1. Revascularization in Patients With Left Ventricular Dysfunction:
Lessons From STICH
Robert O. Bonow, MD, MS
Northwestern University Feinberg School of Medicine
Bluhm Cardiovascular Institute
Northwestern Memorial Hospital
Editor-in-Chief
JAMA Cardiology
No Relationships to Disclose

2. Prognosis in Chronic CAD Influence of LV Ejection Fraction80
74%
65%
62% 60
56%
50%
10 Year Survival Rate (%) 40
27% 20
Medical Surgical
Medical Surgical
Medical Surgical
EF >50%
EF 35-50%
EF <35%
from Muhlbaier et al, Circulation 1992;86:II-198

3. Prognosis in Chronic CAD Influence of LV Ejection Fraction
100
EF >50% 80
EF 35-49% 60
Survival (percent) 40
EF <35% 20
p<0.001 2 4 6 8 10 12 14
Years
Emond et al, Circulation 1994;90:

4. Prognosis in Chronic CAD Effect of Revasularization
100
Patients with EF <35% 80
CABG 60
Survival (percent) 40
Medical 20
p<0.001 1 2 3 4 5 6
Years
Alderman et al, Circulation 1983;68:

5. Prognosis in Ischemic LV Dysfunction
Increase in Survival by Revascularization 60
57%
55% 50
44%
41% 40
37%
30%
Increase in Survival (%) 30 20
10% 10
Vliestra
Alderman
Manley
Pigott
Bounous
Faulkner
1977
1983
Muhlbaier
1976
1992
1985
1988
1977

6. Prognosis in Ischemic LV Dysfunction
Increase in Survival by Medical Therapy
100
90%
[70,96] 80
77%
[43,91] 60
Increase in Survival (%) 40
38%
[20,68] 20
ACEi / ARB
ACEi / ARB
+ β blocker
ACEi / ARB
+ β blocker
+ ICD / CRT
from Yancy CW, J Am Heart Assoc 2012;1:16-26

7. Surgical Treatment for Ischemic Heart Failure

8. STICH Trial 1212 patients with EF <35% 99 sites in 22 countries
Primary Endpoint:
All-cause mortality
Secondary Endpoints:
CV mortality
Death + CV hospitalization

9. STICH Trial Median age 59 years Median LVEF 29% Men 88% Diabetes 40%
Prior heart failure 95%
Prior PCI or CABG 12%

10. Years After Randomization
STICH Primary Outcome
All-Cause Mortality
0.8
Medical therapy
CABG
1212 patients
EF <35%
0.6
HR % CI
P = 0.123
Medical therapy
Mortality Rate
0.4
CABG
0.2 1 2 3 4 5 6
Years After Randomization
Velazquez et al. N Engl J Med 2011;364:

11. STICH Secondary Outcome
Cardiovascular Mortality
0.8
Medical therapy
CABG
1212 patients
EF <35%
0.6
HR % CI
P = 0.050
CV Mortality Rate
0.4
Medical therapy
CABG
0.2 1 2 3 4 5 6
Years After Randomization
Velazquez et al. N Engl J Med 2011;364:

12. STICH Secondary Outcome
Death + CV Hospitalization
0.8
Medical therapy
CABG
Medical therapy
0.6
HR % CI
CABG
P <0.001
Death or CV Hospitalization
0.4
0.2 1 2 3 4 5 6
Years After Randomization
Velazquez et al. N Engl J Med 2011;364:

13. 1212 602 610 Randomized medicine Randomized CABG
Velazquez et al. N Engl J Med 2011;364:

14. 1212 602 610 592 537 55 Randomized medicine Randomized CABG Received
Velazquez et al. N Engl J Med 2011;364:

15. 1212 602 610 592 620 537 555 55 18 Randomized medicine Randomized CABG
Received
medicine
Received
CABG
592
620
Velazquez et al. N Engl J Med 2011;364:

16. STICH Secondary Outcome
All-Cause Mortality – Treatment Received
0.8
Medical therapy
CABG
0.6
HR % CI
,0.84
Medical therapy
P <0.001
Mortality Rate
0.4
CABG
0.2 1 2 3 4 5 6
Years After Randomization
Doenst et al. Circ Heart Fail 2013;6:
Velazquez et al. N Engl J Med 2011;364:

