LANDMARK TRIALS IN STABLE CAD

Dr.O.Adikesava NaiduM.D.,D.M.,FACC,FESC

Assos.Professor in Cardiology,

Osmania Medical College/OGH,

Hyderabad.

Introduction

• Stable Ischemic Heart Disease is most commonly (?) caused by

atheromatous plaque that gradually narrows one or more of the

epicardial coronary arteries.

• IHD - Leading cause of death worldwide.*

• Burden of CAD shifting to lower socioeconomic groups.

• Increase in CV risk factors.

• WHO – estimated rise in CAD deaths in 2020 – 11.1 million (7.6

million in 2005).*

AHA: International Cardiovascular Disease Statistics.Dallas,AHA 2009

Plaque

centric

hypothesis

Removing stenoses does not

consistently treat IHD

• COURAGE trial (N=2,287) evaluation of PCI on top of medical

therapy (optimal ?), 30% of patients were still symptomatic with

angina 1 year after PCI.

• Incidence of angina was not significantly different.

• No difference in composite end point.

Boden et al, Optimal medical therapy with or without PCI for stable coronary disease.

N Eng J Med 2007;356:1053-16.

We need to look beyond..

Marzilli M, Bairey Merz CN et al,

Obstructive coronary atherosclerosis and ischemic heart disease:an elusive link,

J Am Coll Cardiol 60;951,2012.

What is HEART score?

• Is there any benefit of achieving lower BP (target <120 mm

hg) compared to usually recommended (target <140 mm Hg)?

• Does normalisation of BP in CVD patients has any benefit

of CV outcomes?

ACCORD BP study

• High risk Type 2 Diabetics

• Intensive therapy (SBP<120mm Hg) vs Standard therapy( SBP

<140mm Hg).

• 4733 pts

• The primary composite outcome was nonfatal MI, nonfatal stroke, or

death from CV causes.

• The mean follow-up was 4.7 years.

Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus

The ACCORD Study Group

N Engl J Med 2010; 362:1575-1585.

In patients with type 2 diabetes at high risk for cardiovascular

events, targeting a SBP of <120 mm Hg, as compared with <

140 mm Hg, did not reduce the rate of a composite outcome of

fatal and nonfatal major cardiovascular events.

• Are ACEI beneficial in patients with normal LV function but

at risk of CV events?

• Role of ACEI beyond improving LV dysfunction?

(pleiotropic effects)

HOPE trial

The Heart Outcomes Prevention Evaluation

Study

• Vascular disease or diabetes plus one other CV risk factor, not

known to have low LVEF or HF(<40%).

• 9297 pts.

• >55 years of age.

• Ramipril (10 mg/day) vs placebo

Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients.

The Heart Outcomes Prevention Evaluation Study Investigators

N Engl J Med 2000; 342:145-153

End points/Results

• Primary - composite of MI, stroke or death from CV causes.

P<0.001

Conclusion : Ramipril significantly reduces the rates of

death,myocardial infarction,and stroke in a broad range of

high –risk patients who are not known to have a low ejection

fraction or heart failure.

HOPE - Summary of Results

• Patients randomized to ramipril had risk

reductions of:

– MI, stroke, CV death -22%

– CV death -25%

– MI -20%

– Stroke -31%

– Revascularization procedures* -16%

– New onset of diabetes -32%*Revascularization procedures included PTCA, CABG or peripheral angioplasty

N Engl J Med, January 20, 2000

• Does addition of ACEI over conventional therapy in

patients with stable CAD have a favorable outcome?

• Does the effects of ACEI apply to low risk CAD patients?

EUROPA trialEUropean trial on Reduction Of cardiac events with

Perindopril in stable coronary Artery disease

• Low risk patients with stable CAD

• 12,218 pts

• Perinodpril (8mg/day)

• Follow up (mean 3.4 yrs)

Primary – Composite of CV mortality, nonfatal MI, and cardiac

arrest.

Secondary – Composite of total death, nonfatal MI, and cardiac

arrest; heart failure; revascularization (PCI/CABG); and stroke.

