Hyeon-Cheol Gwon · 2013. 7. 23. · Merck Regional Cardiology Symposium 2011 ... CHF = congestive heart failure) ACC/AHA Guideline 2007 for Chronic Angina. Merck Regional Cardiology

Hyeon-Cheol Gwon

Cardiac and Vascular Center, Samsung Medical CenterSunkyunkwan University School Medicine

Samsung Medical Center

Cardiac & Vascular Center

Merck Regional Cardiology Symposium 2011



Treatment Options for CAD

Medical therapy

Revascularization

◦ Percutaneous coronary intervention (PCI)

◦ Coronary artery bypass surgery (CABG)

Experimental therapy

◦ Electric spinal cord stimulation

◦ Angiogenesis

(CAD = coronary artery disease)




Medical Therapy




Clinical Syndromes of CAD

Stable angina

Silent ischemia

Unstable angina

Vasospastic angina

Acute myocardial infarction

Ischemic cardiomyopathy

Syndrome X

Sudden cardiac death

The treatment should be individualized particularly according to

these clinical syndromes.




Medical Management of Stable Angina

Short acting sublingual or buccal nitrate, pm

Stable angina for medical management

Aspirin 75~150mg od

Statin

+/- Titrate dose↑ to get target cholesterol

ACE-inhibitor in proven CVD

Beta blocker post MI

Beta blocker-no prior MI

Add calcium antagonist or long acting nitrate

Consider suitability for revascularization

Clopidogrel 75 mg od

Interchange statins, or ezetimibe with lower dose statin,

or replace with alternative lipid lowering agent

Calcium antagonist** or long acting

Nitrate or K channel opener or If inhibitor

Either substitute

alternative subclass of

calcium antagonist or

long acting nitrateCombination of nitrate and calcium

Antagonist or K channel opener

Level of evidence

Prognosis Symptoms

Symptoms not controlled after

dose optimisation


dose optimisation

Contraindication

(e.g. aspirin allergic)

Intolerant or

contraindication

Intolerant (e.g. fatigue) or contraindicatiion*


dose optimisation

Intolerant

Symptoms not controlled on 2 drugs after dose optimisation

Immediate

short term

relief

Treatment

aimed at

relief of

symptoms

Treatment

aimed at

improving

prognosis

B

A

B

A

B/C

A/B

A

B

A

A

A/B

B/C

Fox K et al. ESC Guideline. Eur Heart J 2006




Medical Therapy

Fraker TD. J Am Coll Cardiol 2007

Lifestyle modificationsWeight controlIncreased physical activity (30 – 60 minutes/day)Stop smokingModeration of alcohol consumptionLimited sodium intakeMaintenance of a diet high in fresh fruits, vegetables

I-B

BP control: < 140/90 mm Hgor < 130/80 mm Hg for DM or CKD

I-A

Dietary therapy for lipid management I-B-

LDL < 100 mg/dl (< 70 mg/dl) I-A (IIa-A)

OMEGA-3 IIb-B

DM control to achieve a near-normal HbA1c I-B

ACC/AHA Guideline 2007 for Chronic Angina




Medical Therapy

Fraker TD. J Am Coll Cardiol 2007

Aspirin: 75 to 162 mg per day indefinitely I-A

ACEI: all patients with LVEF < 40%, HT, DM, CKD

and reasonable for lower-risk patients

I-A

IIa-B

ARB: indicated for ACEI but intolerant of ACEI I-A

Aldosterone blockade: post-MI patients with ACEI and a beta blocker, have LVEF < 40% and with either DM or CHF

I-A

Beta-blocker: MI, ACS, LV dysfunction I-A

Annual influenza vaccination I-B

Chelation therapy III-C

(HT = hypertension, DM = diabetes mellitus, CKD = chronic kidney disease

ACS = acute coronary syndrome, CHF = congestive heart failure)

ACC/AHA Guideline 2007 for Chronic Angina




ACE inhibitors for All Patients?

