1. Coronary Artery Bypass Graft Surgery in Patients with Ischemic Heart Failure
GOOD MORNING LADIES AND GENTLEMEN
IT IS AN HONOR TO PRESENT THE RESULTS OF THE
SURGICAL TREATMENT FOR ISCHEMIC HEART FAILURE TRIAL
ON BEHALF OF THE STICH INVESTIGATORS
Eric J. Velazquez, MD on behalf of the STICH Investigators April 4, 2011

2. STICH Financial Disclosures
Original Recipient Institution
Principal Investigator
Activity
Duke University Medical Center
Robert H. Jones
Clinical Coordinating Ctr
Kerry L. Lee
Statistical and Data CC
Daniel B. Mark
EQOL Core Laboratory
Univ of Alabama-Birmingham
Gerald M. Pohost
CMR Core Laboratory
Mayo Clinic
Jae K. Oh
ECHO Core Laboratory
University of Pittsburgh
Arthur M. Feldman
NCG Core Laboratory
Northwestern University
Robert O. Bonow
RN Core Laboratory
Washington Hospital Center
Julio A. Panza
DECIPHER Substudy
Baylor University Medical Center
Paul Grayburn
MR TEE Substudy
THE STICH TRIAL WAS FUNDED BY
THE NATIONAL HEART, LUNG AND BLOOD INSTITUTE
THROUGH SEVERAL GRANTS TO THE INVESTIGATIVE TEAM
AND ADDITIONALLY SUPPORTED BY
A GENEROUS CONTRIBUTION FROM ABBOTT LABORATORIES
Funding Sources:
National Heart, Lung and Blood Institute 97.7%
Abbott Laboratories 2.3%

3. 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.
CORONARY ARTERY DISEASE
IS A MAJOR SUBSTRATE FOR
HEART FAILURE AND LEFT VENTRICULAR DYSFUNCTION
THE ROLE OF BYPASS GRAFT SURGERY - CABG –
IN PATIENTS
WITH CORONARY DISEASE AND HEART FAILURE
HAS NOT BEEN CLEARLY ESTABLISHED

4. 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
IN THE 1970s
RANDOMIZED TRIALS OF CABG VERSUS MEDICAL THERAPY
FOR CHRONIC STABLE ANGINA
EXCLUDED PATIENTS
WITH SEVERE LEFT EVNTRICULAR DYSFUNCTION
AND
ONLY 4% WERE SYMPTOMATIC WITH HEART FAILURE
SINCE THE 197Os,
THERE HAVE BEEN MAJOR ADVANCES IN
BOTH CABG AND MEDICAL THERAPY
WHICH RENDER THESE DATA OBSOLETE FOR
CONTEMPORARY CLINICAL DECISION MAKING
RECENT OBSERVATIONS STUDIES SUGGEST A ROLE FOR CABG IN PATIENTS WITH HEART FAILURE AND LEFT VENTRICULR DYSFUNCTION
WHICH IS INCREASINGLY UTILIZED FOR THESE PATIENTS
YET SUBSTANTIAL UNCERTAINTY REMAINS
REGARDING THE INCREMENTAL BENEFIT OVER MEDICAL THERAPY

5. 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.
IN THIS CONTEXT
THE STICH TRIAL WAS DEVELOPED
TO TEST THE FOLLOWING HYPOTHESIS
THAT
IN PATIENTS WITH HEART FAILURE, LEFT VENTRICULAR DYSFUNCTION
AND CORONARY DISEASE AMENABLE TO SURGICAL REVASCULARIZATION
CABG ADDED TO INTENSIVE MEDICAL THERAPY
WOULD DECREASE
ALL CAUSE MORTALITY
WHEN COMPARED TO MEDICAL THERAPY ALONE