Lancet 2003 Sep 6;362(9386):782-8

EUROPA Trial

CV death/non-fatal MI/

cardiac arrest p=0.0003

8.0%

9.9%

0%

5%

10%

15%

Perindopril Placebo

3.5%

4.1%

0%

1%

2%

3%

4%

5%

Perindopril Placebo

European Society of Cardiology 2003

CV Mortalityp=0.107

Among patients with stable CAD, treatment with the ACE-I

perindopril was associated with a reduction in the primary

endpoint of cardiovascular mortality, non-fatal MI, and cardiac

arrest compared with placebo.

PEACE trialPrevention of Events with Angiotensin Converting

Enzyme Inhibition

• 8290 pts,Double blind, placebo controlled

• Trandolapril (4mg/d) vs placebo .

• Primary end point – death from CV causes,MI or coronary

revascularization.

• Mean age of patients – 648 yrs,

• LVEF 58 9 %

N Engl J Med 2004; 351:2058-2068

Results

• 72% underwent revascularization previously.

• 70% received lipid lowering drugs.

• Primary end point was seen in 21.9% (trandolapril) vs 22.5% (placebo)

(p= 0.43) .

PREVENT studyProspective Randomized Evaluation of the Vascular Effects

of Norvasc Trial

• Amlodipine (Norvasc) vs placebo (5 mg -10 mg) {RCT}

• Angiographically documented CAD – slowing of progression of

lesions with baseline of 30% stenosis.

• Reduction in atherosclerosis in carotids by IMT.

• Rates of clinical events

• 825 pts,36 months

Circulation.2000; 102: 1503-1510

Conclusions— Amlodipine has no demonstrable effect on angiographic

progression of coronary atherosclerosis or the risk of major

cardiovascular events but is associated with fewer hospitalizations for

unstable angina and revascularization.

CCBs

Trial Regimen Protocol Results

CAPARES trial Amlodipine 10

mg/day

2 weeks before

angioplasty

Less incidence of

angina (p = 0.04)

EST,48hr ambulatory

ECG at 2 weeks and

20 weeks post PTCA

Exercise induced

ischemia reduced by

40%(p=0.009)

Ischemia of Holter

ECG reduced by

28%(p=0.009)

ACTION study Long acting nifedipine No effect on major or

CV events

(n=7665 pts) 52% hypertensives Reduced need for

PTCA /CABG

Can J Cardiol. 2000 Jul;16 Suppl D:8D-11D

Expert Rev Cardiovasc Ther . 2008 Sep;6(8):1055-62

CARISA trialCombination Assessment of Ranolazine In

Stable Angina trial

• Effect of ranolazine over the OPTIMAL MEDICAL therapy.

• Symptomatic stable CAD pts.

• OMT –Atenolol ,amlodipine or diltiazem

• 750mg or 1000 mg Ranolazine vs placebo

Twice-daily doses of ranolazine increased exercise capacity and provided

additional antianginal relief to symptomatic patients with severe chronic

angina taking standard doses of atenolol, amlodipine, or diltiazem,

without evident adverse, long-term survival consequences over 1 to 2

years of therapy.

JAMA 2004 Jan 21;291(3):309-16.

What is the mechanism of action of trimetazidine?

Trimetazidine

• Metabolic agent

• Inhibits the enzyme 3-ketoacyl coenzyme A thiolase,the terminal

enzyme in b oxidation pathway.

• Enhances glucose metabolism.

• Energy production with less oxygen consumption.

• Improves endothelial function by increasing NO production.

Drugs. 1999 Jul;58(1):143-57

TRIMPOL II

• Efficacy and tolerability of trimetazidine in combination with

metoprolol.

• Randomized,double blind,parallel group,placebo controlled

study.

• 426pts

• Placebo or trimetazidine 20 mg tid over metoprolol 50 mg bd.

• TMT at baseline,4 weeks,8 weeks,12 weeks.

After 12 weeks, there were significantly greater improvements in the

Metoprolol+trimetazidine group in

Time to 1 mm ST segment depression,

Total workload,

Time to onset of angina,

maximum ST segment depression,

mean weekly number of angina attacks,

mean weekly nitrate consumption, and

grade of anginal pain.

There was no evidence of any development of tolerance to trimetazidine.

The tolerability of trimetazidine was excellent.

