SINDROMA KORONER AKUT- S K A –

• - NYERI DADA• - CHEST DICOMFORT• - O.K. ISKEMIA MIOKARD

NYERI DADA :

• UNSTABLE ANGINA• NON Q WAVE– IMA• IMA

PENATA LAKSANAAN

NYERI DADA TYPCAL - PERTAMA KALI - 6 MIGGUEKG : ST ISKEMI /ELEVATIONENZIM: TROPONIN T / I + C K-MB / DLL MENINGKAT

INFARK MIOKARD AKUT

PENDAHULUAN PENATALAKSANAAN SEDINI MUNGKIN SANGAT PENTING - 30 - 60 MENIT PERTAMA -TERAPI TROMBLITIK DEFINISI - KETIDAK SEIMBANGAN - NEKROSIS MIOKARD

PATOGENESIS :- SEVERE ATHEROSCLEROTIC 1 /

LEBIH ARTERI KORONER

1. RUPTURNYA PLAQUE ( FISSURE/ PERDARAHAN )

2. SPASME/ EMBORI KORONER ( KOKAIN )

PENCEGAHAN

PADA JAM ² PERTAMA :- TRANSMURAL ----> TROMBROSIS TERAPI TROMBOLITIK :

- PADA IMA TRANSMURAL --( + )

- NONTRANSMURAL-----> ( - ) KEMATIAN: -KETIDAKSTABILAN ELEKTRIK PRE HOSPITAL

MANIFESTASI KLINIS

-59% ISTIRAHAT / TIDUR - 41 % AKTIFITAS- CIRCADIAN 6 AM - NOON - MUSIM DINGIN 15 - 20 %- STRESS EMOSI - FISIK- KEMATIAN , PERCERAIAN, PHK,

STRESS YANG LAMA

DIAGNOSIS IMA : - HARUS SEGERA DITEGAKKAN DAN

DIOBATI 1. NYERI DADA SAAT ISTIRAHAT DAN

AKTIFITAS YANG BIASA2. PERUBAHAN NYERI DADA :

- FREKUENSI - KUALITAS - SERANGAN PERTAMA/

ISTIRAHAT3. NYERI DADA PADA PJK YAG TELAH

DIKENAL YG TIDAK BERKURANG SAAT ISTIRAHAT/ NITRAT

KELUHAN :1. NYERI DADA YG KHAS /

DISCOMFORT :LOKASI, SIFATNYA, PENJALARAN,

LAMANYA, DST2. MENINGKAT DLM BEBERAPA MENIT

UNTUK RESIKO TINGGI 3. NYERI DADA PERTAMA KALI --->

DIEFALUASI - TIDAK BERKURANG 10 MENIT

BILA DIBERI TIGA TABLET NITRAT PADA PENDERITA YG TDK DIKENAL DAN PERLU SEGERA KE IGD

4. PENDERITA DM + IMA --> NYERI DADA - TETAPI SESAK NAFAS

5. WANITA & ORANG TUA --> ATIPIKAL 6. VF : 15 X PADA JAM ² PERTAMA

- 35 % IMA --> VF 7. ONSET SYMTOM SAMPAI

PERTOLONGAN 24 JAM8. PERLU PENDIDIKAN PENUNTUN

UNTUK PENDERITA, KELUARGA, MASYARAKAT

SEMUA UTK MENURUNKAN MORTALITAS PREHOSPITAL

PENATALAKSANAANDIAGNOSIS IMA :1. ANGHINAPEKTORIS > 30 MENIT

TIDAK HILANG DENGAN NITRAT 2. GAMBARAN EKG YG KHAS :

GEL T YG TINGGI, ST ELEVASI, GEL Q

KK : MASIH NORMAL3. ENZIM : CK, CKMB 2X NORMAL

TROP T +

WHO : IMA + : BILA 2 DR 3 KRITERIA+ANAMNESA DAN PEMERIKSAAN FISIK --> 7 - 10 MENITDENGAN DIAGNOSIS YG CEPAT & TEPAT --> TERAPI TROMBOLITIK DAPAT DIPERTIMBANGKAN (INDIKASI DAN KONTRA INDIKASI)