HOPE Trial (N=9,297)

Patients with vascular disease or

diabetes + one other cardiovascular risk

factor without a low EF or CHF

MI, stroke, or CV death (%)

Relative risk, 0.78; 95 % CI, 0.70 to 0.86

P




Pharmacological Agents to

Reduce Symptoms and Ischemia

Drug Action Comments Recommendations

Short-acting nitrates - Venodilatation

- ↓Diastolic filling

- ↓Reduced intracardiac pressure

- ↓Subendocardial perfusion

- Sublingual administration

- Situational prophylaxis1-C

Long-acting nitrates - Maintain a nitrate-free period 1-C

Beta-blockers

-↓Oxygen demand by ↓heart rate

-↓Contractility

-↓Blood pressure

- Mainstay of therapy

- Long acting 1-selective agents preferred

- Particular for patients with hypertension and tachycardia

- May worsen vasospastic angina

1-A

Calcium channel blockers

- Systemic and coronary vasodilation by inhibition of calcium influx by L-type channels

- Verapamil and diltiazem also reduce myocardial contractility

- Efficacy comparable to beta-blockade

- Particularly effective in vasospastic angina

1-A

Potassium channel opener

- Activate potassium channels

- Also has nitrate-like vasodilator effects- Nicorandil shown to reduce death 1-C

Ivabradine- selectively inhibits the primary pacemaker current in the sinus node

- In patients with -blocker contraindications

IIa-B

Trimetazidine- Exerts metabolic effects without hemodynamic changes

- In patients refractor to other medications

IIb-C

Ranolazine- Exerts antianginal effects by inhibiting the late sodium current

Did not reduce CV events in the MERLIN-TIMI 36 study

IIb-C

Modified from ESC Guideline. Eur Heart J 2006




Medical vs. PCI




PCI for the Patients with Chronic Angina

Bucher, BMJ 2000

• Meta-analysis PTCA vs. Medical Therapy in 6 trials

• 1,563 pt between 1992-1999

End point Risk ratio (95% CI)

Death 1.32 (0.65-2.70)

Angina 0.70 (0.50-0.98)

CABG 1.59 (1.09-2.32)

PTCA 1.29 (0.71-3.36)

MI 1.42 (0.90-2.25)

Favors PTCA Favors Medical Rx

0.4 0.6 0.8 1 2 3

CP1051491-1




Optimal Medical Therapy vs. PCICOURAGE Trial

(%)

Death MI Death/MI Death/MI

CVA

Revascularization

DES used in 2.7%

Boden, NEJM 2007

N=2,287

1 EP




Medical Therapy vs. PCIMeta-Analysis

Schoemig A, J Am Coll Cardiol 2008

N=7,513 from 17 RCTs



Cardiac & Vascular Center Reductions in Mortality with Modern

Therapies in Patients with CAD

Kastrati A, TCT 2009




PCI vs. CABG




Arterial Revascularization Therapy Study (ARTS)

1 Year ResultsStenting(n=600)

CABG(n=605)

P value

Death (%) 2.5 2.8 NS

Stroke (%) 1.7 2.1 NS

MI (%) 6.2 4.8 NS

Repeated revascularization 16.8 3.5




PCI vs. CABG in Multi-vessel Disease

Meta-analysis (N=7812), from 10 trials

◦ 6 trials with balloon angioplasty, 4 trials with BMS

Hlatky MA, Lancet 2009

Mortality




Multi-vessel Disease in DES EraSMC Experience (DES N=441, CABG N=390)

90

92

94

96

98

100

0 1 2 3

p=0.882

CABG

DES

90

92

94

96

98

100

0 1 2 3

p=0.547

CABG

DES

75

80

85

90

95

100

0 1 2 3

p



Cardiac & Vascular Center CABG vs. PCI

in Multivessel and Left Main Disease

Broad Inclusion criteria

◦ Inclusion criteria

LM or 3-VD

◦ Exclusion criteria

Previous PCI

AMI

Other cardiac surgery

SYNTAX Score

Serruys P. NEJM 2009

SYNTAX Trial




CABG vs. PCI by SYNTAX Score in 3VD Subset

Serruys P. NEJM 2009

PCI is comparable to

CABG in the patients with

non-complex lesions.




Indication of Revascularization




Indication of PCI

Class I

◦ Significant lesion AND

◦ High likelihood of success AND

◦ Low risk of morbidity and mortality AND

◦ Large area of viable myocardium

Class IIa

◦ Same anatomic requirements AND

◦ Moderate size of viable myocardium OR

◦ Patients with treated diabetes

Smith Jr SC, ACC/AHA guideline, JACC 2001




Lesions Not To Treat

Insignificant stenosis Small area of myocardium

Low success rate



Cardiac & Vascular Center COURAGE Nuclear SubstudyThe amount of ischemia is crucial

N=314, serial myocardial SPECT◦ An ischemia reduction was associated with a significant

reduction of death or MI. The magnitude of residual ischemia was proportional to the risk.

