The “Truth and Consequences” of Objective Ischemia: The COURAGE Trial Nuclear Substudy Dean J. Kereiakes, M.D. Medical Director, The Christ Hospital Heart.

The “Truth and Consequences” of Objective Ischemia: The COURAGE Trial Nuclear Substudy

Dean J. Kereiakes, M.D.Medical Director, The Christ Hospital Heart and Vascular Center and the Lindner Research CenterChairman,Executive Committee, The Ohio Heart and Vascular Center, Cincinnati, OhioProfessor of Medicine, Ohio State University

Objectives

• Identify pivotal observation(s) from the COURAGE trial nuclear substudy

• Is this observation(s) novel?

• Is the obsevation realistic and applicable to clinical practice?

• What are the limitations & caveats regarding COURAGE observations?

• Summary and Conclusions

Nuclear Substudy (n=314 / 2,287)

Hypothesis: Reduction in ischemia will be greater for patients Randomized to PCI+OMT than for those randomized to OMT

Serial rest/stress myocardial perfusion SPECT (MPS)To compare patient management strategy for ischemia reduction

DocumentedPre-Rx Ischemia

PCI + OMT OMT (n=159) (n=155)

Repeat MPS* Repeat MPS* at 6-18m at 6-18 m

*Timing chosen to occur beyondwindow of in-stent restenosisand delayed to allow effects of medical Rx to be observed

•Pre-Rx = off meds

•Post-Rx = on meds

Source: Shaw et al. J Nucl Cardiol 2006;13:685

MPS Ischemia Based on Total Perfusion Defect (TPD)

• TPD: Quantitative measure of defect extent and severity• % Ischemic myocardium = (Stress TPD-Rest TPD)• < 5%: Minimal (“no ischemia”)• 5.0%-9.9%: Mild 10%: Moderate to severe

•Significant reduction in ischemia

5% reduction in ischemic myocardium*

Source: Simoka et al. J Nucl Cardiol 2005;12:66 *Threshold exceeds test repeatability

TPD

Defect Extent

Lower NILimit

Defect Severity

Pre-Treatment Clinical Characteristics and MPS Results

PCI + OMT

N=159

OMT

N=155

P value

Angina CCS* Class I-II 74% 73% 0.99

Angiographic 2-3 vessel CAD 73% 77% 0.38

Rest gated LVEF 57%11% 58%9% 0.97

% Ischemic myocardium 8.2% 8.6% 0.63

(95% CI) (7.2-9.3%) (7.5-9.8%)

Moderate to Severe Ischemia** 34% 33% 0.81

*CCS=Canadian Cardiovascular Society ** 10% ischemic myocardium

Compared to main trial, substudy patients more often CCS* class I-II angina (p=0.013)& less multivessel CAD (p=0.05); with similar % of MPS ischemia (p=0.55)

33.3

19.8

0

10

20

30

40

50

PCI + OMT (n=159) OMT (n=155)

Isch

emia

Red

uctio

n

5%

Primary Endpoint: % with Ischemia Reduction 5% Myocardium (n=314)

P=0.004

31.4

17.8

0

10

20

30

40

50

PCI + OMT (n=53) OMT (n=29)

% w

ith L

ow R

isk*

MPS

Ischemia Normalization* on Follow-Up MPSIn Patients with Significant Ischemia

Resolution

P=0.007

*1% ischemic myocardium

13.4

24.7

0

10

20

30

40

50

Ischemia Reduction n=82

No Ischemia Reductionn=232

Dea

th o

r MI r

ate

(%)

Rates of Death or MI by Ischemia Reduction

P=0.037

RR=0.47 (95% CI=0.23-0.95)

5%*

*primary endpoint

16.2

32.4

0

10

20

30

40

50

Ischemia Reduction n=68

No Ischemia Reductionn=37

Dea

th o

r MI r

ate

(%)

Rates of Death or MI by Ischemia Reduction in Subset of 105 Patients with Moderate to

Severe Pre-Rx Ischemia*

P=0.001

5%

*50% reduction

0.0

15.622.3

39.3

0

10

20

30

40

50

0% (n=23)

1 - 4.9%(n=141)

5 -9.9%(n=88)

10%(n=62)

Dea

th o

r MI r

ate

(%)

Rates of Death or MI by Residual Ischemia on 6-18m MPS

P=0.002

P=0.023

P=0.063

Conclusions

• PCI added to OMT was more effective in reducing ischemia and improving angina than OMT alone, particularly in patients with moderate to severe pre-RX ischemia

• Is this Observation Novel?

