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CURRICULUM VITAE
Dr. Muhammad Aminuddin SpJP(K)-FIHA
Nama : Dr.Muhammad Aminuddin SpJP(K)-FIHA
Jabatan : Ka Dept/SMF Kardiologi dan kedokteran vaskuler
FK Unair / RSUD Dr Soetomo Surabaya
Alamat Kantor : Dept/SMF Kardiologi dan kedokteran
Vaskuler FK Unair-RSU Dr. Sutomo Surabaya
Jln. Mayjen Prof. Dr. Mustopo 6-8 Surabaya
Alamat rumah : Jl. Manyar Kertoarjo I/7, Surabaya
Pendidikan :
- Dokter FK Universitas Airlangga : Th.1980
-Spesialis Ilmu Penyakit Jantung & Pembuluh Darah : Th. 1994
-Course in Cardiology : Osaka, Jepang th 2000
Riwayat Jabatan :
- SPS Bag /SMF Kardiologi dan Kedokteran Vaskluler FK Unair
/RSUD Dr. Soetomo
Surabaya(2006 2011)
- Ka Dept/SMF Kardiolgi dan kedokteran vaskuler FK Unair /RSUD
Dr Soetomo Surabaya ( 20011 Sekarang)

Managing Risk of Patients with
Acute Coronary Syndome:
What Should We Do?
Dr. M. Aminudin, SpJP (K) FIHA
Departemen /Kardiologi dan Kedokteran
Vaskuler
RSU. Dr. Soetomo / FK-UNAIR
Surabaya
ACUTE CORONARY SYNDROME
No ST Elevation ST Elevation
Unstable Angina
NQMI

NSTEMI
Classification of ACS
QMI
ECG
Manangement
History
Physical Exam
Character of myocardial ischemia
Vulnerable Plaque
Platelet cascade
Thrombus formation
Vasospasm
Plaque rupture
(55-80%)
Exertion
BP, HR
Vasoconstriction
Pathophysiology
Acute MI
Complete occlusion
Unstable angina
Non-Q MI
Incomplete occlusion
Distal embolization
Healing
plaque
Spontaneous lysis
Platelet cascade
Thrombus formation
Factor
VII
Factor
Xa
Prothrombin
Thrombin
(II)
Fibrinogen
Fibrin
Promotes:
n Tissue factors
n Adhesive molecules
n Smooth muscle
n Leukocyte activation
n Platelet aggregation
n Release reaction
Vasospasm
Endothelium as an organ
1 to 6 x 10
13
cells monolayer
weighs 1 kg
covers 6 tennis courts
Modulator of vascular tone
nitric oxide (NO)
prostaglandin I
2
(PGI
2
,
prostacycline)
Endothelin-1
TXA2
Regulator of hemostasis
antithrombotic
prothrombotic
Anticoagulant:
GAGs/AT III
TFPI
Thrombomodulin
Profibrinolytic:
t-PA
u-PA
Binding sites for
plasminogen
PA receptors
Platelet inhibitory:
PGI
2
(prostacycline)
Nitric oxide
ADPase
Carbon monoxide
Procoagulant:
Tissue factor
Binding sites for
coagulation factors
and fibrin
Antifibrinolytic:
PAI
TAFI
Platelet activating:
vWF
PAF
Fibronectin
Endothelin-1
TXA
2