6. 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
WE DESIGNED AN UNBLINDED RANDOMIZED TRIAL
WHICH WAS INVESTIGATOR INITIATED AND LED
FUNDED BY THE NHLBI
MANAGED BY THE DUKE CLINICAL RESEARCH INSTITUTE
OVERSEEN BY AN INDEPENDENT DATA AND SAFETY MONITORING COMMITTEE
AND SUPPORTED BY A
BLINDED
CLINICAL EVENTS COMMITTEE
AND CORE LABORATORIES

7. Endpoints Primary Endpoint All-cause mortality
Major Secondary Endpoints
Cardiovascular mortality
Death (all-cause) + cardiovascular hospitalization
OUR RPIMARY ENDPOINT WAS
ALLL CAUSE MORTALITY
IMPORTANT SECONDARY ENDPOINTS
INCLUDED
CARDIOVASCULAR MORTALITY
AND
ALL CAUSE DEATH OR CARDIOVASCULAR HOSITALIZATION

8. Statistical Assumptions and Analyses
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
OUR PRIMARY ANALYSIS PLAN WAS
TO COMPARE THE 2 TREATEMENT ARMS
AS RANDOMIZED
ACCORDING TO THE INTENTION TO TREAT PRINCIPAL
ADDITIONALLY
AS PRE-SPECIFIED IN THE PROTOCOL
COMPARISON OF THE
2 ARMS
WERE PERFORMED
FOR ALL MAJOR ENDPOINTS
WITH ADJUSTMENT FOR
KEY BASELINE VARIABLES
TO ASSESS THE IMPACT OF CROSSOVERS IN FOLLOW-UP,
AS TREATED
AND PER PROTOCOL ANALYSES
WERE ALSO PERFORMED
OUR STATSISTICAL PLAN USED THE FOLLOWING ASSUMPTIONS
MEDICAL THERAPY ALONE
WOULD LEAD TO 25% MORTALITY AT 3 YEARS
CABG WOULD REDUCE MORTALITY BY 25%
THE CROSSOVER RATE
FROM MEDICAL THERAPY TO CABG
WOULD BE LESS THAN 20%
AND
AFTER 400 OR MORE DEATHS
WE WOULD HAVE 90% POWER
TO TEST OUR HYPOTHESIS
Model 3 Covariate adjusted – all variables prospectively specified in STICH protocol or with significant prognostic effect.
Stratum, age, gender, race, HF class at baseline, MI history, previous revascularization, best available EF, number of diseased vessels, chronic renal insufficiency, MR, stroke hx, AF hx

9. 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)
TO BE INCLUDED IN THIS TRIAL
PATIENTS HAD TO HAVE
AN EJECTION FRACTION OF 35% OR LESS
CORONARY DISEASE SUITABLE FOR CABG
AND
TO BE ELIGIBLE FOR MEDICAL THERAPY ALONE
WHICH WE DEFINED
AS THE ABSENCE OF
LEFT MAIN DISEASE
SEVERE DISABLING ANGINA
NOT RESPONDING TO
MEDICAL THERAPY ALONE

10. 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
PATIENTS WERE EXCLUDED IF THEY HAD A
RECENT MYOCARDIAL IFARCTION
WHERE IN CARDIOGENIC SHOCK
IF A PERCUTANEOUS PROCEDURE WAS PLANNED
IF THEH HAD AORTIC VALVE DISEASE
WARRANTING SURGICAL INTERVENTION
OR HAD
A LIFE LIMITING NON-CARDIAC ILLNESS

11. STICH Revascularization Hypothesis
1212
Randomized
CABG
MED only
610
602
THE STICH TRIAL ENROLLED
1212 PATIENTS
AT 99 CLINICAL CENTERS IN 22 COUNTRIES
FROM JULY 2002 TROUGH MAY 2007
602 PATIENTS WERE RANDOMIZED TO MEDICAL THERAPY ALONE
AND
610 PATIENTS WERE REANDOMIZED TO
MEDICAL THERAPY WITH CABG
99 clinical sites in 22 countries
Enrollment: July 2002 – May 2007