European Heart Journal (2001) 22, 2267–2274

STUDY DRUGS No. ASSEESSMENT RESULTS

TACT CT+TMZ (60 mg) vs

CT +placebo

117 pts Exercise capacity TED – increased

by 89 seconds,

TI increased by

99 sec

TA +100 sec

A/W decreased

by 51%.

VASCO

angina

study

70 mg/d TMZ,140mg/d

TMZ in CSA

645 pts Exercise capacity TED increased

by 6%,TI

increased by

9.6%

Chazov et al ,Am J Ther 2005;12(1):35-42.

Vitale C et al, Int J Cardiol.2103;168(2)1078-81.

TED –TOTAL EXERCISE DURATION

TI – TIME TO 1mm ST DEPRESSION

TA -TIME TO ANGINA

A/W – ANGINA PER WEEK

TACT

• Chronic stable angina with LV systolic failure on OMT

• 10,917 pts

• 5mg bid – 7.5 mg bid

• Ivabradine did not improve the CV death rate or hospital admissions

rates for acute MI or acute heart failure.

Sub group analysis –

• Among patients with RHR > 70 /min – reduction in hospital

admissions for non fatal MI, unstable angina and coronary

revascularization. Cardiology, 2008;110(4):271-82

• Elevated HR an established marker of CV risk.

• Chronic CAD without HF and HR >70/min.

• CCS II angina

• Ivabradine 10 mg bid vs placebo

• THR 55-60/min

N Engl J Med 2014; 371:1091-109

• No difference in primary end point or CV deaths.

• Increase in the incidence of the primary end point among patients with

activity-limiting angina ( p=0.02 ).

• The incidence of bradycardia was higher with ivabradine than with

placebo (18.0% vs. 2.3%, p<0.001).

CONCLUSIONS :

Among patients who had stable coronary artery disease

without clinical heart failure, the addition of Ivabradine to

standard background therapy to reduce the heart rate did not

improve outcomes.

TRIAL drug Follow up Results

SAPAT trial

(2035 pts)

1 st trial in CSA

Aspirin (75 mg /d) 50 months Primary outcome – 34%

reduction (p =0.003)

Secondary events

reduction by 22-33%

Non significant adverse

events

CAPRIE trial Clopidogrel (75

mg/d)vs Aspirin

(325 mg/d)

36 months 8.7% relative decrease in

the risk of vascular

death,ischemic stroke,or

MI among patients with

established

atherosclerotic vascular

disease.(p=0.043)

Lancet1992 Dec 12;340(8833):1421-5.

Lancet 1996 Nov 16;348(9038):1329-39.

ANTI PLATELETS

CAPRIE: Superior Efficacy of Clopidogrel

versus ASA

*MI, ischemic stroke or vascular death†Intent-to-treat analysis (n=19,185)

CAPRIE Steering Committee. Lancet 1996; 348: 1329–1339.

0

4

8

12

16

0 3 6 9 12 15 18 21 24 27 30 33 36

Months of follow-up

Cu

mu

lati

ve

even

t ra

te*

(%

) ASA

Clopidogrel

8.7%† RRR (p=0.043)

20

Patients with recent ischemic stroke, recent MI or symptomatic PAD

CAPRIE: Clopidogrel Reduced the Rate of

Rehospitalization

Bhatt DL et al. Am Heart J 2000; 140: 6773.

*Rehospitalization for ischemia (angina pectoris, TIA, limb ischemia) or bleeding (gastrointestinal,

intracranial or other)†On-treatment analysis (n=19,099)

Patients with recent ischemic stroke, recent MI or symptomatic PAD

5 10 15 20 25 30 35

9.1%† RRR

(p=0.018)

Months of follow-up

Cu

mu

lati

ve

even

t ra

te*

(%

)

0

5

10

15

20

ASA

Clopidogrel

CHARISMA trial

• Dual antiplatelet therapy.

