the case for pci as the preferred therapy in most patients ... · mv-adjusted 0.85 (0.56–1.30)...
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Columbia University Medical CenterColumbia University Medical CenterThe Cardiovascular Research FoundationThe Cardiovascular Research Foundation
The Case for PCI as the The Case for PCI as the Preferred Therapy in Most Preferred Therapy in Most
Patients with Chronic Patients with Chronic Stable AnginaStable Angina
Ajay J. Ajay J. KirtaneKirtane, MD, MD
Conflict of Interest Disclosure
• Ajay J. KirtanePast honorarium from Boston Scientific Corporation (modest)Consultant/Speaker: Medtronic Vascular, Abbott Vascular (modest), St. Jude Medical (modest)
The Term “Stable Angina” Can Be Confusing
• “Stable Angina” is a Term Describing Symptoms, not a Diagnosis!!!
“Stable Angina” encompasses a range of patient /disease characteristics (including patients with NO angina!)*
• Not only are the symptoms of “stable angina” diverse, but so is the prognosis
• The risk of the specific population being studied is of paramount importance
*2002 ACC/AHA Guidelines
Two Goals of Therapy inPatients with Stable Angina
1. Improve Symptoms and Quality of Life
Measured by “soft endpoints”(i.e. angina/QOL scales)
2. Improve PrognosisMeasured by “hard endpoints”(i.e. death, MI)
Therapies for “Stable Angina”• Medical Therapy (ALL Patients)
Antiplatelet Therapy (Aspirin, ADP-antagonists)Disease Modification (Statins, anti-DM, anti-HTN)Lifestyle Modification (Diet, Smoking Cessation, Exercise)Anti-Anginals (Beta-blockers*, Nitrates, Calcium-Channel Blockers)
• Revascularization (Selected Patients?)PCICABG
Med Rx vs. PCI: Angina/QOL at ≥1 Year
Trial QOL Angina ETTACMEACME PCI betterPCI better PCI betterPCI better PCI betterPCI better
ACME 2ACME 2 ↔↔ ↔↔ ↔↔MASSMASS PCI betterPCI better
ACIPACIP PCI betterPCI better PCI betterPCI better
RITARITA 22 PCI betterPCI better PCI betterPCI better
AVERTAVERT PCI betterPCI better PCI betterPCI better PCI betterPCI better
MASS IIMASS II PCI betterPCI better PCI betterPCI better
TIMETIME PCI betterPCI better PCI betterPCI better PCI betterPCI better
9 randomized trials9 randomized trials
COURAGECOURAGE PCI betterPCI better PCI betterPCI better
Effect of Optimal Medical Therapy
But The Baseline Population is Critical!43% Class 0-1 (+32% PCI) ≈ 72% Angina Free
But The Baseline Population is Critical!But The Baseline Population is Critical!43% Class 043% Class 0--11 (+32% PCI) (+32% PCI) ≈≈ 72% Angina Free72% Angina Free
Freedom From Angina in COURAGE
PCI + OMT OMT p
Baseline 12% 13% NS1 Year 66% 58% 0.001
3 Years 72% 67% 0.025 Years 74% 72% NS
Model of Angina Distribution in COURAGE
Log-normal Distribution
0
0.05
0.1
0.15
0.2
0.25
0 5 10 15 20 25
Prob
. den
sity
00.10.20.30.40.50.60.70.80.91
Dis
tribu
tion
func
tion
Prob. density Distribution function
Average One per Week
32% Crossover
Mean 6 episodes/weekMedian 3 episodes/week
Distribution must be skewed!
Hiratska et al for the Get With The Guidelines Steering Committee, Circulation. 2007;116:I-207–I-212
Secondary Prevention Performance Measures are Implemented More
Frequently After PCI in CAD Patients
Perform. Measure CABG PCI None pACE Inhibitor 57.3 74.0 66.3 <0.0001Aspirin 97.1 99.4 94.5 <0.0001Beta Blocker 90.8 91.0 88.2 <0.0001Smoking Advice 82.4 84.8 73.9 <0.0001Lipid Drug 77.4 89.2 72.3 <0.0001Defect-Free 100% Compliance 65.1 71.5 62.1 <0.0001
Med Rx vs. PCI: Angina/QOL at ≥1 Year
Trial QOL Angina ETTACMEACME PCI betterPCI better PCI betterPCI better PCI betterPCI better
ACME 2ACME 2 ↔↔ ↔↔ ↔↔MASSMASS PCI betterPCI better
ACIPACIP PCI betterPCI better PCI betterPCI better
RITARITA 22 PCI betterPCI better PCI betterPCI better
AVERTAVERT PCI betterPCI better PCI betterPCI better PCI betterPCI better
MASS IIMASS II PCI betterPCI better PCI betterPCI better
TIMETIME PCI betterPCI better PCI betterPCI better PCI betterPCI better
COURAGECOURAGE PCI betterPCI better PCI betterPCI better
9 randomized trials9 randomized trials
MetaMeta--analysis of 11 randomized trials; N = 2,950analysis of 11 randomized trials; N = 2,950
DeathDeathCardiac death or MICardiac death or MI
Nonfatal MINonfatal MICABGCABG
PCIPCI
KatritsisKatritsis DG et al. DG et al. Circulation. Circulation. 2005;111:29062005;111:2906--1212..