Antithrombotic
Vasodilation
Prothrombotic
Vasoconstriction
Risk Factors for Cardiovascular
Disease
Modifiable
Smoking
Dyslipidaemia
raised LDL cholesterol
low HDL cholesterol
raised triglycerides
Raised blood pressure
Diabetes mellitus
Obesity
Dietary factors
Thrombogenic factors
Lack of exercise
Excess alcohol consumption
Non-modifiable
Personal history
of CHD
Family history
of CHD
Age
Gender
Major Risk Factors Additional Risk Factor
Cigarette smoking Small LDLparticle
Elevated blood pressure Ethnic characteristic
Elevated LDL & Total Cholesterol Psychososial factors
Low HDL Elevated TG
Diabetes mellitus Glucose intolerance
Obesity (abdominal obesity) Elevated homocysteine
Inactivity Elevated lipoprotein (a)
Family history of premature CAD Prothrombotic factor (fibrinogen)
Advancing age Inflamatory marker (CRP)
Grundy SM, et al. Assessment of cardiovascular risk by use of multiple-risk-factor assessment
equations. Circulation. 1999;100:148192.
Grundy SM, et al. Definition of metabolic syndrome. Circulation. 2004;109:4338.
Risk Factor Assesment According to AHA
Principle of ACS management
Revascularization
Medical
Balloon
CABG
Medication for ischemia
Modified risk factors
Treatment of complication
Factor of revascularization
decrease area infarction
prevent LV dysfunction
decrease mortality
TIME IS MUSCLE AND
MUSCLE IS TIME
Timing of symptoms
Timing of treatments
Patient condition
Medical limitation
Instrument limitation
Personal limitation
Principle of ACS management
ACS
Aspirin
Nitrates
Mo
Beta blockers
ACEI
Antithrombin
Clopidogrel
GPII/IIIa
Early Invasive
Primary PCI
Facilitate PCI
Rescue PCI
CABG
Early Conservative
Fibrinolytic drugs
Risk stratification
Hemodynamic
stabilization
Medical
Ventilator
IABP
Pace maker
Elective CAG
+/- PCI or CABG
Adjuvant Rx
Medication of ACS
Fibrinolytic agents
Antinthrombotic agents
Anti-platelet therapy
aspirin, ticlopidine, clopidogrel, GP IIb/IIIa
inhibitors
Anti-coagulant therapy
heparin, low molecular weight heparin
(LMWH)
Antiischemic agents
Activity, Oxygen
Morphine, Nitrates, Beta blockers
Others: ACEIs, ARBs, Statins, Fibrates
Indication of invasive management
Early and possible to invasive Rx.
Contraindication of fibrinolytic drugs
Consent from patient and relative
Complicated AMI
Cardiogenic shock
VSD, MR
Electrical instability
Percutaneous coronary angioplasty
Primary PCI and Lytic Therapy
Death Reinfarction Death Reinfarction
30 days 6 months
*
*
*
Grines CL. Circulation 1999
Risk & Benefit of PCI
Benefit
Reduce
Mortality (Death, MI)
Nonfatal MI
Reinfarction
Rehospitalization
Effect in short and long
term outcome
Risk of PCI
Death 0-2%
MI 3-5%
Emergency CABG 3-7%
Stroke 0-1%

Limitation
LM disease
Diffuse disease
3 VV disease
Personal resource
Interventionist
Cath-lab nurse
ED staff
Team of primary
care
Open 24 hrs
Policy
Indication of Primary PCI
Angina within 3 hrs and expected
DTB DTN less than 1 hr

Angina after 3 hrs

Severe CHF within 12 hrs of angina (I) or
12-24 hrs of angina (IIa)

Shock within 36 hrs of angina (I) and
recommend PCI within 18 hrs of shock
Non-Primary PCI
Rescue PCI
Shock with in 36 hrs of
MI (PCI within 36 hrs of
shock)
Pt age < 75 yrs (I)
Pt age 75 yrs (IIa)
Severe CHF and onset of
symptoms within 12 hrs
Symptoms 12-24 hrs
(IIa) with
Hemodynamic or electrical
instability
Persistent ischemia
PCI after Fibrinolysis
Recurrent of ischemia
(Fail fibrinolysis)
Cardiogenic shock or
hemodynamic instability
Serious CHF (IIa)
Poor LVEF ( 40%) or
serious ventricular
arrhythmia (IIa)
Routine PCI after
fibrinolysis (IIb)
Coronary Arterial Bypass Graft
Indication for CABG
Fail or contraindication to PCI or
Fibrinolytic drugs
Lesion is not suitable to PCI
LM disease
Triple disease
Complicated AMI
acute severe MR
Rupture LV, VSD
Risk Factor Modification
Smoking Cessation
2.5 increased mortality risk reduced if quit
Diet modification
Low fat, low cholesterol
Hypertension
Poorly controlled BP increases mortality risk
Diabetes
Tight control, metformin if obese
Cardiac rehab (with exercise)
Mortality benefits, Quality of Life
Secondary Prevention
Aspirin
Continue indefinitely
Benefits established to 27 months (death,
non-fatal MI/stroke - ARR 4%)