0.3

0.8

2.3

2.9

0.5

2.72.9

4.2

0

1

2

3

4

5

Myocardial Infarction

Cardiac Death

Hachamovitch, Diamond et al. Circ 1998;97:535

Cardiac Death or Myocardial Infarction Rate/Year Stratified by SPECT Quantitative Ischemia

Eve

nt

Rat

e %

* Statistically significant increase as function of scan result** Increased rate of MI vs cardiac death within scan stratum

**

*

*

Normal Mildly Normal Moderately Abnormal Severely Abnormal

N = 2946 884 455 898

0.7 1.0

2.9

4.8

6.76.3

1.8

3.73.3

2.0

0

2

4

6

8

10

7110 16 1331 56 718 109 545 243 252 267

Medical RX Revasc

Hachamovitch et al. Circ 2003;107:2900

Cardiac Death Rate Stratified by Spect Quantification of Ischemia and Treatment Modality†

Car

dia

c D

eath

Rat

e (%

)

0% 1-5% 5-10% 11-20% >20%*p < 0.0001 % Total Myocardium Ischemic†10,627 Consecutive patients followed 1.9 + 0.6 years.

*

§

Hachamovitch et al. Circ 2003;107:2900

Mortality Hazard by Treatment Modality and % Ischemic Myocardium

log

Haz

ard

Rat

io (

Mo

rtal

ity)

0

1

2

3

4

5

6

0 12.5% 25% 32.5% 50%

*p<0.001 % of Total Myocardium Ischemic

Interaction: p=0.030

Medical Rx *

Revasc *

Relationship Between Baseline Findings and Treatment Strategies with Adverse Outcomes* to 1 Year: ACIP Study**

Adapted from Pepine et al. JACC 1997;29:1483

O.R. (95% CI) P

Ischemia Driven 0.80 (0.39 – 1.61) 0.41

Medial Therapy

Revascularization 0.56 (0.26 – 1.2) 0.05

Strategy

AECG Ischemia† 1.06 (1.01 – 1.12) 0.002

0.25 0.5 1.0 1.5 1.75

† 48 hours monitor qualifying visit

*Death, non-fatal MI, hospital admission for ischemic event, **558 pts. Objective ischemia

Ambulatory ECG and SPECT Perfusion Imaging: Lack of Concordance (ACIP Ancillary Study*)

Adapted from Mahmarian et al. JACC 1997;29:764-9

AECG

SPECT

+

-

+ -

50% Concordance ( 3% perfusion defect)52% Concordance (+ any ischemic defect)

45 / 48 33 / 34

20 / 17 8 / 7

0

4

8

12

16

ACIP Study Two-Year Follow-Upp

erce

nt

0 4 8 12 16 20 24

Death or MI

Months of Follow-up

Davies et al. Circ 1997;95:2037

12.1% Angina Guided Med Rx

8.8% Ischemia Guided Med Rx

4.7% Revascularization *

*P<0.01 vs. angina guided med Rx

Cardiovascular Death or Myocardial Infarction Stratified by Self-Reported Angina and/or Inducible Ischemia*:

The Heart and Soul Study

0.5 1 2 3 4 5 6 7 8 9

Adjusted HR† (95% CI) p

No angina or ischemia 1 (Reference)

Angina alone 1.4 (0.7, 2.9) 0.31

Ischemia alone 2.2 (1.4, 3.5) 0.005

Angina & Ischemia 3.2 (1.4, 7.2) 0.006

Adapted from Gehi, Schiller, Whooley et al. Arch Int Med 2008;168:1423

*stress echo (937 pts. Stable CHD followed 3.9 yrs.)† Adjusted for age, sex, race, Hx MI, Hx CHF, HgA1c, CrCl, LVEF, SBP, DBP, CRP

• Is the COURAGE Trial observation Realistic and Applicable to Practice?

