Managing Risk of Acs

8/12/2019 Managing Risk of Acs

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CURRICULUM VITAEDr. Muhammad Aminuddin SpJP K)-FIHA

Nama : Dr.Muhammad Aminuddin SpJP(K)-FIHAJabatan : 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 SurabayaAlamat 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 2000Riwayat 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 /RSUDDr Soetomo Surabaya ( 20011 Sekarang)


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Managing Risk of Patients withAcute Coronary Syndome:

What Should We Do?

Dr. M. Aminudin, SpJP (K) FIHADepartemen /Kardiologi dan Kedokteran

VaskulerRSU. Dr. Soetomo / FK-UNAIR

Surabaya


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ACUTE CORONARY SYNDROME

No ST Elevation ST Elevation

Unstable Angina NQMI

NSTEMI

Classification of ACS

QMI

ECG

Manangement

HistoryPhysical Exam


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Character of myocardial ischemia


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Vulnerable Plaque

Platelet cascadeThrombus formationVasospasm

Plaque rupture(55-80%)

ExertionBP, HR

Vasoconstriction

Pathophysiology

Acute MI

Complete occlusion

Unstable angina

Non-Q MI

Incomplete occlusionDistal embolization

Healingplaque

Spontaneous lysis


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Platelet cascade


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Thrombus formation

Factor

VII

Factor

XaProthrombin

Thrombin

(II)Fibrinogen

Fibrin

Promotes:

n Tissue factorsnAdhesive molecules

n Smooth muscle

n Leukocyte activation

n Platelet aggregation

n Release reaction


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Vasospasm

Endothelium as an organ 1 to 6 x 1013cells monolayer

weighs 1 kg

covers 6 tennis courts

Modulator of vascular tone nitric oxide (NO)

prostaglandin I2 (PGI2,prostacycline)

Endothelin-1

TXA2

Regulator of hemostasis antithrombotic

prothrombotic

AnticoagulantGAGs/AT III

TFPI

Thrombomodulin

Profibrinolytict-PA

u-PA

Binding sites forplasminogenPA receptorsPlatelet inhibitoryPGI2(prostacycline)

Nitric oxideADPase

Carbon monoxide

ProcoagulantTissue factor

Binding sites forcoagulation factorsand fibrinAntifibrinolyticPAI

TAFIPlatelet activatingvWF

PAF

FibronectinEndothelin-1

TXA2

AntithromboticVasodilation ProthromboticVasoconstriction


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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


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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;109:433 8.

Risk Factor Assesment According to AHA


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Principle ofACS management

Revascularization Medical

Balloon

CABG Medication for ischemia

Modified risk factors

Treatment of complicationFactor of revascularization

decrease area infarctionprevent LV dysfunctiondecrease mortality

TIME IS MUSCLE ANDMUSCLE IS TIME

Timing of symptoms Timing of treatments

Patient condition

Medical limitation Instrument limitation

Personal limitation


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Principle of ACS management

ACS

AspirinNitrates

MoBeta blockersACEIAntithrombinClopidogrelGPII/IIIa

Early InvasivePrimary PCIFacilitate PCIRescue PCICABG

Early ConservativeFibrinolytic drugs

Risk stratification

HemodynamicstabilizationMedicalVentilatorIABPPace maker

Elective CAG+/- PCI or CABG

Adjuvant Rx
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Medication of ACS

Fibrinolytic agents

Antinthrombotic agentsAnti-platelet therapy

aspirin, ticlopidine, clopidogrel, GP IIb/IIIainhibitors

Anti-coagulant therapy

heparin, low molecular weight heparin(LMWH)

Antiischemic agentsActivity, Oxygen

Morphine, Nitrates, Beta blockers

Others:ACEIs, ARBs, Statins, Fibrates


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Indication of invasive management

Early and possible to invasive Rx.

Contraindication of fibrinolytic drugs

Consent from patient and relative

ComplicatedAMI

Cardiogenic shock

VSD, MR

Electrical instability


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Percutaneous coronary angioplasty


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Primary PCI and Lytic Therapy

Death Reinfarction Death Reinfarction30 days 6 months

** *

Grines CL. Circulation 1999


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Risk & Benefit of PCI

Benefit Reduce

Mortality (Death, MI) Nonfatal MI

Reinfarction Rehospitalization

Effect in short and longterm 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 Open24 hrs Policy


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Indication ofPrimary PCI

Angina within 3 hrs and expectedDTBDTN less than 1 hr

Angina after 3 hrs

Severe CHF within 12 hrs of angina (I) or12-24 hrs of angina(IIa)

Shock within 36 hrs of angina (I) andrecommend PCI within 18 hrs ofshock


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Non-Primary PCI

Rescue PCI Shock with in 36 hrs of

MI (PCI within 36 hrs ofshock)

Pt age < 75 yrs (I) Pt age 75 yrs (IIa)