12. Selected Baseline Characteristics
Variable
MED (N=602)
CABG (N=610)
Age, median (IQR), yrs
59 (53, 67) 
60 (54, 68) 
Female, % 12
Diabetes, % 40 39
Prior Myocardial infarction, % 78 76
Prior Heart Failure within 3 months, % 95 94
Prior PCI or CABG, % 15 16
LVEF (%) — median 28 27
Multi-vessel disease (>50%), %
91 
Proximal LAD stenosis (>75%), % 69 67
BASELINE CHARACTERIZED WERE WELL MATCHED
BETWEEN THE 2 ARMS
THE MEDIAN AGE WAS 59
405 HAD DIABETES
OVER 75% HAD HAD A PRIOR MYOCARDIAL INFARCTION
AND
OVER 90% HAD HAD SYMPTOMATIC HEART FAILURE IN THE LAST 3 MONTHS
THE MEDIAN EF WAS 28%
OVER 90% HAD MULTIVESSEL DISEASE
WITH MORE THAN 70% HAVING
SUBSTANTIAL STENOSIS OF THE
PROXIMAL LEFT ANTERIOR DESCENDIG ARTERY

13. Medical Therapy MED (N=602) CABG (N=610) Medication, % Baseline
MED (N=602)
CABG (N=610)
Medication, %
Baseline
Latest Follow-up
Latest Follow-up
Aspirin 85 84 80
Aspirin or warfarin 91 93 92
ACE inhibitor or ARB 88 89
Beta-blocker 90 83
Statin 87 79
K+ sparing diuretic 46 53 54
ICD 2 19 15
MEDICATION USE WAS
EXCELLENT
AND WELL MATCHED
BETWEEN THE 2 ARMS
AT BASELINE
AND REMAINED SO
THROUGH FOLLOW-UP

14. CABG Conduct Variable CABG (N=610) CABG received — no (%) 555 (91)
Time to CABG, days — Median (IQR)
10 (5, 16)
Performed electively, % 95
Arterial conduits ≥ 1, % 91
Venous conduits ≥ 1, % 86
Total grafts ≥ 2, % 88
Length of stay, days — Median (IQR)
9 (7, 13)
91% OF THE PATIENTS RANDOMIZED TO CABG
UNDERWENT CABG
AT A MEDIAN TIME OF 10 DAYS
FROM RANDOMIZATION
AT CABG
OVER 905 RECEIVED
AN ARTERIAL CONDUIT
AND
88% RECEIVED
2 OR MORE BYPASS GRAFTS

15. 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
FROM AUGUST THROUGH NOVEMBER 2010
A FOLLOW-UP STATUS WAS ACHIEVED IN
99.6% OF THE PATIENTS RANDOMIZED
THE 5 PATIENTS NOT EVALUABLE DURING THAT PERIOD
HAD A MEDIAN FOLLOW-UP
OF 40 MONTHS
THE MEDIAN OVERALL DURATION
OF FOLLOWUP IN OUR TRIAL WAS
56 MONTHS
AND NOW IT IS MY PRIVILEGE TO PRESENT OUR FINDINGS

16. All-Cause Mortality — As Randomized
HR 0.86 (0.72, 1.04)
P = 0.123
0.46
0.41
AMONG THE 602 PATIENTS
RANDOMIZED TO MEDICAL THERAPY ALONE
THE OVERALL ALL CAUSE MORTALITY RATE WAS 46%
AMONG THE 610 PATIENTS RANDOMIZED TO MEDICAL THERAPY WITH CABG
THE OVERALL MORTALITY RATE WAS 41%
THIS ABSOLUTE RISK REDUCTION OF 5%
CORRESPONDED TO A HAZARD RATION OF 0.86 WITH CABG
THIS WAS NOT STATISTICALLY SIGNIFICANT