COURAGE : DemographicsCOURAGE : Demographics

50 Hospitals50 Hospitals

2,287 pts* 2,287 pts* enrolled between enrolled between

6/99-1/046/99-1/04

1 pt per hospital 1 pt per hospital per monthper month

19 US Non-VA Hospitals19 US Non-VA Hospitals387 pts 387 pts (0.5 pts/mo/hosp)(0.5 pts/mo/hosp)*(17% of total)*(17% of total)

15 VA Hospitals15 VA Hospitals968 pts 968 pts (1.6 pts/mo/hosp)(1.6 pts/mo/hosp)(42% of total)(42% of total)

16 Canadian Hospitals16 Canadian Hospitals932 pts 932 pts (1.5 pts/mo/hosp)(1.5 pts/mo/hosp)(41% of total)(41% of total)

Boden WE et al. NEJM 2007;356:1503-16Boden WE et al. NEJM 2007;356:1503-16

* 15% women,14% non-caucasian

Does COURAGE Represent U.S. PCI Practice ?Does COURAGE Represent U.S. PCI Practice ?

962,732(98.5%)

* 2006* 2006 Boden WE et al. NEJM 2007;356:1503-16 ; US data on file, Boston Scientific Boden WE et al. NEJM 2007;356:1503-16 ; US data on file, Boston Scientific

0

200

400

600

800

1000

1200

1400

1600

1800

2000 US VA US non VA

0

200,000

400,000

600,000

800,000

1,000,000

1,200,000

14,268(1.5%)

Hospitals with PCI * Total PCI Volume*

52(3.5%)

1,422(96.5%)

Co

mp

lete

Co

mp

lete

rev

asc

ula

riza

tio

nre

vas

cu

lari

zati

onP

eri-

PC

IP

eri-

PC

IM

IsM

IsCOURAGE : Inadequate and Incomplete PCICOURAGE : Inadequate and Incomplete PCI

1149 patients total1149 patients total

46 (4%) procedure not attempted46 (4%) procedure not attempted

27 (2%) no lesions crossed27 (2%) no lesions crossed

1077 pts had PCI attempted / 958 (89%) success1077 pts had PCI attempted / 958 (89%) success

[really 958/1149 (83.4%)or 958/1122(87%) success]*[really 958/1149 (83.4%)or 958/1122(87%) success]*

1577/1688(1730)* lesions had PCI success (93%)1577/1688(1730)* lesions had PCI success (93%)

Few PCI pts received GPIIb/IIIa inhibitors, bivalirudin Few PCI pts received GPIIb/IIIa inhibitors, bivalirudin

or adequate clopidogrel pre-loading or adequate clopidogrel pre-loading

787 pts (69%) had 2 or 3 vessel ds.787 pts (69%) had 2 or 3 vessel ds.416 pts (36%) received ≥2 stents416 pts (36%) received ≥2 stents

At least 371 of 787 pts (47%) with multivessel At least 371 of 787 pts (47%) with multivessel disease had incomplete revascularization disease had incomplete revascularization

14% PTCA14% PTCAonlyonly

86% stents86% stents97% BMS97% BMS3% DES3% DES

*Really <89-*Really <89-91%*(add 1.6 91%*(add 1.6 lesn x27 pts) lesn x27 pts)

PC

I su

cces

sP

CI s

ucc

ess

*SITE

COURAGE : Variable PCI Outcomes by LocationCOURAGE : Variable PCI Outcomes by LocationOriginal Trial Hypothesis: 22% reduction D/MI with PCIOriginal Trial Hypothesis: 22% reduction D/MI with PCI

Dea

th/M

I (%

) at

4.6

yea

rsD

eath

/MI (

%)

at 4

.6 y

ears

29%↓29%↓27%↑27%↑

P≈0.02

COURAGE: Mortality by Healthcare System and Randomized Treatment Strategy

12.1

7.9

4.7

8.67.7

6.0

0

2

4

6

8

10

12

14

USVA USNVA Canadian

OMT PCI + OMT

Adapted from Chaitman et al. JACC 2008;51:A222 (abstract)

% Mortality

P =0.07

COURAGE Issues :? Geographic Selection Bias COURAGE Issues :? Geographic Selection Bias D

eath

/MI

(%)

at 4

.6 y

ears

Dea

th/M

I (%

) at

4.6

yea

rs

All USVA

USnon-VA

Canada

N=2287 N=932 N=968 N=387

Original Projection:Original Projection: 3-year death/MI for 3-year death/MI for OMTOMT = 21% = 21%

~ 0.4% /Yr Cardiac Mortality in COURAGE~ 0.4% /Yr Cardiac Mortality in COURAGE NEJM 2007;356:1503 AHJ 2006;151:1173 NEJM 2007;356:1503 AHJ 2006;151:1173

