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

Quality of Life and Economic Outcomes with Surgical Ventricular Reconstruction in Symptomatic Heart Failure 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 March 31, 2009

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 remodeling Surgical 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 QOL Since SVR almost always done with CABG, unclear what specific incremental benefits the procedure provides. Also, economics of procedure unknown.

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 Median follow-up 48 months 7% did not receive operation 9% did not receive operation

EQOL STICH Baseline Characteristics Age (mean) Female Race, nonwhite Current NYHA Class I II III IV Previous MI Diabetes CABG only (n=499) 62 16% 10% 7% 45% 42% 6% 87% 35% CABG + SVR (n=501) 62 14% 8% 10% 41% 44% 5% 87% 34%

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

STICH Economics and Quality of Life Study: Key Questions 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?

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

EQOL STICH: Selected QOL Assessment Instruments 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

Kansas City Cardiomyopathy Questionnaire (KCCQ): Overview 23-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 QOL Overall summary score plus 6 component scores Scores 1-100 (higher=better), difference > 5 points clinically significant Green CP JACC 2000 Spertus J AHJ 2005

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

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

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

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

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-QoL

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

STICH Economic Substudy: Selected Medical Resource Use in US Cohort by ITT OR time Post-op time in ICU/CCU Total ICU time Post-op LOS Total LOS CABG 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 P-value <0.001 0.0002 0.03

STICH Economic Substudy: Selected ICU Medical Resource Use in US Cohort by ITT Other Resource Use PA catheter IABP for low CO Inotropes for low CO CABG 17.8% 11.9% 38.6% CABG + SVR 27.6% 32.7% 62.2% P-value 0.10 0.0003 0.0008

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

EQOL STICH: Limitations Unblinded 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 countries

STICH Economic and Quality of Life Outcomes: Summary STICH 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-surgery SVR ↑ 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 pts

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