MONITOR EKG : - EKG dan defibrilator penting- PERLU UNTUK DETEKSI VF IV LINES :- SEGERA DIPASANG PD LENGAN

ATAS - HATI- HATI DENGAN VENA YG

TERTEKAN ( VENA SUBCLAV ) OXIGEN:- AKIBAT GANGGUAN PERFUSI

VENTILASI : - HIPOKSEMIA- GAGAL JANTUNG

- BERIKAN O2 WALAUPUN PaO2 NORMAL

- DENGAN NASAL KANUL/ MASK 4 - 6 L/ MENIT

- HATI - HATI DGN PPOM (CO RETENSI)- KK PERLU DIPOMPA BILA

HIPOVENTILASI- ANALISA GAS BELUM PERLU - HINDARI PERDARAHAN - PULSE OXIMETRI +

PERANAN NITROGLISERIN DAN MORPHIN 1. SUBLINGUAL NTG (TEKANAN

DARAH SIST > 90 mm Hg 2. BILA BERLANJUT (EKG, AP) SBP <

90 mm Hg SUBLNGUAL + IV LINES (3 TABLET DLM 10 MENIT)

- MgSO4 --> AP 1 - 3 mg IV DLM 1 - 5 MENIT DAPAT

DIULANGI SAMPAI AP ANALGETIK +

MO : 1. RESISTENSI VENA --> VP --> PRELOAD

2. RESISTANSI ARTERI SISTEMIK --> AFTERLOAD

KEDUANYA MENGURANGI KERJAMIOKARD --> KEBUTUHAN O2

KATEKOLAMIN --> HIPOTENSI DENGAN HR --> PERLU CAIRAN IV

BILA BRADIKARDIA --> SA 1/2 - 1 mgBILA VOLUME DIKOREKSI

NTG TERLALU BANYAK --> MABP --> GANGGUAN TEKANAN PERFUSI KORONER --> TAKIKARDIA

RV INFARK SERING MENIMBULKAN HIPOTENSI --> NTG+

PENATALAKSANAAN ARITMIA I. PVC & IRAMA VENTRIKULER :

1. PVC 6 X / > PER MENIT 2. PVC YG BERUNTUN (QR / QT < 0,85)3. PVC DENGAN R ON T 4. PVC YG COUPLETS > 3X BERTURUT - TURUT (VT)5. PVC MULTIFORM

- LIDOCAINE SEBELUM TROMBOLITIK & BLOKADE BETA

- BLOKADE BETA : VF -, SSA, MENURUNKAN HR

- HIPOMAGNESIA DAN HIPOKALEMIA :

- IRAMA VENTR : - SEBELUM DI URETIKA KATEKOLAMIN

- 9 - 25 % HIPOKALEMIA --> VF - 49 % HIPOKALEMIA --> KARDIAK

ARREST

- DIKOREKSI DENGAN KCL 10 ME/ 100CC D5W/ 60 MENIT, DIULANGI TIAP JAM SAMPAI NORMOKALEMIA

MAGNESIUM - HIPOMAGNESEMIA SERING

BERSAMAAN DENGAN HIPPOKALEMIA --> REFRAKTER VF.

- 1 - 2 gr Mg SULFAT (2-3 ml LARUTAN 50% DL 100ml D5W)DLM 1 JM

- TIDAK MENURUNKAN MORTALITAS

II. BRADIKARDIA : HR < 60 X /MENIT

- GANGGUAN SSA --> PARASIMPATIS + --> BRADIKARDIA + --> JUNCTIONAL R 2 - 3 ND AV BLOK- BER DGN INFERIOR & POSTERIOR MI- HR < 60 X --> + HIPOTENSI/ IVR DIOBATI DGN SA 0,5 - 1 mg IV- HR < 50 --> SA : TPM : PPM

AIVR HRS DIOBATI - RIPERFUSI TERGANGGU, MENEKAN

DADA, BATUK - BATUK - PERLU SA - PREHOSPITAL :

- SA- EXT P.M

- ISOPROTERENOL 2 - 10 mg/ mnt --> PPM

SINUS TAKIKARDIA- HR > 100 X - IMA --> GJ :