17. 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
AFTER ADJUSTING FOR PRE-SPECIFIED BASELINE VARIABLES
THE HAZARD RATIO FOR CABG WAS 0.82
WHICH CORRESPONDED TO A
P VALUE OF 0.039
Model 3 Covariate adjusted – all variables prospectively specified in STICH protocol or with significant prognostic effect.
Stratum, age, gender, race, HF class at baseline, MI history, previous revascularization, best available EF, number of diseased vessels, chronic renal insufficiency, MR, stroke hx, AF hx

18. 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
AMONG THE 602 PATIENTS
RANDOMIZED TO MEDICAL THERAPY ALONE
THE OVERALL CARDIOVASCULAR MORTALITY RATE WAS 39%
AMONG THE 610 PATIENTS RANDOMIZED TO MEDICAL THERAPY WITH CABG
THE OVERALL MORTALITY RATE WAS 32%
THIS ABSOLUTE RISK REDUCTION OF 7%
CORRESPONDED TO A HAZARD RATIO WITH CABG OF 0.8 1
AND A P VALUE OF 0.050

19. Death or Cardiovascular Hospitalization — As Randomized
0.68
0.58
HR 0.74 (0.64, 0.85)
P < 0.001
Adjusted HR 0.70 (0.61, 0.81) P < 0.001
FOR THE ENDPOINT OF ALL CAUSE DEATH OR CARDIOVASCULAR HOSPITALIZATION
THE OVERALL EVENT RATE WAS
68% WITH MEDICAL THERAPY ALONE
AND
58% WITH CABG
THIS ABSOLUTE EVENT REDUCTION OF 10% IN FAVOR OF CABG
WAS STATISTICALLY SIGNIFICANT WITH AND WITHOUT ADJUSTMENT

20. Time-varying Hazard Ratios — As Randomized
AS ANTICIPATED
WHEN ANALYZING EVENT RATES
DURING DIFFERENT TIME PERIODS
THERE WAS AN EARLY HAZARD WITH CABG
RELATIVE TO MEDICAL THERAPY ALONE
IN THE FIRST 30 DAYS AFTER RANDOMIZATION
AFTER 2 YEARS, THIS HAD REVERSED

21. STICH Revascularization Hypothesis Treatment As Received
1212
Randomized
MED only
610
602
Randomized
CABG
17% 9%
537 55 65
555
DURING FOLLOW-UP
65 OF THE 602
PATIENTS RANDOMIZED TO MEDICAL THERAPY
RECEIVED CABG
AND
55 OF THE 610 PATIENTS
RANDOMIZED TO CABG
REMAINED ON MEDICAL THERAPY ALONE
TO EXPLORE THE IMPACT
OF THE DIFFERENTIAL RATE OF CROSSOVERS
BETWEEN THE 2 ARMS
WE PERFORMED AN AS TREATED ANALYSIS OF
THE 592 PATIENT WHO RECEIVED MEDICAL THERAPY ONLY
AND THE 620 PATIENTS WHO RECEIVED CABG
EITHER AS RANDOMIZED OR DUE TO A CROSSOVER FROM MEDICAL THERAPY
ADDITIONALLY
WE ALSO PERFORMED A PER PROTOCOL ANALYSIS COMPARING ONLY THE 537 PATIENTS RANDOMIZED TO MEDICAL THERAPY WHO REMAINED ON MEDICAL THERAPY AND THE
555 PATIENTS RANDOMIZED TO CABG WHO RECEIVED CABG BY PROTOCOL
Received
MED only
Received
CABG
As treated MED (592) vs CABG (620)

22. All-Cause Mortality — As Treated
HR 0.70 (0.58 – 0.84)
P < 0.001
0.49
0.38
AS TREATED
THE HAZARD RATIO FOR ALL CAUSE MORTALITY
WITH CABG WAS 0.70
AND CORRESPONDED TO
A P VALUE OF LESS THAN 0.001

