Angioplasty of the culprit lesion has been proven to be of value:1. ST elevation MI compared to thrombolytics

Reduces mortality and strokes (and likely reinfarction)

2. In high risk non-ST elevation ACSReduces new MI and likely deaths and avoids repeated rehospitalization for UA.

In both acute conditions, appropriate and timely PCI is an important advance.

But PCI is commonly used in individuals with stable coronary artery disease (with or without angina)

Is this appropriate or have we gone too far ?

Primary Prevention v Stable Angina v Unstable AnginaDeath / MI after 12 months

Dea

th/ M

I (%

)

Months of follow up

Unstable angina/non Q wave MI (FRISC II)

16

12

8

4

00 2 4 6 8 10 12

Stable angina (SAPAT)

Wallentin L et al. Lancet 2000;356:9–16Juul-Moller S et al. Lancet 1992;340:1421–1425Shepherd J et al. N Engl J Med 1995;333:1301–1307

Primary Prevention (WOSCOPS)

STABLEANGINA

Abrupt interruptionof coronary blood flow

PRIMARYMYOCARDIAL ISCHEMIAACUTE

CORONARYSYNDROME

STABLE PLAQUE

Platelet deposition,thrombosis, spasm

Increased myocardialoxygen demand (oxygen supply doesnot meet the demand )

SECONDARYMYOCARDIAL ISCHEMIA

PLAQUE RUPTURE

High arrhythmogenicpotential

Myocardial Ischemia: Pathophysiology

Stenosis Grade Before AMI

8%8%

0123456789

Aspirin Aspirin-bloq

Aspirin-bloqStatin

Aspirin-bloqStatinACEI

None

6%6%

4,5%4,5%

3%3%2,3%2,3%RRRRRR

25%25%RRRRRR30%30% RRRRRR

25%25%

RRRRRR25%25%

SECONDARY PREVENTION

Eventrate*

(2 years)

Impact of pharmacological treatmentImpact of pharmacological treatment

**CV death, AMI or strokeYusuf S. Lancet 2002;360:2

StatinACEI

-bloq

Aspirin

Summary of CABG surgery vs initial medical management (33% “cross-over”) at 7 years

Mortality RRROverall 33% p<0.001L Main 66% p<0.013VD 33% p<0.0012VD/1VD + prox LAD 20% p<0.051 or 2VD, no prox LAD 0%MI No effectSince these trials were initiated some 2 to 3 decades earlier surgical techniques have improved (IMA, periop complications, better graft survival, ?? off pump)

RITA-2: PTCA vs Medical Therapy in Stable Angina(n=1000)

PTCA Medical OR P

Death/MI 32 (6.3%) 17 (3.3%) 1.91 0.02

CABG 40 (7.2%) 30 (5.8%) 1.24 -

Post-rand PTCA 62 (12.3%) 101 (19.9%) 0.62 0.001

Any PTCA 533 (>100.0%) 101 (19.9%) 5.28 <<0.0001

Total procedures 577 131 4.50 <<0.0001

Lancet 1997

RITA-2: Impact on Grade 2 Angina (Med v PTCA)

RITA-2 Lancet 1997

Quality of Life by Treatment Group over 3 years of Follow-up

Pocock et al. JACC 2000

PCI vs Medical TherapyMeta-analysis of PCI vs medical therapy in 6 RCTs on a total of about 2000 pts

Conclusion: “The procedure should be used only in patients in whom angina cannot be controlled by medical treatment, although CABG is an alternative.” Bucher et al BMJ 2000

Trials of Aggressive Medical Therapy vs PCI

AVERT (Pitt et al): Atorvastatin superior to routine PCI in preventing ischemic events (p<0.04)

Hambrecht et al: Exercise training superior to PCI in preventing ischemic events (6 v 15; p <0.02)

Hambrecht et al. Circ 2004Pitt et al. NEJM 1999

PCI vs medical therapy

• PCI is probably INFERIOR to medical therapy in preventing major clinical events..

• BUT HAVE STENTS/DES MADE A SUBSTANTIAL DIFFERENCE?

POBA vs PCI+stents

OR (95% CI) P

Death or MI 0.90 (0.72-1.11) N.S.CABG 1.01 (0.79-1.31) N.S.

Angio restenosis 0.52* (0.37-0.69) 0.001

Repeat PTCA 0.59* (0.50-0.68) 0.001

Conclusion: Stents have no impact on death/MI-Routine stenting prevents 4 to 5* repeat PCI per 100 stented

Meta-analysis of 29 trials involving 9918 patients

*?overestimate of effect because of lack of blinding. Brophy et al

Drug Eluting Stents vs BM Stents

OR (95% CI) P

Death 1.11 (0.61, 2.06) -

MI 0.92 (0.65, 1.25) -

Angio restenosis 0.18 (0.06-0.40) 0.001

Target vessel revasc 0.26 (0.14-0.45) 0.001

11 trials involving 5103 patients

Babapulle et al Lancet 2004

100

90

80

70

60

50

1 2 3 4 5 60

Surv

ival

(%)

Time (years)

No restenosis (n = 1.570 )Restenosis (n = 1.793 )

93%93%95%95%

p = 0.16

No impact on Prognosis of RestenosisAfter PCI:10yr Emory experience

Weintraub WS et al. Circulation 1993; 87: 831

But is preventing restenosis the most important issue in preventing MI or deaths?