- HIPOVOLEMIA- DEMAM, PERIKARDITIS,

ANEMIA, INFEKSO- BILA NYERI --> ANALGITIK /

SEDATIVA- ANTERIOR IMA PADA ORG MUDA ST - TERAPI : BLOK BETA 1,

CARDIOSELEKTIF

S.V ARITMIA - EVEK ADRENERGIK- IMA ANTERIOR- SINCRONISE DC UTK SINTOMATIK- ADENOSIN, VERAPHAMIL.,

DILTIAZEM (ALGORITMA)- KONTRA INDIKASI HIPOTENSI, LVF

ATRIOVENTRICULAR JUNCTIONAL RYTME :

- LVF, RVF- PACEMAKER PADA QRS MELEBAR

VT :- SEGERA DIATASI - LIDOCAINE ( STABIL, ASIMTIMATIK )- THUMB- DC

A-V BLOCK :- MOBITZ TIPE 2 --> PM - DERAJAT 3 --> PPM

INTRAVENTRIKULER BLOK :- RBBB + LA/ LPFB ~ MI ANTERIOR

--> - PPM

VF :- PALING BERBAHAYA & FATAL- VF + MI --> DC (ALGORITMA)- VF SEKUNDER (ISKEMIA,

HIPOTENSI, GJ --> 75 - 85 % MENINGGAL - DIPERLUKAN O2, VASODILATOR,

IABCP, PTCA, CABG

PENATALAKSANAAN TEKANAN DARAH IMA :

I. HIPOTENSI :- ALGORITMA - HIPOTENSI + MI -->PTCA

II. HIPERTENSI- O2 - ANTI ANX ANALGETIK- NTG IV (GJ +)- BLOKADE BETA (GJ -)- JAM - JAM PERTAMA --> BLOKADE BETA SELEKTIF- ANTI HT

IMA + GJ :4 KLASIFIKASI MENURUT KILLYP &

KIMBALLI. TANPA GJII. BENDUNGAN +III. UDEMA PARUIV. SYOK

INFARK VENT KANAN : - INVERIOR IMA 30%- HIPOTENSI, DISTENDED VENA

LEHER & PARU BERSIH- TERAPI : CAIRAN, DOBUTAMIN

SEBAB - SEBAB LAIN KEGAGALAN HEMODINAMIK

PADA IMA :1. EMBOLI PARU MASIF 2. HIPOVOLEMIK & SYOK SEPTIK3. TAMPONADE JANTUNG4. AORTIK DISSEKSION

PERTIMBANGAN TERAPI KHUSUS :1. BLOKADE BETA 2. NITROGLISERIN3. BLOKADE CA4. ASPIRIT, HEPARIN 5. TERAPI TROMBOLITIK

PERTIMBANGAN PADA PENDERITA DENGAN NYERI

DADA :- NYERI MUNGKIN DARI JANTUNG - UMUR LEBIH DARI 30 TH - SBP < 150 mmHg- DBP < 110 mmHg- LAMA NYERI DADA > DR 15 MENIT- GANGGUAN SEREBROVASKULER/

SUSUNAN SYARAF PUSAT > 6 BLN- TDK ADA PEMBEDAHAN/ TRAUMA

DLM 2 MNG- MASALAH PERDARAHAN - TDK ADA KEHAMILAN

KEY POINT

• THROMBOSIS• ANTI-COAGULANT

NEW TERMINOLOGY IN ACS

ACS, acute coronary syndrome; MI, myocardial infarction; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention.Cannon CP. J Thromb Thrombolysis. 1995;2:205-218.