23. STICH Revascularization Hypothesis Treatment Per Protocol
1212
Received
MED only
CABG
555
537
Randomized
MED only
610
602
Randomized
CABG
17% 9% 55 65
WE ALSO PERFORMED
A PER PROTOCOL ANALYSIS
COMPARING ONLY THE 537 PATIENTS RANDOMIZED TO MEDICAL THERAPY
WHO REMAINED ON MEDICAL THERAPY
AND
THE
555 PATIENTS RANDOMIZED TO CABG WHO RECEIVED CABG BY PROTOCOL ONLY
Per protocol: MED (537) vs CABG (555)

24. All-Cause Mortality — Per Protocol
HR 0.76 (0.62, 0.92)
P = 0.005
0.48
0.37
WHEN COMPARING THE
537 PATIENTS WHO REMAINED ON MEDICAL THERAPY ONLY AS PER PROTOCOL
AND THE
555 PATIENTS WHO RECEIVED CABG PER PROTOCOL
THE HAZARD RATIO FOR ALL CAUSE MORTALITY
WITH CABG WAS 0.76
AND CORRESPONDED TO
A P VALUE OF LESS THAN 0.001

25. 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 non- fatal outcomes could have been influenced by the knowledge of the treatment received

26. 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%
TO SUMMARIZE
WE COMPARED CABG
WITH CONTERMPORARY EVIDENCE-BASED MEDICAL THERAPY ALONE
AMONG HIGH RISK PATIENTS WITH
CORONARY DISEASE, LEFT VENTRIULAR DYSFUNCTION AND HEART FAILURE
DESPITE EXCELLENT MEDICAL ADHERENCE AND OPERATIVE RESULTS
STICH-LIKE PATIENTS REMAIN
AT SUBSTANTIAL RISK
WITH A 5 YEAR MORTALITY RATE OF 40%

27. Conclusions
In patients randomized to STICH, there was no statistically significant difference in all- cause 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
IN OUR PRIMARY INTETNION TO TREAT ANALYSIS
OF ALL CAUSE MORTALITY
WE DID NOT FIND A STATISTICALLY SIGNIFICANT DIFFERENCE
BETWEEN MEDICAL THERAPY ALONE
AND CABG
CABG
SIGNIFICANTLY REDUCED CARDIOVASCULAR MORTALITY AND MORBIDITY
COMPARED TO MEDICAL THERAPY ALONE
WHEN RANDOMIZED TO CABG
PATIENTS ARE EXPOSED TO AN EARLY RISK

28. 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.
WE BELIEVE OUR RESULTS HAVE SEVERAL IMPORTANT CLINICAL IMPLICATIONS
THE PRESENCE AND EXTENT OF CORONARY DISEASE SHOUD BE ASESSED AND MEDICAL THERAPY OPTIMIZED FOR ALL PATIENTS WITH HEART FAILURE WITH LEFT VENTRICULAR DYSFUNCTION
DECISION MAKING FOR CABG IS COMPLEX
SHOULD BE INDIVIDUALIZED
AND TAKE INTO ACCOUNT
THE SHORT-TERM RISK FOR LONG-TERM BENEFIT
WE WILL NEED TO WAIT THE RESULTS OF THE STICH EXTENSION STUDY
WHICH WILL TEST THE DURABILITY OF THE RESULTS PRESENTED TODAY
AFTER 10 YEARS OF FOLLOW-UP

29. 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
WE WOULD LIKE TO THANK
ALL STICH INVESTIGATORS AND COORDINATORS WORLDWIDE
AND
MOST IMPRTANLT RECOGNIZE THOSE PATIENTS
WITHOUT WHOSE PARTICIPATION IN CLINICAL RESEARCH
THE STICH TRIAL WOULD NOT HAVE BEEN COMPLETED

30. Full report available online at NEJM.org
FOE A FULL REPORT OF THESE RESULTS
PLEASE VISIT
THE NEW ENGLAND JOURNAL OF MEDICINE
ONLINE
THANK YOU