Transcript Velazquez_STICHESx - Clinical Trial Results

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
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)
Surgical Treatment for Ischemic
Heart Failure Extension Study
In patients with HF and LVD who have CAD
amenable to CABG, surgical
revascularization combined with guidelinedirected medical therapy (MED) will
decrease all-cause mortality compared to
MED alone at ~10 years
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
Endpoints
• Primary Endpoint
 All-cause mortality
• Major Secondary Endpoints
 Cardiovascular mortality
 Death (all-cause) + cardiovascular
hospitalization
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)
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
Study Conduct
1,212 Subjects
Randomized
CABG + MED
n = 610
Randomization
MED
n = 602
Final status for all patients was 98% complete at the
•final
Age
(median)
60 years;
12% women
follow-up
period
June through
end of
•November
Prior MI2015.
77%; Diabetes 39%
• Baseline NYHA II-IV 89%
2 (median)
•Median
LVEFfollow-up
28% andofESVI
78
ml/m
9.8 years; Max follow-up 13.4
•years
Multi-vessel disease 74%; Proximal LAD 68%
Study Conduct
1,212 Subjects
Randomized
CABG + MED
n = 610
Randomization
n = 12
Withdrew or lost
n = 13
Withdrew or lost
Analyzed
n = 610 (100%)
MED
n = 602
Final Analysis
Median Follow-up 9.8 yrs.
Max. Follow-up 13.4 yrs.
Analyzed
n = 602 (100%)
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
Medication Use
All Patients Randomized
(N=1212)
Baseline
Last
Follow-Up
Aspirin or clopidogrel, %
86
85
ACE inhibitor or ARB, %
90
84
Beta-blocker, %
85
88
Statin, %
81
85
Loop Diuretics, %
65
72
K+ Sparing Diuretics, %
46
53
Medication
All-cause Mortality
0.68
at 10 years
0.41
at 5 years
0.28
at 3 years
All-cause Mortality
NNT = 14
Cardiovascular Mortality
NNT = 11
All-cause Mortality or
Cardiovascular Hospitalization
Other Outcomes
CABG
(N=610)
MED
(N=602)
Hazard Ratio (95% CI)
(CABG vs. MED
P-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 stroke
367
(60.2%)
406
(67.4%)
0.85 (0.74, 0.98)
0.032
Outcomes
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
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.
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
Back Up Slides
Baseline Characteristics
Variable
MED (N=602)
CABG(N=610)
59 (53, 67)
60 (54, 68)
Female, %
12
12
Black or other, %
30
33
Myocardial infarction, %
78
76
Diabetes, %
40
39
Previous PCI or CABG, %
14
16
NYHA HF Class I, %
12
11
NYHA HF Class II, %
51
52
NYHA HF Class III/IV, %
37
37
No Angina — no. (%)
37
36
CCS Angina Class I, %
15
16
CCS Angina Class > II, %
48
48
Age, median (IQR), yrs
Baseline Characteristics
MED
(N=602)
CABG
(N=610)
Left ventricular ejection fraction (%) — median
28
27
End Systolic Volume Index, mL/m2 - median
77
79
Mitral Regurgitation (≥ 2+), %
63
63
0-1
26
24
2
38
38
3
36
37
Proximal LAD
69
67
Variable
Coronary anatomy
No. of vessels with ≥ 75% stenosis — %
Medication Use
MED (N=602)
CABG (N=610)
Medication
Baseline
Last
Follow-Up
Baseline
Last
Follow-Up
Aspirin
513 (85)
466 (82)
489 (80)
449 (82)
Aspirin or clopidogrel
533 (89)
486 (86)
509 (83)
467 (85)
ACE inhibitor or ARB
531 (88)
483 (85)
554 (91)
456 (83)
Beta-blocker
529 (88)
500 (88)
507 (83)
477 (87)
Statin
500 (83)
478 (84)
483 (79)
471 (86)
Loop Diuretics
392 (65)
400 (71)
399 (66)
404 (73)
K+ Sparing Diuretics
276 (46)
300 (53)
280 (46)
297 (54)
All-cause Mortality as Treated
All-cause Mortality per Protocol
Subgroup Analysis
on All-cause Mortality
Subgroup Analysis
on All-cause Mortality (continued)