Betablockers
Continue indefinitely
Long-term mortality benefits shown [BHAT, ISIS-1]
Titrate dose (according to BP) to HR of
60bpm

Secondary Prevention (continued)
ACE Inhibitors
LVF patients mortality reduction at 1 to 5 yrs
Patients without LVF reduction in mortality,
MI, stroke (often initiated months after MI)
[HOPE]
Lipid therapy
Statins have shown long-term mortality
benefits
Targets
LDL < 70 mg/dl
Medications Post-surgical
Intervention
CABG (Coronary Artery Bypass Graft)
anti-anginal medications usually ceased
continue secondary prevention medications

PTCA (Percutaneous Transluminal
Coronary Angioplasty) + Stent Insertion
continue clopidogrel and higher dose
(300mg) aspirin daily for 9 month post-
stent then low dose aspirin indefinitely
[CLASSICS]
Therapeutic Life Style Changes
Nutrient Recommended intake
Total fat 25-35% of total calories
Saturated fate < 7% of total calories
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories
Carbohydrates 50-60% of total calories
Fiber 20-30 g/day
Cholesterol < 200 mg/day
Protein 15% of total calories
Therapy Dose (g/day) Effect
Dietary soluble fiber 2-8 LDL-C 5-10%
Soy protein 20-30 LDL-C 5-7%
Stanol esters 1.5-4 LDL-C 10-15%
Dietary Adjuncts: Efficacy at Reducing
LDL-C
Jones PJ. Curr Atheroscler Rep 1999;1:230-235
Lichtenstein AH. Curr Atheroscler Rep 1999;1:210-214
Rambjor GS et al. Lipids 1996;31:S45-S49
Ripsin CM et al. JAMA 1992;267:3317-3325
Therapeutic Life Style Changes
Other life style changes include:
Weight reduction specially in overweight
patients (reduce 10% in the first 6 months)
Increase physical activity
Smoking cessation
Drug Therapy for Dyslipidemia
Bile acid resins
Ezetimibe
Niacin
Statins
Fibric acid derivatives
Fish oil
Postmenopausal drug therapy
Drugs of Choice for Dyslipidemia
Elevated LDL & TG values:
Drug of choice: Statin
Combination: statin + niacin; statin +
ezetimibe; or statin + resin

It decreases LDL & TG but require
higher doses for TG
For many patients with mixed
hyperlipidemia can use a moderate dose
of statin (to avoid side effects of higher
doses) with combination of either niacin,
resin, ezetimibe or fibrates
Drugs of Choice for Dyslipidemia
Normal LDL value but Low HDL:
Drug of choice: Niacin or fibrates

If patient have normal LDL OR
patient within LDL goal on statin
therapy but still HDL high add niacin
or fibrates
Drugs of Choice for Dyslipidemia
Elevated TGs value:
Drug of choice: Fibrates & niacin
Can add fish oil
If only TG level is high
4. Plaque rupture,
cholesterol content,
inflammation (hs-CRP)
(statins)
3. Platelet adhesion/
activation/aggregation
(aspirin, clopidogrel,
GP IIb/IIIa inhibitors)
2. Activation of clotting
cascade thrombin
(heparin/LMWH)
1. Downstream from thrombus
myocardial ischaemia/necrosis
(-blockers, nitrates etc)
Platelet
GP IIb/IIIa
receptor
Fibrinogen
Thrombin
Fibrin
clot
Pathophysiology of ACS and potential
pharmacological interventions
Statins*
LDL-C reduction
Reduction in
chylomicron and
VLDL remnants,
IDL, LDL-C Restore endothelial
function
Maintain SMC function
Anti-inflammatory effects
Decreased thrombosis
Lumen
Lipid
core
Macrophages
Smooth
muscle
cells
Potential mechanisms of benefit of
statins in ACS
*Statins differ
significantly
in terms of these
effects/mechanisms
LDL-Rmediated
hepatic uptake of
LDL and VLDL
remnants
Serum VLDL remnants
Serum LDL-C
Cholesterol
synthesis
LDL receptor
(BE receptor)
synthesis
Intracellular
Cholesterol
Apo B
Apo E
Apo B
Systemic Circulation Hepatocyte
The reduction in hepatic cholesterol synthesis lowers intracellular
cholesterol, which stimulates upregulation of the LDL receptor and
increases uptake of non-HDL particles from the systemic circulation
LDL
Serum IDL
VLDL
R

