1. Ten Year Outcome of Coronary Artery Bypass Graft Surgery Versus Medical Therapy in Patients with Ischemic Cardiomyopathy Results of the Surgical Treatment for Ischemic Heart Failure Extension Study

2. Background Advances in the management of coronary artery disease and heart failure have increased survival for patients with severe left ventricular systolic dysfunction. Whether surgical revascularization leads to improved survival beyond guideline directed medical therapy (MED) remains controversial. Previously, at a median of 56-month follow-up, we reported that CABG added to MED led to a reduction in all cause death which did not reach statistical significance. (Velazquez EJ et al. N Engl J Med 2011)

3. Surgical Treatment for Ischemic Heart Failure Extension Study In patients with HF and LVD who have CAD amenable to CABG, surgical revascularization combined with guideline- directed medical therapy (MED) will decrease all-cause mortality compared to MED alone at ~10 years

4. Study Design RCT, non-blinded  CABG + MED vs. MED alone 99 clinical sites in 22 countries Investigator-initiated and led NHLBI funded Independent Data Safety Monitoring Committee Blinded Clinical Events Adjudication Committee

5. Endpoints Primary Endpoint  All-cause mortality Major Secondary Endpoints  Cardiovascular mortality  Death (all-cause) + cardiovascular hospitalization

6. Important Inclusion Criteria LVEF ≤ 0.35 within 3 months of trial entry CAD suitable for CABG MED eligible  Absence of left main CAD as defined by an intraluminal stenosis of ≥ 50%  Absence of CCS III angina or greater (angina markedly limiting ordinary activity)

7. Major Exclusion Criteria Recent acute MI (within 30 days) judged to be an important cause of LVD Cardiogenic shock (within 72 hours of randomization) Plan for percutaneous intervention of CAD Aortic valve disease clearly indicating the need for aortic valve repair or replacement

8. Study Conduct Randomization 1,212 Subjects Randomized MED n = 602 CABG + MED n = 610 Final status for all patients was 98% complete at the final follow-up period June through end of November 2015. Median follow-up of 9.8 years; Max follow-up 13.4 years Age (median) 60 years; 12% women Prior MI 77%; Diabetes 39% Baseline NYHA II-IV 89% LVEF 28% and ESVI 78 ml/m 2 (median) Multi-vessel disease 74%; Proximal LAD 68%

9. Study Conduct Randomization 1,212 Subjects Randomized MED n = 602 CABG + MED n = 610 Final Analysis Median Follow-up 9.8 yrs. Max. Follow-up 13.4 yrs. n = 12 Withdrew or lost Analyzed n = 602 (100%) Analyzed n = 610 (100%) n = 13 Withdrew or lost

10. CABG Conduct Variable Randomized to CABG (N=610) CABG received — no (%)555 (91) Time to CABG, days — Median (IQR)10 (5, 16) Performed electively — %95 Arterial conduits ≥ 1, %91 Total conduits ≥ 3, %56

11. Medication Use All Patients Randomized (N=1212) MedicationBaseline Last Follow-Up Aspirin or clopidogrel, %8685 ACE inhibitor or ARB, %9084 Beta-blocker, %8588 Statin, %8185 Loop Diuretics, %6572 K+ Sparing Diuretics, %4653

12. All-cause Mortality 0.28 at 3 years 0.41 at 5 years 0.68 at 10 years

13. All-cause Mortality NNT = 14

14. Cardiovascular Mortality NNT = 11

15. All-cause Mortality or Cardiovascular Hospitalization

16. Other Outcomes Outcomes CABG (N=610) MED (N=602) Hazard Ratio (95% CI) (CABG vs. MEDP-value Death or heart failure hospitalization 404 (66.2%) 450 (74.8%) 0.81 (0.71, 0.93)0.002 Death or all-cause hospitalization 506 (83.0%) 538 (89.4%) 0.81 (0.71, 0.91)0.001 Death or revascularization (PCI or CABG) 388 (63.6%) 478 (79.4%) 0.63 (0.55, 0.73)<0.001 Death or non-fatal myocardial infarction 376 (61.6%) 409 (67.9%) 0.86(0.74, 0.98)0.032 Death or non-fatal stroke367 (60.2%) 406 (67.4%) 0.85 (0.74, 0.98)0.032

17. Conclusions Among patients with ischemic cardiomyopathy, CABG significantly decreased the long-term rates of  death from any cause  death from cardiovascular causes  death or cardiovascular hospitalization  death or HF hospitalization  death or revascularization  death or non-fatal MI  death or non-fatal stroke

18. Implications Severe left ventricular dysfunction should prompt an evaluation for the extent and severity of angiographic CAD. Among patients with ischemic cardiomyopathy, CABG should be strongly considered to improve long-term survival.

19. Recognition Thank you to the STICH global network of investigators and coordinators and the NHLBI for its long-term support Thank you to all STICH patients and their families

21. Back Up Slides

22. Baseline Characteristics VariableMED (N=602)CABG(N=610) Age, median (IQR), yrs59 (53, 67) 60 (54, 68) Female, %12 Black or other, % 3033 Myocardial infarction, %7876 Diabetes, %4039 Previous PCI or CABG, %1416 NYHA HF Class I, %1211 NYHA HF Class II, %5152 NYHA HF Class III/IV, %37 No Angina — no. (%)3736 CCS Angina Class I, % 1516 CCS Angina Class > II, %48

23. Baseline Characteristics Variable MED (N=602) CABG (N=610) Left ventricular ejection fraction (%) — median2827 End Systolic Volume Index, mL/m 2 - median7779 Mitral Regurgitation (≥ 2+), %63 Coronary anatomy No. of vessels with ≥ 75% stenosis — % 0-12624 238 33637 Proximal LAD6967

24. Medication Use MED (N=602) CABG (N=610) MedicationBaseline Last Follow-UpBaseline Last Follow-Up Aspirin513 (85)466 (82)489 (80)449 (82) Aspirin or clopidogrel533 (89) 486 (86) 509 (83)467 (85) ACE inhibitor or ARB531 (88)483 (85)554 (91)456 (83) Beta-blocker529 (88)500 (88)507 (83)477 (87) Statin500 (83)478 (84)483 (79)471 (86) Loop Diuretics392 (65)400 (71)399 (66)404 (73) K+ Sparing Diuretics276 (46)300 (53)280 (46)297 (54)

25. All-cause Mortality as Treated

26. All-cause Mortality per Protocol

27. Subgroup Analysis on All-cause Mortality

28. Subgroup Analysis on All-cause Mortality (continued)