• 15603 pts,28 months

• Clinically evident CVD or having risk factors

• Clopidogrel 75mg/d + aspirin 75-162 mg/d vs palcebo + aspirin

75 mg/d

Am Heart J 2004 Aug;148(2):263-8

Overall Population: Primary Efficacy Outcome (MI,

Stroke, or CV Death)†

† First Occurrence of MI (fatal or non-fatal), stroke (fatal or non-fatal), or cardiovascular death

*All patients received ASA 75-162 mg/day§The number of patients followed beyond 30 months decreases rapidly tozero and there are only 21 primary efficacy events that occurred beyond this time (13 clopidogrel and 8 placebo)

Bhatt DL, Fox KA, Hacke W, et al. NEJM 2006.

Cu

mu

lati

ve

even

t ra

te (

%)

0

2

4

6

8

Months since randomization

0 6 12 18 24 30

Placebo + ASA*

7.3%

Clopidogrel + ASA*

6.8%

RRR: 7.1% [95% CI: -4.5%, 17.5%]

p=0.22

• In this trial, there was a suggestion of benefit with clopidogrel

treatment in patients with symptomatic atherothrombosis and a

suggestion of harm in patients with multiple risk factors.

• Overall, clopidogrel plus aspirin was not significantly more

effective than aspirin alone in reducing the rate of myocardial

infarction, stroke, or death from cardiovascular causes

Women and CAD

HERS

The Heart and

Estrogen/Progesti

n Replacement

Study

Estrogen + progestin in

post menopausal women

CAD pts No morbidity or

mortality benefit

Increased risk of

DVT,PE

Postive – reduction

in

LDL(10%),increase

d HDL by (11%)

HERS II Follow up of patients

enrolled in HERS

6.8yrs

2321 post

menopaus

al women

Increased risk of

VTE

JAMA. 1998;280(7):605-613

JAMA 2002 Jul 3;288(1):58-66.

WHICompared with the placebo, estrogen plus progestin resulted

in:

• Increased risk of MI,stroke

• Increased risk of DVT,PE

• Increased risk of breast cancer

• Reduced risk of colorectal cancer

• Fewer fractures

• No protection against mild cognitive impairment and increased risk

of dementia (study included only women 65 yrs)

https://www.nhlbi.nih.gov/whi/index.html

Compared with the placebo, estrogen alone resulted in:

• No difference in risk for MI

• Increased risk of stroke

• Increased risk of DVT,PE

• Uncertain effect for breast cancer

• No difference in risk for colorectal cancer

• Reduced risk of fracture

4S trial

Scandinavian Simvastatin Survival Study

• Benefits of Cholesterol lowering in 4,444 pts with CAD.

• TC : 212-309 mg/dl

• Prior MI and angina pectoris.

• Simvastatin 20mg/day – 40 mg/day

• Goal of cholesterol - 116-200 mg/dl

• Primary – Total mortality

• Secondary – Major adversed coronary events

• Tertiary – Effect on PTCA/CABG procedures,event free survival.

Lancet,Vol 344, 8934, p1383–1389, 1994

Primary Endpoint: Overall

Survival

80

82

84

86

88

90

92

94

96

98

100

0 1 2 3 4 5 6

Simvastatin

Placebo

Years since randomization

% S

urv

ivin

g

30%

risk reductionp = 0.0003

The Lancet, Vol 344, November 19, 1994

• What is the trial which showed high dose statin is beneficial

in management of CSA patients and is safe with less

complications related to drug?

AVERT trialAtorvastatin Versus Revascularization Treatment

• Aggressive lipid therapy (atorvastatin 80 mg/d) or PTCA followed by

usual care(lipid lowering drugs also included).

• 18 month study

• 341 pts.

• LDL>115mg/dl, TG>500mg/dl, CCS II, Bruce protocol > 4 min,

stenosis >50% in coronaries.

• Primary – cardiac death,cardiac arrest,need of PTCA/CABG

• Secondary – time to ischemia event,worsening angina,changes in

lipoproteins.

Mean percentage diameter of coronary stenosis – 80%.

Interesting points:

1.Reduction of ischemic events in atorvastatin group by 36%.

(p=0.048)

2.Long time for occurrence of ischemia > 6 months (p=0.03)

3.Routine use of atorvastatin(80mg/day) – safe – only four

developed complications.

Can J Cardiol. 2000 Jan;16 Suppl A:11A-3A

TNT

Treating to New Targets study

• 10,003 pts

• Atorvastatin 10 mg vs atorvastatin80 mg.