Impact of Residual IschemiaImpact of Ischemia Reduction

Shaw LJ, Circulation 2008



Cardiac & Vascular Center What is significant?Anatomical vs. Functional

Tonino, JACC 2010, Pijls, JACC 2010

• FAME study, N=1,239 (CAG vs. FFR-based PCI)

FAME 2Y FU

Angiographic stenosis is a poor

indicator of ischemiaFFR-based angioplasty was associated with

a better clinical outcome compared to

angiography-based angioplasty.




Case 1. M/56

Resting chest pain 5 days ago

Hypertension (+), diabetes (+), smoking (-)

Echo: normal wall motion and systolic function

Exercise stress echo: Negative




Case 1. M/56

What I did was

◦ Coronary angiography to see if the CT finding is true or not.




Case 1. M/56

Balloon angioplasty (2.5 mm), which is inexpensive, quick, and does not

need long-term antiplatelet therapy.

The patient discharged on the day of PCI




Case 2. F/71

F/71

Presented with exertional chest pain CCSC II

for 1 year, which was aggravated to CCSC III

since 1 month ago

Risk factors

◦ Hypertension (+), diabetes (-), smoking (-)

Echocardiography

◦ Normal LV function, anterior wall hypokinesia

Pt. No. 25686693




Case 2. F/71

Baseline CAG

Pt. No. 25686693




Case 2. F/71

Promus Element 2.75X28 mm Promus Element 2.5X48 mm

Pt. No. 25686693




Case 2. F/71

Final CAG

Pt. No. 25686693




Case 2. F/71

Pressure wire FFR for

diagonal artery = 0.69

(functionally significant)

I decided to leave it

considering the poor

exercise capacity of the

patients.

The patient has been

doing well without

symptoms for 1 year, so

far.




Clinical Decision for Revascularization

Stenosis severity

Microvascular function

Ischemic area at risk

Functional capacity

Stenosis severity

Microvascular function

FFR

CFR

SPECT

Dobutamine echo

Symptoms

Treadmill test

Stenosis severity CAG

IVUS/OCT

CT angiography

Determinants Assessment

Clinical Significance

Functional Significance

Anatomical Significance

Patients

Myocardium

Coronary artery

Treatment Goal




Antiplatelet Therapy

after DES Implantation




Cypher Cordis

Taxus Boston Scientific

Endeavor Medtronic

Endeavor Resolute Medtronic

Xience/Promus Abbott / Boston Scientific

Promus Element Boston Scientific

Nobori Terumo

Cypher Taxus Endeavor Xience Promus element Nobori




Meta-analysis: DES and BMS

Increased risk of stent thrombosisafter 1 year following DES implantation

After 1 year,

SES 0.6%, BMS 0.05%

p=0.02

Kastrati A, NEJM 2007

5-year Death or MI (N=4,958)




Wenaweser P, WCC 2006

Incidence of DES Stent Thrombosis

Bern - Rotterdam Cohort Study

Cu

mu

lati

ve p

rob

ab

ilit

y o

f ste

nt

thro

mb

osis

(%

)

Days after stent implantation

0 200 400 600 800 1000 1200

0

1

2

3 N=8,146 Patients

Patients at risk (n)

Cumulative incidence (%)

Days after stenting

2.92.31.71.2

1095730365309

1.1

9712841533970028146 7162




Premature Discontinuation of Antiplatelet Therapy

: Most Important Predictor of Stent Thrombosis

Iakovou

JAMA 2005

Park

AJC 2006

Kuchulakanti

Circulation 2006

Airoldi

Circulation 2007

OR=89.8

(29.9-27.0)

HR=19.2

(5.6-65.5)

OR=4.8

(2.0-11.1)

HR=13.7

(4.0-46.7)