0 1 2
PP0.680.68
0.280.28
0.120.12
0.820.82
0.340.34
Risk ratio (95% Cl)
Favors PCI
Favors Medical Management
Pre-COURAGE: Stable CADPTCA/BMS vs. Medical Therapy
Number at RiskMedical Therapy 1138 1019 962 834 638 409 192 120PCI 1149 1015 954 833 637 418 200 134
Years0 1 2 3 4 5 6
0.0
0.5
0.6
0.7
0.8
0.9
1.0
PCI + OMT
OMT
7
Hazard ratio: 1.13Hazard ratio: 1.1395% CI (0.8995% CI (0.89--1.43)1.43)
P = 0.33P = 0.33
Freedom from MI (any biomarker elevation) (median FU 4.6 yrs)
BodenBoden WE et al. NEJM 2007;356:1503WE et al. NEJM 2007;356:1503--1616
Free
dom
from
MI (
%)
MIat 4.6 yrs
12.3%13.2%
Spontaneous MI108 PCI + OMT
119 OMT
Periprocedural MI35 PCI + OMT
9 OMT
COURAGE: A Very Low Risk GroupAnnual CV Death Rates in “Stable” CAD
StegSteg JAMA;297;1197; JAMA;297;1197; StettlerStettler Lancet 2007;370:937;Lancet 2007;370:937;HjemdahlHjemdahl Heart 206;92:177Heart 206;92:177
1.8
1.1
2.7
0.4
0
1
2
3
Beach n=68, 236Network Meta n=18,023APSIS n=809COURAGE n=2,287
CV Death
Columbia University Medical CenterColumbia University Medical CenterThe Cardiovascular Research FoundationThe Cardiovascular Research Foundation
There is a Wide-Range of Morbidity/Mortality among “Stable Angina” Patients
Hachamovitch et al, Circulation 2003;107:2900-07
% Total Ischemic Myocardium
0% 1- 5% 5-10% 11-20% >20%
Car
diac
Dea
th R
ate
(%)
(1.9
yr F
U)
N=7110 N=1331 N=718 N=545 N=252
N=9,956 pts
5.4% cardiac mortality in 1.9 years -
Is this “stable” angina?
MPS % Ischemic Myocardium(95% CI) Pre-Rx & 6-18 Months
0
40
5
10
15
20
25
35
30
Pre-Rx 6-18m
8.2% 5.5%(4.7%-6.3%)
PCI + OMT (n=159)PCI + OMT (n=159) OMT (n=155)OMT (n=155)
0
40
5
10
15
20
25
35
30
Pre-Rx 6-18m
(6.9%-9.4%)
8.6% 8.1%
Mean = -2.7%(95% CI = -3.8% to -1.7%)
Mean = -2.7%(95% CI = -3.8% to -1.7%)
Mean = -0.5%(95% CI = -1.6% to 0.6%)
Mean = -0.5%(95% CI = -1.6% to 0.6%)
p<0.0001p<0.0001
Shaw, et al, AHA 2007 and Circulation 2008
13.4%
24.7%
0%
10%
20%
30%
40%
Dea
th o
r MI R
ate
(%)
Rates of Death or MI byIschemia Reduction
p=0.037p=0.037
Ischemia Reduction ≥5%(n=82)
RR=0.47 (95% CI=0.23-0.95)
No Ischemia Reduction(n=232)
Shaw, et al, AHA 2007 and Circulation 2008
0.0%
15.6%
22.3%
39.3%
0%
10%
20%
30%
40%
Dea
th o
r MI R
ate
(%)
Rates of Death or MI by ResidualIschemia on 6-18m MPS
p=0.002p=0.002
0%(n=23)
p=0.023p=0.023
p=0.063p=0.063
1%-4.9%(n=141)
5%-9.9%(n=88)
>10%(n=62)
Shaw, et al, AHA 2007 and Circulation 2008
6.7%
4.8%
2.9%
1.0%
0%
2%
4%
6%
8%
10%
Gradient of risk according to ischemic burden1.9 yrs of Follow-up with Medical Therapy
% Total Ischemic Myocardium1- 5% 5-10% 11-20% >20%
Car
diac
Dea
th R
ate
1331 718 545 252
Hachamovitch et al Circulation 2003; 107:2900-2907
6.7%
3.7%3.3%
1.0%
2.9%
4.8%
1.8% 2.0%
0%
2%
4%
6%
8%
10%Medical Rx Revasc
Mitigatated Gradient with Revasuclarization
% Total Ischemic Myocardium1- 5% 5-10% 11-20% >20%
Car
diac
Dea
th R
ate
1331 56 718 109 545 243 252 267
P <.0001
Hachamovitch et al Circulation 2003; 107:2900-2907
Hemodynamics Predict Prognosis: DEFER Study 5 year follow-up
15.7%
5.6%
0.0%
5.0%
10.0%
15.0%
20.0%
Pijls et al. JACC 49, 2007;2105–11
FFR ≥ 0.75 FFR < 0.75n=181 n=144
Cardiac Death or MI
P=0.003
Five-year Survival with Balloon Angioplasty or Stents vs. Coronary Artery Bypass Grafting in
Patients with Multivessel Disease
-0.15 -0.08 0.00Greater Survival
with CABG
Bravata et al, Ann Intern Med. 2007;147.