Severe CHF and onset ofsymptoms 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%) orserious ventricular

arrhythmia (IIa) Routine PCI after

fibrinolysis (IIb)


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Coronary Arterial Bypass Graft


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Indication for CABG

Fail or contraindication toPCI or Fibrinolytic drugs

Lesion is not suitable to PCI LM disease Triple disease

Complicated AMI acute severe MR

Rupture LV, VSD


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Risk Factor Modification

Smoking Cessation 2.5 increased mortality riskreduced 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


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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 of60bpm


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Secondary Prevention (continued)

ACE Inhibitors LVF patientsmortality 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


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Medications Post-surgicalIntervention

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-stentthen low dose aspirin indefinitely[CLASSICS]


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Therapeutic Life Style Changes

Nutrient Recommended intakeTotal 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


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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%

DietaryAdjuncts: Efficacy at ReducingLDL-C

Jones PJ. Curr Atheroscler Rep1999;1:230-235

Lichtenstein AH. Curr Atheroscler Rep1999;1:210-214

Rambjor GS et al. Lipids1996;31:S45-S49

Ripsin CM et al. JAMA1992;267:3317-3325


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Therapeutic Life Style Changes

Other l i fe sty le changes inc lude:

Weight reduction specially in overweight

patients (reduce 10% in the first 6 months)

Increase physical activity

Smoking cessation


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Drug Therapy for Dyslipidemia

Bile acid resins

Ezetimibe

Niacin

Statins

Fibric acid derivatives

Fish oil

Postmenopausal drug therapy


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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 requirehigher doses for TG

For many patients with mixedhyperlipidemia can use a moderate doseof statin (to avoid side effects of higherdoses) with combination of either niacin,

resin, ezetimibe or fibrates


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Normal LDL value but Low HDL:

Drug of choice: Niacin or fibratesIf patient have normal LDL OR

patient within LDL goal on statintherapy but still HDL high add niacin

or fibrates


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Elevated TGs value:

Drug of choice: Fibrates & niacin

Can add fish oil If only TG level is high


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4. Plaque rupture,cholesterol content,inflammation (hs-CRP)(statins)

3. Platelet adhesion/activation/aggregation(aspirin, clopidogrel,

GP IIb/IIIa inhibitors)

2. Activation of clotting

cascadethrombin(heparin/LMWH)

1. Downstream from thrombusmyocardial ischaemia/necrosis(-blockers, nitrates etc)

Platelet

GP IIb/IIIa

receptor

FibrinogenThrombin

Fibrin

clot

Pathophysiology of ACS and potentialpharmacological interventions


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Statins*LDL-C reduction

Reduction in

chylomicron and

VLDL remnants,

IDL, LDL-C

Restore endothelialfunction

Maintain SMC function

Anti-inflammatory effects

Decreased thrombosis

Lumen

Lipid

core

Macrophages

Smooth

muscle

cells

Potential mechanisms of benefit ofstatins in ACS

*Statins differ

significantly

in terms of these

effects/mechanisms


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LDL-Rmediated

hepatic uptake ofLDL 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 CirculationHepatocyteThe 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

VLDLR

VLDL

ATORVASTATIN : HMG-CoA Reductase Inhibitor

Mechanism of Action


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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 Biol2001;21:1712-1719.


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Risk factor LDL-C

0 1 < 160 mg/dl2 < 130 mg/dl

CHD and CHD riskequivalent < 100 mg/dlVery 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/dlHDL-C > 40 mg/dlTriglyceride < 150mg/dl


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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 perm


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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


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Source: Pfizer Inc. Data on file. Review of 44 completed clinical trials.

Atorvastatin Experience : Clinical Safety Data

Digestive 4 8 9Body as a whole 5 5 6Musculoskeletal 1 3 4Nervous 2 3 3

Skin and appendages 1 2 2Metabolic/Nutritional 1 1 1Special senses < 1 1 < 1Urogenital 1 1 1Cardiovascular 2 1 1

Bodysystem

Placebon = 1789

Atorvastatin(all doses)n = 9416

All otherstatins combined

n = 5290

(%)

Treatment-Associated AEs 1% of Patients

(%) (%)


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Atorvastatin Experience :

Clinical Safety Data

ALT/AST elevations > 3x ULN :

0.5% of patients treated with atorvastatin 10 to 80mg experienced ALT/AST elevations > 3x ULN.

Myalgia

Incidence of myalgia across all the atorvastatin

doses was low (1.9%) and directly comparable tothe incidence of myalgia observed in patients

receiving other statins combined.

Source: Pfizer Inc. Data on file. Review of 44 completed clinical trials.


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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


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Risk Factors for CVD include Dyslipidemia

LDL C is the mayor lipid risk factor fordevelopment and progression of CVD

LDL C reduction has been shown toimprove cardio vascular mortality andmorbidity

Statin are now clearly established as firstline drug for treatment patient withhypercholesterolaemia

Atorvastatin was proven to be effectiveand save


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Managing Risk of Acs

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