Very low risk pts!Very low risk pts!Hard to improve uponHard to improve upon

ProbablyProbably~10% at~10% at3 years3 years

Imputed* Effect of Drug-Eluting Stents in the COURAGE Trial: Death / MI

0.00 0.50 1.00 1.50 2.00 2.50

RR (95% CI)

BMS+OMT vs. OMT

(COURAGE)

1.05 (0.87,1.27)

DES+OMT vs. BMS+OMT

(historical meta-analysis)

1.30 (0.91,1.86)

1.03 (0.84,1.26)

DES vs. OMT

(indirect comparison)

1.36 (0.91, 2.04)

1.08 (0.82, 1.43)

*Annals Int Med 2006Meta-analysis Diamond, Kaul Viewpoint JACC 2007;50:1604-1609

BMS SES (Cypher) PES (Taxus)

Favors

PCI

Favors

OMT

0

4

8

12

16

20

24

0 1 2 3 4 5

BMS (Exp) n = 295PES n = 287

Clinical Events Following BMS or DES*+

0

4

8

12

16

20

24

0 1 2 3 4

BMS (EXP+Bx)

PES

SES

Boston Scientific data on file

TARGET LESION REVASCULARIZATION CLINICALLY DRIVEN TLR (Taxus IV Non-Angio Cohort)

SES vs. BMS: HR 0.30 (0.24-0.37; p<0.0001) PES vs. BMS: HR 0.42 (0.33-0.53; p<0.0001)SES vs. PES: HR 0.70 (0.56-0.84; p=0.0021)

BMS 4763 820/4746 53/2795 22/1871 10/1543 PES 6328 448/6280 98/3950 15/1999 6/832SES 6621 356/6580 68/3801 16/2153 14/999

*Stettler et al. Lancet 2007;370:937n=18,023 patients / 38 trials

% %

PES vs. BMS: HR 0.39 (0.23-0.67; p=0.0005)

BMS 295 37/254 5/249 3/239 1/229 2/218 PES 287 8/272 4/271 3/258 2/246 3/235

+

p=0.0005)

Clinical Events Following BMS or DES*

0

2

4

6

8

10

0 1 2 3 4

BMS

PES

SES

ALL DEATH DEATH OR MYOCARDIAL INFARCTION Cumulative Incidence in % Cumulative Incidence in %

SES vs. BMS: HR 1.00 (0.82-1.25; p=0.89) HR 0.92 (0.77-1.08; p=0.32)PES vs. BMS: HR 1.03 (0.84-1.22; p=0.75) HR 1.00 (0.84-1.23; p=0.97)SES vs. PES: HR 0.96 (0.83-1.24; p=0.80) HR 0.92 (0.79-1.08; p=0.27)

BMS 4921 109/4904 48/3340 31/2264 44/1875 4921 301/4904 62/3208 45/2161 46/1780PES 6331 138/6283 78/4263 32/2187 15/869 6331 376/6283 115/4087 43/2082 22/833SES 6771 139/6730 72/4041 38/2340 24/10810 6771 356/6730 86/3888 44/2241 28/1032

0

2

4

6

8

10

12

14

0 1 2 3 4

BMS

PES

SES

*Stettler et al. Lancet 2007;370:937n=18,023 patients/38 trials

Mortality (DES vs. BMS) from 29 Trials / RegistriesPatient Year Weighted Regression*

0

2

4

6

8

10

12

14

0 2 4 6 8 10 12 14

% Death BMS

% D

eath

DE

S

STENT

TSEARCH

BASKET

DEScover

Steinberg et al.

REAL

ONASSIS

Pache et al.

PRISON II

DIABETES

SCANDSTENT

TYPHOON

SES Smart

Western Denmark

SCAAR

MISSION

Ortolani

Cypher meta-analysis

Taxus SR meta -analysis

Ontario PCI Registry

WAKE Forest

ACUITY

PASSION

RESEARCH

SESAMI

NY State

ASAN

GHOST

MIDAS

1

3

2

4

5

9

13

17

21

25

29

6

10

14

18

22

26

28

27

24

23

20

19

16

15

12

11

7

8

1

32

4

5

9 13

17

21

25

29

6

10

14

18

22

2628

27

24

23 20

19

16

15

12

117

8

Slope = 1.0

Slope = 0.79

Slope = 0.85[95% CI]

Slope = 0.73[95% CI]

