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?