1. If PCI is not done, restenosis is zero!2. Restenosis is a poor predictor of events3. Therefore PCI :

-deals with a very small part of the problem (as most events arise from other segments of a CAD), i.e. anatomically “restricted”(analogous to removing a tumor, but leaving all the metastatic lesions alone)-wrong physiology(creates plaque reupture in a stable lesion)-creates iatrogenic problems: (acute and late occlusions, restenosis)- DES may increase late non-cardiac and cardiac mortality .

PCI(+/-stents) does NOT reduce(and may even increase) mortality / MI

Increased death or MI in 1st g-DES as compared to control:Latest followup of all RCTs

38

16

0

10

20

30

40

50

60

70

80

90

100

SES PES

delta

rate

of d

eath

or Q

-MI

of 1

st g

-DES

vs

BM

S (%

)

%

%

+

+

Late Complications of DES

• Increase in late MI and death?(Camenzid et al ESC 2006)

• Increased non-cardiac deaths (cancers,infections)?(Nordmann et al,ESC 2006)-prolonged delivery of low doses of an antimitotic agent not only to the local vessel wall, but also systemically?

- Is this similar to prolonged chemotherapy or immune suppression?

- Vascular wall may not have re-endothelialized even after several year.

LATE INCREASE IN TOTAL MORTALITY?

Multi-vessel Disease: A meta-analysis of Mortality for PTCA vs CABG

Hoffman et al. JACC 2003

Long Term Outcomes: CABG vs Stenting

New York registry of 37,212 patients with multivessel disease undergoing CABG vs 22,102 patients undergoing stents (1997-2000)

Hannan et al NEJM 2005

Conclusions:PCI in stable CAD

1) Single vessel disease: PCI does not reduce mortality, may increase MI, at a substantial increase in costs.

2) Multivessel disease: CABG is superior to PCI in reducing mortality, angina and repeated revascularization, and is cost effective .

DES increases late MI and deaths ,and costs markedly. Therefore, PCI + DES is far less effective,perhaps even

harmful and more expensive than medical management or CABG.

Rebuttal

Management of Multivessel Disease: Clinical Implications

• Aggressive medical management and risk factor control: Can reduce future events by >75%.

• PCI in stable CAD is a Palliative procedure. • In 1 or 2 VD (without prox LAD), full antianginals preferred,

(with PCI or CABG reserved for refractory symptoms).• In multivessel disease, CABG is superior to PCI.• PCI is inappropriately over-used, leading to

inferior patient management at high costs.

Cost effectiveness of StentsReport of Health Technology Assessment Working

Group of the UK NHS

1. BMS vs CABG: Long term outcomes favour CABG over stents2. DES vs CABG: Even less cost effective.3. DES vs BMS in 1 VD:

Substantially higher costs, very small benefit, so DES is not cost-effective .

Implications to NHS:Current stenting in the UK, use of DES increases costs by up to £25 mill per year (with little clinical benefit)

Impact in North America and Europe is much greater.

Do you believe in fairies? If you believe, clap your hands!

                                                                                                                          

What is the Basis of the Cardiology Community’s Preoccupation with PCI?1. Incorrect expectations on an unproven theory (lumenology)2. Lack of realization that relief of angina is modest and short term.3. What you see (stenosis) is the problem. What you do not see

(extent of disease, vulnerability and content of plaque) is not relevant. Similar to dealing with a tumor, but not the metastases!

4. A regressive spiral of chasing iatrogenic complications ( thrombotic occlusions and restenosis are man made!)

5. Lack of appreciation that alternatives are cheaper, less risky and more effective than PCI .

6. Truly informed consent is rare, especially with same sitting PCI

What is the Basis of the Cardiology Community’s Preoccupation with PCI?5. Emotional appeal: “You have a critical blockage of your artery to the heart

and I can fix it with a balloon and stent….without cracking open your chest”. Implications: (All untrue)

-you are in serious trouble and we can avoid it by PCI-Better than medical treatment,and similar to CABG

-Fewer complications. Not stated:

-Lack of evidence and Need for repeat procedures6. Influences of device, stent and drug manufacturers (of course, we

physicians would never succumb to such pressures!)7. Personal income and prestige (TARZAN syndrome: sense of heroism!)

BeforeBefore

After 8 plastic surgeriesAfter 3 TAXUS

COSMETICEFFECT

A humble plea to societies and colleagues who care about patient’s health

• The inappropriate over-use of PCI and related devices in stable CAD is epidemic.• A huge drain and diversion of resources• Diverts attention from :

a) Proven alternativesb) Patients and physicians are misinformed c) Trainees are mistaughtd) Distorted financial incentives and influencese) Direction of research is wrong (chasing the wrong questions)

CONVENE AN INDEPENDENT A BALANCED REVIEW COMMITTEE (NON-INTERV CARDIOLOGISTS, INTERVENTIONISTS, SURGEONS, PAYORS, PATIENT ADVOCATES),HEALTH ECONOMISTS WITH NO INVOLVEMENT OF INDUSTRY CHAIRED BY AN EXPERT IN EVALUATING EVIDENCE

“Overuse of PCI and stents in stable coronary disease is an expensive step backwards.”

“The great tragedy of Science: the slaying of a beautiful hypothesis by an ugly fact “

~ Thomas Huxley

Conclusions

Declaration of Interests

I have consulted with many pharmaceutical companies, received research grants, honoraria , free meals,pens and travel expenses. I have not been courted by the manufacturers of devices, balloons, or stents chiefly because it would do them no good. I confess I have never performed an angioplasty or CABG surgery (my patients and my colleagues would not want me to), but referred lots of patients to my expert colleagues…..and I have a preference for evidence over hunches and impressions.