• Target of LDL -100 mg/dl for 10 mg and

75 mg /dl for 80 mg

Am J Cardiol. 2004 Jan 15;93(2):154-8.

No difference in all cause mortality between

high dose and low dose atorvastatin

TNT

MANAGEMENT OF

STABLE CAD

ABCDE of SIHD patient

management

• A –Aspirin, Antianginals

• B – Betablockers, Blood pressure control

• C – Cholesterol management,C igarette cessation

• D – Dietary improvements, Diabetes control.

• E – Education and Exercise.

ESC/EHA Guidelines for stable CAD,2012

PCI vs OMT

COURAGE trialClinical Outcomes Utilizing Revascularization and

Aggressive DruG Evaluation

• PCI + OMT vs OMT

• Severe angiographic disease of one or more vessels(>70%

stenosis),and either classic symptoms or documented ischemia

on provocative testing.

• 2287 pts randomized.

• Follow up 2.5-7 yrs (median 4.6 yrs).

Circulation. 2008; 117: 1283-1291.

What is the motto?

Test

a strategy of routine anatomically driven PCI plus OMT

versus

a strategy of selective,ischemia driven PCI, if needed for

failure of initial OMT.

Results

• Death or MI occurred with similar frequency in both arms

(p=0.62).

• No difference in hospitalization for ACS (p = 0.56) or MI

(p=0.33).

• Less angina at 1 and 3 yrs but not at 5 yrs in PCI pts.

• Increased PCI in patients on OMT.

Conclusion:

As an initial management strategy in patients with SIHD,

PCI did not reduce death,MI or other major CV events when added to

OMT.

Important features of COURAGE

cohort

• Highly symptomatic at baseline.

• Clinical comorbidities.

• High prevalence of objective evidence of myocardial ischemia.

• Extensive angiographic CAD.

Patient cohort

• 42-43% no angina or class I angina

• 30% SVD

• 35% LAD

• EF -61%

• DES was not routinely available.

What went wrong?

• 1.low cardiac mortality in stable angina patients.

• 2.improved endothelial function over long term on OMT.

• 3.collateralization - alleviation of symptoms in patients on OMT.

• 4.Adherence of patients on OMT (80%).

• 5.Benefits of PCI were diluted - disease progression in other vessels

or the failure to provide complete revascularization initially.

• 6.ACS can occur at site other than severe stenosis.

Subgroup analysis

No difference between PCI plus OMT vs OMT in

• CCS class II or III angina

• Diabetes

• Low LV EF

• Multivessel CAD

Break to Anatomically driven PCI…

FAME 2 Trial

• FFR < 0.8 in one or more visually stenotic coronary arteries(>50%

stenosis)

• FFR+ PCI + OMT vs OMT

• 1632 pts (2 yrs)

• Premature termination (Highly significant reduction in composite end

point at 7m).

• 68% RR reduction in PCI vs OMT (12.7% vs 4.3%) (p<0.001)

• Lower rate of urgent revascularization in PCI group.(1.6% vs11.1 %)

( p < 0.001)

N Engl J Med 2012; 367:991-100

How was the positive result?

• No uptitration of Medical therapy in patients who were

symptomatic.

• Patients who were symptomatic were randomized to PCI without

objective evidence of ischemia or biomarker positivity.

• 52% patients underwent early revascularization.

• PATIENTS WERE NOT ON OPTIMAL MEDICAL

THERAPY

FFR strategy

• FFR helps in stenting of lesions which are physiologically

siginificant (FFR <0.80) rather than

anatomically(>50%stenosis),thereby decreasing the new

disease which is as a result of PCI+ stenting.

• What is the latest advanced technology with relation to

FFR?

• What is the Trial evidence?

Instantaneous wave free ratio(iFR)

• Vasodilator free pressure-only measure of the hemodynamic

severity of a coronary stenosis.

• Alternative to FFR

• CLARIFY study.

• VERIFY study.

• RESOLVE study.

• Further studies needed to take on iFR as effective replacement for

FFR.

ISCHEMIA trial

CABG vs Medical Therapy

CABG improves the survival rate among patients with

• High risk stable angina.

• 3V CAD

• Impaired LV function.