Study, Year (Reference) Surviving Patients/All Patients,n/n
Risk Difference (95% CI)
PCI CABGBARI, 1996 (64) 790/915 816/914EAST, 2000 (80) 153/174 161/177GABI, 2005 (88)* 164/177 157/165RITA, 1998 (110) 483/510 474/501French Monocentric Study, 1997 (126) 66/76 68/76
Balloon overall 1656/1852 1676/1833ARTS, 2005 (23) 542/590 538/584AWESOME, 2001 (28) 30/38 19/26ERACIII, 2005 (86) 209/225 199/225MASS II, 2006 (103) 177/205 171/203
BMS overall 958/1058 927/1038MVD overall 2614/2910 2603/2871
Greater Survival with PCI
0.08 0.15
NY State CABG vs. DES (Adjusted)NY State CABG vs. DES (Adjusted)
Hannan et al, N Engl J Med 2008;358:331-41
PCI vs. CABG for PCI vs. CABG for MultivesselMultivessel DiseaseDiseaseAMC Experience (Korea)AMC Experience (Korea)
Mortality EstimateMortality Estimate Hazard Ratio (95% CI)Hazard Ratio (95% CI) pp
CrudeCrude 0.65 (0.470.65 (0.47––0.90)0.90) 0.010.01
MVMV--AdjustedAdjusted 0.85 (0.560.85 (0.56––1.30)1.30) 0.450.45
PropProp--AdjustedAdjusted 0.95 (0.720.95 (0.72––1.53)1.53) 0.680.68
PropProp--StratifiedStratified 0.90 (0.590.90 (0.59––1.37)1.37) 0.630.63
Park et al, Circulation 2008;117:2079-2086
Registry series of all-cause mortality to 3 yrs in3042 patients treated with PCI or CABG
ARTS IIARTS II –– MACCE up to 3 YearsMACCE up to 3 YearsEv
ent f
ree
Surv
ival
(%) 100
9590858075706560
Time (Months)
0 6 12 18 24 30 36
83.8%80.6%
66.0%
P (log rank) = 0.22P (log rank) = 0.22 between ARTS II and ARTS I-CABG
P (log rank) <0.001P (log rank) <0.001 between ARTS II and ARTS I-PCI
ARTS IIARTS IIARTS I CABGARTS I CABGARTS I PCIARTS I PCI
From P. SerruysEurointervention 2007; 3: 450-459
TakeTake--Home PointsHome Points•• The Measured Benefit of any Therapy The Measured Benefit of any Therapy
over Another Depends on:over Another Depends on:Relative effectiveness of the therapyRelative effectiveness of the therapyBaseline Risk (event rate)Baseline Risk (event rate)Measured goal of therapy (outcome)Measured goal of therapy (outcome)
•• To measure risk in Stable CAD, we need to To measure risk in Stable CAD, we need to look at severity of symptoms, extent of look at severity of symptoms, extent of ischemia, and absolute event ratesischemia, and absolute event rates
NonNon--novel findingnovel finding: In symptomatic or : In symptomatic or ““higherhigher--risk ptsrisk pts””, , revascrevasc will be beneficialwill be beneficial
Summary: Who Should NOT Get PCI?Summary: Who Should NOT Get PCI?
•• I favor Medical Therapy in:I favor Medical Therapy in:Asymptomatic or mildly symptomatic Asymptomatic or mildly symptomatic patients with no or very little ischemiapatients with no or very little ischemiaPatients in whom Patients in whom revascrevasc. is too risky. is too risky
•• I favor CABG in:I favor CABG in:Patients/disease subsets who are poor Patients/disease subsets who are poor candidates for PCI, but we need more candidates for PCI, but we need more trial results to better define this trial results to better define this population (we will soon have these)population (we will soon have these)
2006-2007 PCI Under Attack
2007-2008 Critical Reappraisal / Emerging Data
2008-???? Let’s RESUME Moving Forward!
Where Do We Go From Here?