DES Death = 0.79 BMS Death95% CI Slope = 0.79 ± 0.06

R2 = 0.96

DES Death = 0.79 BMS Death95% CI Slope = 0.79 ± 0.06

R2 = 0.96

Size of circle adjusted for number of patients

21% Decrease

5.9

11.512.9

5.6

7.8

11.911.0

7.9

4.25.2

8.6

4.85.5

9.4

5.76.4

0

2

4

6

8

10

12

14

16

18

20 BMS DES

DES vs. BMS Registries: All Cause Mortality

ASAN GHOST MIDAS NY STATE ONTARIO MASS-DAC STENT Western Denmark

%4,

061

3,18

0

871

483

5,39

95,

719

7,83

4

6,38

4

3,75

1

3,75

1

1,35

9

5,99

6

8,84

7

3,54

8

p<0.001 p=0.052 p<0.0001 p<0.05 p<0.001 p<0.001 p<0.001 p=0.004

Follow-up: 3 year 3 year 2 year 2 year 3 year 2 year 2 year 2 year

5,44

15,

441

DJK

Late (3 Year) Results of the SCANDSTENT Randomized Trial*E

ven

ts, %

5.62.5 3.7 4.9

8

12.3

1.9 1.3

9.6

33.8 34.437.6

0

5

10

15

20

25

30

35

40SESBMS

Kelbaek et al. JACC 2008;51:2011

Death Cardiac Myocardial TLR TVR MACE death infarction

p<0.001 p<0.001 p<0.001

* CTO, ostial, bifurcation, angulated

p=0.14 p=0.69 p=0.04

DES Outcomes (2 Years) in the Elderly: Medicare Case-Control Comparison*

% P

ati

ents

10.7 9.2

17.2

29.8

13.511.2

19.1

34.4

0

10

20

30

40

50DES BMS

Adapted from Groeneveld et al. JACC 2008;51:2017

Death Myocardial Coronary Combined Infarction Revascularization Endpoints

p<0.001 p<0.001 p<0.001 p<0.001

*n=76,525 DES Rx vs. contemporary (April-Dec 2003) controls

Outcomes Following Coronary Stenting in Medicare Beneficiaries*

0.00

0.10

0.20

0.30

1 90 180 365 730 1 90 180 365 730

Malenka et al. JAMA 2008;299:2868

Cum

ulat

ive

Haz

ard

0.00

0.02

0.04

0.06

0.08

0.10

0.12

# at risk BMS 38917 35610 33155 30437 26822 38917 38001 37362 36332 34275 DES 28086 25660 24386 22737 19943 28086 27473 27021 26301 24311

Repeat Revascularization Death/STEMI

BMS era DES era

*BMS 38,917 10/02 - 3/03 DES 28,086 09/03 - 12/03

DES Versus BMS and All-Cause Mortality: CCF Experience

1

1.0

0.9

0.8

0.7

0.6

1.0

0.9

0.8

0.7

0.60.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

Years after Procedure

10.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0

Years after ProcedureNo. At RiskDrug Eluting Stent: 6053 5467 4771 3939 3145 2295 1552 791 170Bare-Metal Stent: 1983 1538 1241 1082 990 905 815 723 515

*p<0.001

No. At RiskDrug Eluting Stent: 1801 1654 1466 1251 1037 791 536 261 57Bare-Metal Stent: 1801 1390 1117 969 884 809 733 653 471

Non-Propensity Matched*Event Free

Propensity MatchedEvent Free

Shishenbor et al. JACC 2008 52:1041

Drug-Eluting Stent HR (95% CI) Bare-Metal Stent 0.62( 0.53 - 0.73) Confidence Interval

Drug-Eluting Stent HR (95%CI) Bare-Metal Stent 0.54(0.45-0.66) Confidence Interval

An

gin

a fr

ee (

%)

An

gin

a fr

ee (

%)

CCS Class 0 / 1P=NS

COURAGE : Freedom from Angina with OMTCOURAGE : Freedom from Angina with OMT

40%P<0.001

<10% crossovers*

prespecified!