17. STICH Secondary Outcome
All-Cause Mortality – Per Protocol
0.8
Medical therapy
CABG
0.6
HR % CI
,0.92
Medical therapy
P = 0.005
Mortality Rate
0.4
CABG
0.2 1 2 3 4 5 6
Years After Randomization
Doenst et al. Circ Heart Fail 2013;6:
Velazquez et al. N Engl J Med 2011;364:

18. Is STICH a negative trial or a positive trial?
STICH Quality of LIfe
KCCQ: Overall Summary
KCCQ Overall Summary 80
CABG + Medical
CABG 75
Medical alone
Medical 70 65
Is STICH a negative trial or a positive trial? 60
Baseline
4 mo
12 mo
24 mo
36 mo
Mark et al, Ann Intern Med 2014;161:

19. Myocardial Revascularization in Patients with LV Dysfunction
The STICH Trial:
Are there subsets who benefit from CABG?
Myocardial viability

20. Myocardial Revascularization in Patients with LV Dysfunction
The STICH Trial:
Are there subsets who benefit from CABG?
Myocardial viability
0.8
Without Viability
With Viability
MED (33 deaths)
0.56
MED (95 deaths)
0.6
CABG (25 deaths)
CABG (83 deaths)
0.35
0.4
Mortality Rate
0.42
0.31
0.2
Interaction
P value
0.528 1 2 3 4 5 6 1 2 3 4 5 6
Years Following Randomization
Years Following Randomization
Bonow et al. N Engl J Med 2011;364:

21. Myocardial Revascularization in Patients with LV Dysfunction
The STICH Trial:
Are there subsets who benefit from CABG?
Myocardial viability
The Heart Trial
0.8
With Viability
With Viability
Medical therapy (n=69)
MED (95 deaths)
0.6
Revascularization (n=69)
CABG (83 deaths)
0.35
0.4
n=138
Mortality Rate
p=NS
0.31
0.2 1 2 3 4 5 6 1 2 3 4 5 6
Years Following Randomization
Years Following Randomization
from Cleland et al, Eur J Heart Fail 2011;13:
Bonow et al. N Engl J Med 2011;364:

22. Patients with ESVI ≤84 ml/m2
Bonow et al, JACC Cardiovasc Imaging 2015;8:

23. Patients with ESVI >84 ml/m2
Bonow et al, JACC Cardiovasc Imaging 2015;8:

24. Revascularization vs Medical Therapy
in Patients with Left Ventricular Dysfunction 80
n=306
p=NS 60
Medical
3-Year Mortaltiy (%) 40
Revascularization 20 10 20 30 40 50
Amount of Compromised Viable Myocardium (%)
from Tarakji et al, Circulation 2006;113:

25. Myocardial Revascularization in Patients with LV Dysfunction
The STICH Trial:
Are there subsets who benefit from CABG?
Myocardial ischemia

26. Myocardial Revascularization in Patients with LV Dysfunction
The STICH Trial:
Are there subsets who benefit from CABG?
Myocardial ischemia
No Ischemia
Ischemia
0.6
MED (31 deaths)
MED (56 deaths)
CABG (22 deaths)
CABG (47 deaths)
0.39
0.39
0.4
Mortality Rate
0.35
0.33
0.2 1 2 3 4 5 6 1 2 3 4 5 6
Years Following Randomization
Years Following Randomization
Panza et al. J Am Coll Cardiol 2013;61:

27. Total myocardium ischemic (%)
Impact of Ischemia and Scar on Therapeutic Benefit of Coronary Revascularization
N=13,555
Medical therapy
Log hazard ratio
Revascularization
P<0.001
Magnitude of ischemic myocardium associated with survival benefit with revascularization in patients without prior MI
No such benefit in patients with prior MI
Role of ischemia not significant in patients with >10% myocardial scar
Total myocardium ischemic (%)
Hachamovich et al, Eur Heart J 2011;32:

28. Myocardial Revascularization in Patients with LV Dysfunction
The STICH Trial:
Are there subsets who benefit from CABG?
Functional capacity
PAS >55 + 6MW ≥300m
PAS ≤55 + 6MW <300m
0.6
MED
MED
CABG
CABG
0.39 HR
95% CI
P value HR
95% CI
P value
0.4
0.71
0.52,0.97
0.033
0.95
0.75,1.19
0.626
Mortality Rate
P=0.033
P=0.626
0.33
0.2 1 2 3 4 5 6 1 2 3 4 5 6
Years Following Randomization
Years Following Randomization
Stewart et al. JACC Heart Fail 2014;2:

29. Myocardial Revascularization in Patients with LV Dysfunction
The STICH Trial:
Are there subsets who benefit from CABG?
CAD severity, EF, ESV
0.8
2 – 3 Factors
0 – 1 Factor
MED (31 deaths)
MED (56 deaths)
0.6
CABG (22 deaths)
0.51
CABG (47 deaths)
0.39
0.39 HR
95% CI
P value HR
95% CI
P value
0.4
0.71
0.36,0.89
0.033
1.08
0.81,1.44
0.626
Mortality Rate
0.30
P=0.0004
0.39
P=0.591
0.35
0.33
0.2
0.30 1 2 3 4 5 6 1 2 3 4 5 6
Years Following Randomization
Years Following Randomization
Panza et al. J Am Coll Cardiol 2014;64:

30. Myocardial Revascularization in Patients with LV Dysfunction
Factors to consider:
• Severity of LV dysfunction
• Severity of LV remodeling
• Angiographic severity of CAD
• Functional capacity
• Extent of myocardial viability
• Severity of myocardial ischemia
• Biomarkers \
More important
Less important
Velazquez and Bonow. J Am Coll Cardiol 2015;65:

31. STICHES (STICH Extention)
1212 patients with EF <35%
Mean follow-up 9.8 years
Final ascertainment in 98%
Primary Endpoint:
All-cause mortality
Secondary Endpoints:
CV mortality
Death + CV hospitalization

32. Years After Randomization
STICH Primary Outcome
All-Cause Mortality
0.8
Medical therapy
CABG
1212 patients
EF <35%
0.6
Medical therapy
Mortality Rate
0.4
CABG
HR % CI
0.2
P = 0.123 2 4 6 8 10
Years After Randomization
Velazquez et al. N Engl J Med 2011;364:

33. STICHES Primary Outcome Years After Randomization
All-Cause Mortality
0.8
Medical therapy
CABG
1212 patients
EF <35%
0.6
HR % CI
Medical therapy
Mortality Rate
0.4
CABG
HR % CI
0.2
P = 0.020 2 4 6 8 10
Years After Randomization
Velazquez et al. N Engl J Med 2016;374:

34. STICHES Secondary Outcome
Cardiovascular Mortality
0.8
Medical therapy
CABG
1212 patients
EF <35%
0.6
HR % CI
Medical therapy
Mortality Rate
0.4
CABG
HR % CI
0.2
P = 0.006 2 4 6 8 10
Years After Randomization
Velazquez et al. N Engl J Med 2016;374:

35. STICHES Secondary Outcome
All-Cause Mortality – Treatment Received
0.8
Medical therapy
CABG
1212 patients
EF <35%
0.6
HR % CI
Medical therapy
Mortality Rate
0.4
CABG
HR % CI
0.2
P < 0.001 2 4 6 8 10
Years After Randomization
Velazquez et al. N Engl J Med 2016;374:

36. STICHES Secondary Outcome
Death + CV Hospitalization
1.0
Medical therapy
CABG
1212 patients
EF <35%
0.8
Medical therapy
0.6
CABG
Mortality Rate
0.4
HR % CI
0.2
P < 0.001 2 4 6 8 10
Years After Randomization
Velazquez et al. N Engl J Med 2016;374:

37. Implications of STICH Extention Study
Patients with HF and CAD remain at substantial risk despite excellent medical adherence % 10-year mortality risk
CABG added to medical therapy leads to a robust, durable reduction in all-cause mortality
Number needed to treat:
To prevent 1 death = 14 patients
To prevent 1 CV death = 11 patients
Among patients with HF and LVD, a diagnostic approach to evaluate the extent and severity of CAD and potential for CABG should be strongly considered