Eric J. Velazquez, MD on behalf of the STICH Investigators
April 4, 2011

STICH Financial Disclosures
Original Recipient Institution Principal
Investigator
Duke University Medical Center Robert H. Jones
Duke University Medical Center Kerry L. Lee
Duke University Medical Center Daniel B. Mark
Univ of Alabama-Birmingham
Mayo Clinic
University of Pittsburgh
Northwestern University
Gerald M. Pohost
Jae K. Oh
Arthur M. Feldman
Robert O. Bonow
Washington Hospital Center Julio A. Panza
Baylor University Medical Center Paul Grayburn
Activity
Funding Sources:
National Heart, Lung and Blood Institute 97.7%
Abbott Laboratories 2.3%
Clinical Coordinating Ctr
Statistical and Data CC
EQOL Core Laboratory
CMR Core Laboratory
ECHO Core Laboratory
NCG Core Laboratory
RN Core Laboratory
DECIPHER Substudy
MR TEE Substudy

Background — I
• Coronary artery disease (CAD) is a major substrate for heart failure (HF) and left ventricular dysfunction (LVD).
• The role of coronary artery bypass graft surgery (CABG) in patients with CAD and
HF has not been clearly established.

Background — II
• In the 1970s, RCTs of CABG vs. medical therapy for chronic stable angina excluded patients with severe LVD
 Only 4.0% symptomatic with HF
• Major advances in surgical care and medical therapy (MED) render previous data obsolete for clinical decision making
• Observational analyses suggest a role for CABG for HF and LVD
 CABG is increasingly utilized for these patients
 Yet, substantial clinical uncertainty remains

Surgical Treatment for Ischemic Heart
Failure Trial (STICH)
Surgical Revascularization Hypothesis
In patients with HF, LVD and CAD amenable to surgical revascularization, CABG added to intensive MED will decrease all-cause mortality compared to MED alone.

Study Design
• Randomized controlled trial, non-blinded
• Investigator-initiated and led
• National Heart, Lung and Blood Institute funded
• Duke Clinical Research Institute managed
• Independent Data and Safety Monitoring Committee
• Clinical Events Adjudication Committee
• Blinded Core Laboratories

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

Statistical Assumptions and Analyses
Statistical Assumptions
• MED mortality of 25% at
3 years
• CABG would reduce mortality by 25%
• 20% or fewer crossovers from MED to CABG
• 400 or more deaths
• 90% power
Planned Analyses
• Intention to treat
(as randomized)
• Covariate-adjusted
• As treated
 Time-dependent
• Per protocol

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)
• Cardiogenic shock (within 72 hours of randomization)
• Plan for percutaneous intervention
• Aortic valve disease requiring valve repair or replacement
• Non-cardiac illness with a life expectancy of less than 3 years or imposing substantial operative mortality

STICH Revascularization Hypothesis
1212
Randomized
MED only
602
• 99 clinical sites in 22 countries
• Enrollment: July 2002 – May 2007
610
Randomized
CABG

Selected Baseline Characteristics
Variable
Age, median (IQR), yrs
Female, %
Diabetes, %
Prior Myocardial infarction, %
Prior Heart Failure within 3 months, %
Prior PCI or CABG, %
LVEF (%) — median
Multi-vessel disease (>50%), %
Proximal LAD stenosis (>75%), %
MED (N=602)
59 (53, 67)
12
40
78
95
15
28
91
69
CABG (N=610)
60 (54, 68)
12
39
76
94
16
27
91
67

Medical Therapy
Medication, %
Aspirin
Aspirin or warfarin
ACE inhibitor or ARB
Beta-blocker
Statin
K+ sparing diuretic
ICD
MED (N=602) CABG (N=610)
Baseline
Latest
Follow-up Baseline
Latest
Follow-up
85
91
88
84
93
89
80
84
91
84
92
89
88
83
46
2
90
87
53
19
83
79
46
2
90
90
54
15

CABG Conduct
Variable
CABG received — no (%)
Time to CABG, days — Median (IQR)
Performed electively, %
Arterial conduits ≥ 1, %
Venous conduits ≥ 1, %
Total grafts ≥ 2, %
Length of stay, days — Median (IQR)
CABG
(N=610)
555 (91)
10 (5, 16)
95
91
86
88
9 (7, 13)

Patient Follow-up
• Last follow-up period: August – November 2010
• Final follow-up ascertained: 1207 (99.6%)
 Only 5 patients were not evaluable with median follow-up of 40 months
• Overall duration of follow-up: 56 months

All-Cause Mortality
— As Randomized
HR 0.86 (0.72, 1.04)
P = 0.123
0.46
0.41

All-Cause Mortality
— As Randomized
HR 0.86 (0.72, 1.04)
P = 0.123
Adjusted HR 0.82 (0.68, 0.99)
Adjusted P = 0.039
0.46
0.41

Cardiovascular Mortality
— As Randomized
HR 0.81 (0.66, 1.00)
P = 0.050
Adjusted HR 0.77 (0.62, 0.94)
Adjusted P = 0.012
0.39
0.32

Death or Cardiovascular
Hospitalization — As Randomized
HR 0.74 (0.64, 0.85)
P < 0.001
Adjusted HR 0.70 (0.61, 0.81)
P < 0.001
0.68
0.58

Time-varying Hazard Ratios
— As Randomized

STICH Revascularization Hypothesis
Treatment As Received
1212
Randomized
MED only
602 17% 9% 610
Randomized
CABG
537
Received
MED only
55 65 555
Received
CABG
As treated MED (592) vs. CABG (620)

All-Cause Mortality
— As Treated
HR 0.70 (0.58 – 0.84)
P < 0.001
0.49
0.38

STICH Revascularization Hypothesis
Treatment Per Protocol
1212
Randomized
MED only
602 17% 9% 610
Randomized
CABG
537
Received
MED only
55 65 555
Received
CABG
Per protocol: MED (537) vs. CABG (555)

All-Cause Mortality
— Per Protocol
HR 0.76 (0.62, 0.92)
P = 0.005
0.48
0.37

Limitations
• The adjusted, as treated and per protocol analyses of the primary endpoint although informative should be considered provisional
• The STICH trial was not blinded and nonfatal outcomes could have been influenced by the knowledge of the treatment received

Summary
• We compared CABG with contemporary evidence-based MED alone among high-risk patients with CAD, HF and LVD
• Despite the medical adherence and operative results achieved, STICH-like patients remain at substantial risk
 5-year mortality risk with MED only = 40%

Conclusions
• In patients randomized to STICH, there was no statistically significant difference in allcause mortality between medical therapy alone and medical therapy with CABG
• Medical therapy with CABG reduces cardiovascular mortality and morbidity compared to medical therapy alone
• When randomized to CABG, patients are exposed to an early risk

Clinical Implications
• CAD should be assessed and medical therapy optimized for all patients presenting with HF.
• Decision making for CABG is complex, should be individualized and take into account the short-term risk for long-term benefit.
• The STICH Extension Study will test the durability of these results at 10 years.

THANK YOU
Thank you to the STICH Investigators and
Coordinators
…and the STICH patients without whose participation in clinical research the STICH trial would never have been completed

Full report available online at NEJM.org