VLDL
ATORVASTATIN : HMG-CoA Reductase Inhibitor
Mechanism of Action
Main Effects of Statins
Effects on lipids:
Reduce LDL-C, TC and TG
Increase HDL-C
Pleiotropic effects:
Improve or restore endothelial function
Enhance the stability of atherosclerotic plaques
Decrease oxidative stress
Decrease vascular inflammation
Anti-thrombotic effects
Takemoto M, Liao JK. Arterioscler Thromb Vasc Biol 2001;21:1712-1719.
Risk factor LDL-C
0-1 < 160 mg/dl
2 < 130 mg/dl
CHD and CHD risk
equivalent
< 100 mg/dl
Very high risk 70 mg/dl
NCEP-ATP III Report. JAMA 2001;285:2486-2497
Grundy SM, et al. NCEP Report. Circulation 2004;110:227-239
TARGET LIPID
LDL-C: Primary target of therapy





Total cholesterol < 200 mg/dl
HDL-C > 40 mg/dl
Triglyceride < 150mg/dl
The percentage reduction or elevation of
the various lipid fractions with the different drugs
Drug LDL HDL TG
Resins 15-35% -/ 4 % -/
HMG-CoA reductase 25-40% 5-10% 15-20%
Inhibitors
Fibrates 10-25% 10-15% 50%
Nicotinic acid 15-35% 10-25% 50%
(from Chia reproduced with permission)
Statin Efficacy : LDL-C Reduction
*Simvastatin 80 mg not available at time of study.
**Significantly greater than mg-equivalent doses of
comparative agents (P .01).

Significantly less than atorvastatin 10 mg (P .02).

Significantly less than atorvastatin 20 mg (P .01).

Jones P, et al, for the CURVES Investigators. Am J Cardiol. 1998;81:582-587.
Atorvastatin
Simvastatin*
Pravastatin
Lovastatin
Fluvastatin
0 -60 -50 -40 -30 -20 -10
10 mg (n = 73)
20 mg (n = 51)
40 mg (n = 61)
10 mg (n = 70)
20 mg (n = 49)
40 mg (n = 61)
10 mg (n = 14)
20 mg (n = 41)
40 mg (n = 25)
20 mg (n = 16)
40 mg (n = 16)
40 mg (n = 12)
20 mg (n = 12)
-38%**
-46%**
-51%**
-28%

-35%

-41%

-19%

-24%

-34%

-29%

-31%

-17%

-23%

80 mg (n = 10) -54%

80 mg (n = 11)
-48%

% LDL-C reduction
Source: Pfizer Inc. Data on file. Review of 44 completed clinical trials.
Atorvastatin Experience : Clinical Safety Data
Digestive 4 8 9
Body as a whole 5 5 6
Musculoskeletal 1 3 4
Nervous 2 3 3
Skin and appendages 1 2 2
Metabolic/Nutritional 1 1 1
Special senses < 1 1 < 1
Urogenital 1 1 1
Cardiovascular 2 1 1
Body
system
Placebo
n = 1789
Atorvastatin
(all doses)
n = 9416
All other
statins combined
n = 5290
(%)

Treatment-Associated AEs 1% of Patients

(%)


(%)

Atorvastatin Experience :
Clinical Safety Data
ALT/AST elevations > 3x ULN :
0.5% of patients treated with atorvastatin 10 to 80
mg experienced ALT/AST elevations > 3x ULN.

Myalgia
Incidence of myalgia across all the atorvastatin
doses was low (1.9%) and directly comparable to
the incidence of myalgia observed in patients
receiving other statins combined.
Source: Pfizer Inc. Data on file. Review of 44 completed clinical trials.
Conclusions
CHD is leading cause of mortality and was
responsible for approximately 30% of deaths
Principle management of ACS include
Revascularization
Medical
Balloon
CABG
Medication for ischemia
Modified risk factors
Treatment of complication
Risk Factors for CVD include Dyslipidemia
LDL C is the mayor lipid risk factor for
development and progression of CVD
LDL C reduction has been shown to
improve cardio vascular mortality and
morbidity
Statin are now clearly established as first
line drug for treatment patient with
hypercholesterola emia
Atorvastatin was proven to be effective
and save


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