• Substantial LMCA stenosis.

• CASS (Coronary Artery Surgery Study)

• ECSS (European Coronary Surgery Study)

• VATS(Veterans Administration Cooperative Study)

Why CABG was superior?

• Studies were done in era of low awareness of benefit of OMT.

• No trials have been done so far in comparison of CABG with OMT

PCI vs CABG

S.No Trial Profile No .of patients

Follow up

Result

1 EAST Mmultivessel CAD 400pts ,8 yrs No benefit of PCI

Left main disease Non significant improved

survival in CABG

2. BARI Multivessel CAD 7 yrs No difference

Diabetics Better survival rate with

CABG (76.4% vs55.7%)

3. ARTS Multivessel CAD 1,200 pts,1 -5 yrs No difference

Diabetics Increased mortality in PCI

4. ARTS 2 DES was used Similar rate of

revascularization

Multivessel CAD

J Am Coll Cardiol. 2001;38(1):143-149

S.No Trial Profile Follow up Result

5 BARI2D trial Type2DM+CAD

PCI or CABG vs OMT

No difference between two

groups.

Revascularization wise

greater freedom of events in

CABG group (p=0.01)

NEJM 2009;360:2503-12

SYNTAX trialSYN ergy between PCI with TAXus and cardiac surgery

• 3VD or LMCA

• Multivessel PTCA vs CABG

CABG PCI P value

Primary End point

Death,stroke,MI,repeat revascularization

12.3% 17.6% 0.002

Secondary end point death,stroke,MI 7.7% 7.6% 0.98

Repeat revascularization 5.9% 13.5% < 0.001

Rate of stroke 2.2% 0.6% 0.003

Circulation: Cardiovascular Interventions.2009; 2: 463-467

N Engl J Med 2009; 360:961-972

Class I indication for evaluation of LMCA or Multivessel

disease(ACC/AHA 2013 PCI guidelines).

• Grading of coronary anatomy on basis of

– lesion location

– Complexity

– Functional impact

• Assess patients at individual level.

• Helps in CABG vs PCI

Low score 0-22

No difference

Intermediate 23-32

No difference

High score >32

CABG was better

STICH trial

• 1212 ICMP with reduced EF.

• 462 deaths over 56 months of follow up.

• CABG did reduce CV deaths (p=0.09).

• Sudden deaths were reduced in CABG (p=0.041).

• Fatal pump failure events (p=0.05).

• Protective effect of CABG occurred after 24 months.

• Post procedure deaths increased in CABG patients.

• Fatal MI were lower.

Conclusion:

Addition of CABG to medical therapy is beneficial

in patients with stable angina and reduced EF(ICMP)

Beneficial effects were seen after 2 years.

Panza et al,JACC 2013

• What is meant by Unprotected Left Main Disease?

• What is Left Main Equivalent?

• In what proportion of patients undergoing angiography,is

Unprotected Left main disease seen?

• 4% cases

Asymptomatic , non flow limiting , angiographically insignificant

disease(< than50%)

Ostial,Ostio proximal

Shaft : Mid, distal or diffuse Left main

Bifurcation lesion

Non functional CABG grafts ( eg: LIMA occlusion makes LAD

unprotected).

Left main equivalent: significant (70 percent or more) stenosis of

proximal left anterior descending (LAD) artery and proximal left

circumflex artery

Left main disease arm (SYNTAX trial)

CABG PCI P value

Primary outcome Same

Stroke 2.7% 0.3% 0.009

Repeat

revascularization

6.5% 11.8% 0.02

N Engl J Med 2009; 360:961-972

FREEDOM trial

• Diabetics with MVD

• PCI+DES vs CABG

• 1900 pts

• 29% were women

• 83% had TVD.

• Primary outcome occurred more frequently in PCI group (p=0.005).

• MI decreased in CABG group(p<0.001)

• Stroke was most common in CABG group.(p=0.03)(5.7 vs 2.4)

N Engl J Med 2012; 367:2375-238

Can we predict risk when stenting the LMS?