Early Discontinuationwas the Most Important Predictor of Stent Thrombosis

Duke Database 6-month landmark analysis for Death/MI

Eisenstein EL, JAMA 2007

DES with clopidogrel

DES without clopidogrel

BMS without clopidogrel

BMS with clopidogrel

Adjusted 24-mo outcome

DES p=0.02

BMS p=0.70




ACC/AHA PCI Guidelines 2007Duration of Dual Antiplatelet Therapy (DAT) for DES

Class I

◦ All patients receiving a DES, clopidogrel 75 mg daily should be

given for at least 12 months if patients are not at high risk of

bleeding. (LoE B)

Class IIb

◦ Continuation of clopidogrel therapy beyond 1 year may be

considered. (LoE C)




ACC/AHA Guideline Focused Update 2009Duration of Dual Antiplatelet Therapy (DAT) for DES

Class I

◦ If the risk of morbidity because of bleeding outweighs the anticipated

benefit, earlier discontinuation should be considered. (LoE C)

Class I

◦ In patients with ACS, clopidogrel 75 mg or prasugrel 10 mg daily

should be given for at least 12 months (LoE B)

Class IIb

◦ Continuation of clopidogrel or prasugrel beyond 15 months may be

considered in patients undergoing DES placement. (LoE C)




Annual Bleeding Risk of DAT

N=87,205 from 13 stroke studies

Usman MH, Am J Cardiol 2009

4.8%2.9% 1.0%

10.1%

0.9%

Annual Total Bleeding Annual Major Bleeding

1.8%

5.3% 0.8%

(DAT = dual antiplatelet therapy)




No increased risk by the discontinuation of

clopidogrel after 6 months: J-Cypher Registry

Kimura T, Circulation 2009

Adjusted Risk of Death or MI

6-month Landmark analysis



Cardiac & Vascular Center Merged Analysis of

ZEST-LATE and REAL-LATE

N=2701, randomized to DAT or aspirin alone between 12-24 months

The use of DAPT > 12 months after DES implantation was not more effective than aspirin alone in reducing the rate of cardiac death or MI.

Park SJ, NEJM 2010




Trial name Subjects DAT duration DES type 1 EP

DAPT20,645

12-mo event free12-mo vs. 30-mo All DES and BMS 33-mo D/MI/CVA

ISAR-SAFE6,000

6-mo event free6-mo vs. 12-mo All DES 15-mo D/MI/CVA/Bleed

CYPRESS2,500

All comer12-mo vs. 30-mo All DES D/MI

OPTIDUAL1,966

All comer12-mo vs. longer All DES 3-year D/MI/CVA/Bleed

SCORE280

Myocardial infarction12-mo vs. 24-mo All DES 1-year D/MI

OPTIMIZE3,120

Non-STEMI3-mo vs. 12-mo ZES 12-mo D/MI/CVA/Bleed

PRODIGY1,700

All-comer6-mo vs. 24-mo EES, PES, ZES, BMS 24-mo D/MI/CVA

Ongoing RCTs on Duration of DAT

DAT = dual antiplatelet thearpy, EP = end point,

D/MI/CVA = death, myocardial infarction, cerebrovascular accident

(from www.clinicaltrials.gov)




EXCELLENT TrialProspective, open label, two-arm, randomized multi-center trial

1mo 3mo 9mo 12mo

Clinical

Angiographic

3yr2yr 4yr 5yr

Primary endpoint

Target vessel failure

Co-primary angiographic

endpoint evaluation

DAT 6 monthsN=722

DAT 12 monthsN=721

1443 Patients Matching

Enrollment Criteria

EESN=540

SESN=182

EESN=539

SES

N=182

Percutaneous Coronary Intervention

2x2

factorial design

Gwon HC, Will be presented at LBCT in ACC 2011

www.clinicaltrials.gov (NCT00698607).




Conclusions

Rules to select therapeutic options

◦ Make a clinical decision, not only based on anatomical and functional evidences.

◦ Considering the benefit-to-risk ratio

The benefit of the treatment

Reduction of the risk of death or MI

Improvement of left ventricular function

Improvement of symptom and functional capacity

The risk of the treatment

Periprocedural events

Long-term risk of bleeding, stent thrombosis

Cost

Documents

Hyeon-Cheol Gwon · 2013. 7. 23. · Merck Regional Cardiology Symposium 2011 ... CHF = congestive heart failure) ACC/AHA Guideline 2007 for Chronic Angina. Merck Regional Cardiology