hyeon-cheol gwon · 2013. 7. 23. · merck regional cardiology symposium 2011 ... chf = congestive...
TRANSCRIPT
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Hyeon-Cheol Gwon
Cardiac and Vascular Center, Samsung Medical CenterSunkyunkwan University School Medicine
Samsung Medical Center
Cardiac & Vascular Center
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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)
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Medical Therapy
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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.
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
Symptoms not controlled after
dose optimisation
Contraindication
(e.g. aspirin allergic)
Intolerant or
contraindication
Intolerant (e.g. fatigue) or contraindicatiion*
Symptoms not controlled after
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Medical vs. PCI
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Medical Therapy vs. PCIMeta-Analysis
Schoemig A, J Am Coll Cardiol 2008
N=7,513 from 17 RCTs
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center Reductions in Mortality with Modern
Therapies in Patients with CAD
Kastrati A, TCT 2009
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
PCI vs. CABG
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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.
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Indication of Revascularization
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Lesions Not To Treat
Insignificant stenosis Small area of myocardium
Low success rate
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
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.
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Case 1. M/56
Resting chest pain 5 days ago
Hypertension (+), diabetes (+), smoking (-)
Echo: normal wall motion and systolic function
Exercise stress echo: Negative
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Case 1. M/56
What I did was
◦ Coronary angiography to see if the CT finding is true or not.
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Case 2. F/71
Baseline CAG
Pt. No. 25686693
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Case 2. F/71
Promus Element 2.75X28 mm Promus Element 2.5X48 mm
Pt. No. 25686693
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Case 2. F/71
Final CAG
Pt. No. 25686693
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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.
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
Antiplatelet Therapy
after DES Implantation
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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)
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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)
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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)
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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)
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Merck Regional Cardiology Symposium 2011
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Cardiac & Vascular Center
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)
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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
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Merck Regional Cardiology Symposium 2011
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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
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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)
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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).
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Merck Regional Cardiology Symposium 2011
Samsung Medical Center
Cardiac & Vascular Center
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