P=NS

*due to severe / progressive angina ; remain OMT by ITT

Multivariate Predictors of Crossover to PCI

Hypercholesterolemia 1.4 (1.0 - 2.0)

3 VD 1.6 (1.1-2.3)

SAQ angina frequency score

0.86 (0.81-0.91)

Adapted from Spertus et al. JACC 2008;51:A264 (abstract)

0.5 1.0 1.5 2.0 2.5

OR (95% CI)

COURAGE : “COURAGE” OMT not RealisticCOURAGE : “COURAGE” OMT not Realistic

Follow-upFollow-up AspirinAspirin StatinsStatins Beta Beta blockersblockers

1 years1 years 95%95% 95%95% 89%89%

3 years3 years 95%95% 92%92% 86%86%

5 years5 years 94%94% 93%93% 86%86%

LDL < 85 mg per deciliter in ~70% of ptsSBP <130 mmHg in ~65% of ptsDBP <85 mmHg in ~ 94% of pts

HgBA1C <7.0% in ~45% of diabetic pts

Compliance

Treatment to Targets

Medication ComplianceMedication ComplianceCRUSADECRUSADE Registry (1-Year) Registry (1-Year)

Mehta HR et al. Circulation 2005;112:II-793.

vs. 95% in COURAGE

vs. 95%

vs. 89% vs. >90%

vs. >90%

82

66

86

69

55

70

0

10

20

30

40

50

60

70

80

90

100

Aspirin B-Blocker Statin/Lipid Lowering

Previous PCI (n=12,759)Previous Medical Rx (n=13,784)

% P

atie

nts

Adapted from Steinberg, et al. Am J Cardiol 2007;99:1212

Compliance with Guideline Recommended Therapies in Patients with Established Atherosclerosis:

The REACH International Registry

0.500.550.600.650.700.750.800.850.900.951.00

Years Years

Ho et al. Am Heart J 2008;155:772

Medical Compliance Effects Survival in CAD S

urv

iva

l (a

dju

ste

d)

Su

rviv

al (

ad

jus

ted

) 0.500.550.600.650.700.750.800.850.900.951.00

0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8

STATIN BETA-BLOCKERS

Adherent Non-Adherent

Optimal (<140/90 )* Blood Pressure Control in Optimal (<140/90 )* Blood Pressure Control in Clinical PracticeClinical Practice

1J HTN 2006;24:51, 2J HTN 2004;22:2387, 3HTN 2007;49:69 * < 130(65%) / 85(94%) COURAGE

Silvia Study2

(n=2775)

Three City Study1

(n=9090)

NHANES 2003 – 20043

(n=1614)

31%37% 33%%

Pat

ien

ts%

Pat

ien

ts

0

10

20

30

40

50

60

Baseline 1 3 6 12 24 36

PCI + OMTOMT

Months

Weintraub et al. N Engl J Med 2008;359:677

Freedom from Angina ( SAQ ) Stratified by Treatment

P=0.35

P<0.001

P<0.001 P<0.001 P=0.005

P=0.010 P=0.30

n = 21 23 42 33 53 42 56 47 57 50 59 53 59 56

Ang

ina-

free

(%)

Angina Stability and Frequency by SAQ over Time Stratified by Treatment Strategy

0 6 12 24 36 0 6 12 24 36

Months from Baseline Months from Baseline

Weintraub et al. N Engl J Med 2008;359:677

Me

an

Sc

ore

Angina Stability Angina Frequency

Me

an

Sc

ore

100

90

80

70

60

50

0

100

90

80

70

60

50

0

** * *

* * * **

PCI + OMTOMT

*p<0.01

Quality of Life by SAQ Over Time Stratified by Treatment Strategy

0 6 12 24 36

Months from Baseline

Weintraub et al. N Engl J Med 2008;359:677

Me

an

Sc

ore

100

90

80

70

60

50

0

*

* * **

PCI + OMTOMT

*p<0.01

COURAGE Objective Ischemia : Conclusions

• Ischemia (SPECT,AECG,SECHO) is qualitatively and quantitatively correlated with adverse clinical outcomes (CVD,MI)

• Revascularization (PCI) is more effective in reducing ischemia than medical therapy (OMT)

• COURAGE PCI was inadequate (83-87% per-patient ; <89-91% per-lesion success rate) and incomplete (47% MVD) with suboptimal technology (14% POBA, 3% DES)

COURAGE Objective Ischemia : Conclusions

• COURAGE OMT was unrealistic (>90% compliance through 5 years) in part due to free nurse case management and free medications

• Contemporary “real world practice management” (more complete revascularization with DES, less optimal medical compliance) would likely enhance the relative magnitude and durability of demonstrated PCI benefit (angina relief, improved QOL, ischemia reduction)