the “truth and consequences” of objective ischemia: the courage trial nuclear substudy dean j....
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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)