating countries

21. STICH Economic and Quality of Life Outcomes: Summary STICH is first RCT comparing 2 cardiac surgical treatment strategiesSTICH is first RCT comparing 2 cardiac surgical treatment strategies Adding SVR to CABG does not provide any incremental improvements in QOL out to 3 years post-surgeryAdding SVR to CABG does not provide any incremental improvements in QOL out to 3 years post-surgery SVR complexity of post-operative care and significantly costs of the procedure over CABG aloneSVR complexity of post-operative care and significantly costs of the procedure over CABG alone No benefit for continued routine use of this procedure in STICH-eligible ptsNo benefit for continued routine use of this procedure in STICH-eligible pts

22. American Heart Journal 2009 March 31;0:1-8.e3.