TRIAL DESIGN NO. RESULT

PRECOMBAT N = 1454

Premier of

RandomizEd

COMparison of

Bypass Surgery

versus Angioplasty

Using Sirolimus-

Eluting Stent in

Patients with Left

Main Coronary

Artery Disease

Prospective

Open label

Randomized trial

First trial in UPLMD

Sirolimus stent vs

CABG

IVUS has been used. PCI with sirolimus

eluting stent appears a

potential alternative to

CABG with a

noninferior incidence

of 2-year MACCE for

patients with ULMCA

stenosis.

LE MANS 105 pts

Study of unprotected

LEft MAiN Stenting

versus bypass

surgery

Randomized

Open label

Direct stenting in PCI

Bifurcation

technique ,Initial

stent to LAD then

Cullotte or Prov T if

necessary.No crush

stenting

IVUS advised

PCI noninferior to

CABG

N Engl J Med 2011;364:1718-27

LEMANS trials, J Am Coll Cardiol 2008

LeMans survival

Post MI

TRIAL DESIGN NO. RESULTS

SWISS II

Swiss

Interventional

Study on Silent

Ischemia Type

II

PCI effect in patients

with silent ischemia

post MI

201 Pts

PCI vs OMT

Aspirin 100

mg/d

Statin 80 mg/d

PCI better

Less MACE (p=0.001)

Lower rates of ischemia (p=0.03)

LVEF preserved at 1 yr

DANAMI PCI or CABG vs

OMT

503 Pts

Follow up 1.2-

4.5 yrs

PCI vs CABG better

Non significant improvement in

mortality.

Less MI (p=0.03)

Less angina

(p<0.001)

OAT 2166 pts The 4-year cumulative primary event

rate was 17.2% in PCI and 15.6% in

OMT (P=0.20).

Rates of MI (fatal and nonfatal) were

7.0% and 5.3% ; (P=0.13). Rates of

nonfatal reinfarction were 6.9% and

5.0%, P=0.08); There was no

interaction between treatment effect

and any subgroup variable

JAMA, 2007 May 9;297(18):1985-91

Circulation.1997; 96: 748-755

N Engl J Med 2006; 355:2395-240

EECP

EECP

• The Multicenter Study of Enhanced External Counterpulsation

(MUST-EECP):

• 139 pts

• EECP vs OMT

• Exercise duration increased in both groups, (p < 0.3).

• Time to >1-mm ST-segment depression increased significantly from

baseline in active CP compared with inactive CP (p < 0.01).

• More active-CP patients saw a decrease and fewer experienced an

increase in angina episodes as compared with inactive-CP patients (p

< 0.05).

• Nitroglycerin usage decreased in active CP but did not change in the

inactive-CP group. The between-group difference was not significant

(p = 0.7).

EECP reduces angina and extends time to exercise-induced

ischemia in patients with symptomatic CAD.

Treatment was relatively well tolerated and free of limiting

side effects in most patients.

J Am Coll Cardiol. 1999;33(7):1833-1840

Trials in pipeline

EXCEL trial

• Abott cardiovascular systems

• XIENCE PRIME or XIENCE V vs CABG in left main disease.

Inclusion criteria :

• Unprotected left main coronary artery (ULMCA) disease with

angiographic diameter stenosis (DS) ≥70% requiring

revascularization, or

• Main Equivalent Disease

• Silent ischemia, stable angina, unstable angina or recent MI.

http://www.invasivecardiology.com/issue/4148

Angiographic exclusion criteria:

• Left main diameter stenosis <50%

• SYNTAX score ≥33

• Left main reference vessel diameter <2.25 mm or >4.25 mm.

• Results yet to be published.. Dec 2016

Recommendations

Conclusions

• OMT is essential in all patients with stable angina.

• In patients with Diabetes,TVD – CABG >PCI.

• PCI+DES > PCI +BMS with relation to restenosis.

• In left main, PCI+DES = CABG > OMT.

• Asymptomatic Post MI pts. OMT = PCI or CABG.

• CABG – mortality benefit, morbidity benefit, less target

vessel revascularization,increased risk of stroke.

• PCI - improved quality of life, less angina, but increased

revascularization,restenosis,mortality.

• SYNTAX SCORE > 33 – CABG.

The appearance of a disease is swift as an

arrow; its disappearance slow, like a thread.

When a disease relapses there is no cure.

---Chinese proverb