AntithromboticTherapy

Stable Angina

UnstableAngina

Non–Q-wave MI

ThrombolysisPrimary PCI

Q-wave MI

Minutes-hours

Days-weeks

STEMIUA/NSTEMIAtherothrombosisNew term

Old term

PlaqueRupture

PLATELETACTIVATION &AGGREGATION

PLATELETACTIVATION &AGGREGATION

ATHEROSCLEROSISATHEROSCLEROSIS

PLAQUE RUPTUREPLAQUE RUPTUREDYSFUNCTIONAL

ENDOTHELIUMDYSFUNCTIONAL

ENDOTHELIUM

Intraplaquehemorrhage

Intraplaquehemorrhage

Release of Tissue Factor

Release of Tissue Factor

Exposure ofsubendothelial

collagen

Exposure ofsubendothelial

collagen

Turbulentblood flow

Turbulentblood flow

Vasodilatoreffect

Vasodilatoreffect

Anti thrombotic effect Anti thrombotic effect

CORONARY THROMBOSISCORONARY THROMBOSIS

VasoconstrictionVasoconstriction Vessel

umendiameter

Vessel umen

diameter

Activation ofthe coagulation

cascade

Activation ofthe coagulation

cascade

MECHANISMS OF CORONARY THROMBUS FORMATION

Presentation(Clinical, Initial ECG)

ST-Seg ElevationMyocardial Infarction

Non-STSeg ElevationAcute Coronary SyndrNon-STSeg ElevationAcute Coronary Syndr

ST-Seg ElevationMCI

Non-ST-seg-Elevation MCI

UnstableAngina

Workingdiagnosis

Time

Evolution ofECG &

Biomarkers

Finaldiagnosis

National Heart Foundation Australia &The Cardiac Society of Australia and New Zealand, MJA 2006

Atherogenesis and Atherothrombosis: A Progressive Process

NormalFatty

StreakFibrousPlaque

Athero-scleroticPlaque

PlaqueRupture/Fissure &

Thrombosis

Myocardial Infarction

Ischemic Stroke

Critical Leg

IschemiaClinically Silent

Cardiovascular Death

Increasing Age

AnginaTransient Ischemic Attack

Claudication/PAD

3

Lipid core

Adventitia

Thrombus

Unstable coronaryartery disease

Thrombus forms and extends into the lumenThrombus forms and extends into the lumen

RISK FACTORS FOR PLAQUE RUPTURE

Impaired Fibrinolysis

FibrinogenDiabetesMellitus

Cholesterol

SmokingCap Fatigue

Atheromatous Core(size/consistency)

Cap Inflammation

Systemic FactorsLocal Factors

Homocysteine

PlaqueRupture

Fuster V, et al. N Engl J Med. 1992;326:310-318.Falk E, et al. Circulation. 1995:92:657-671.

Cap Thickness/

Consistency

OUTCOMES OF PLAQUE DISRUPTION

1. Complete resolution and healing withlittle or no symptoms

(small thrombus)

2. Plaque growth and expansion causingNew onset or deteriorating angina

(partially occlusive thrombus)

3. Acute coronary thrombosis and occlusionleading to an Acute Coronary Syndrome

(Occlusive thrombus)

Pathway to Thrombosis

SLOW FLOW : VENOUS CIRCULATION

Fibrin PlateletsRBCs

Red Thrombus

CONSEQUENCES OF CORONARY THROMBUSCORONARY THROMBUSCORONARY THROMBUS

Small thrombus(non-flow limiting)

Small thrombus(non-flow limiting)

Partially occlusivethrombus

Partially occlusivethrombus

Occlusive thrombusOcclusive thrombus

No ECGchangesNo ECGchanges

ST segmentDepression and/orT wave inversion

ST segmentDepression and/orT wave inversion

ST elevation(Q wave later)

ST elevation(Q wave later)

Healing andPlaque enlargement

Healing andPlaque enlargement

UNSTABLE ANGINA

UNSTABLE ANGINA

NON-ST SEGEMENTELEVATION

NON-ST SEGEMENTELEVATION

ST SEGMENTELEVATIONST SEGMENTELEVATION

Negative Serum biomarkers

Transient ischemia Prolonged

ischemia

Positive Serum biomarkers

Positive Serum biomarkers

Four catagories of treatment :

1. Anti-ischaemic agents# Betablockers# Nitrate# Ca antagonist

2. Anti-platelet agents# Aspirin# Ticlopidine# Clopidogrel# GP IIa/IIIb inhibitor

3. Anti-thrombine / Anti-coagulant agents# Unfractionated heparin (UFH)# Low Molecular Weight Heparin (LMWH)# Fondaparinux# Bivalirudin

4. Coronary revascularization

Thienopyridine

TREATMENT OPTIONS

ACUTE CORONARY THROMBOSIS IN ACS

Plaque Rupture or Erosion

Platelet Activation

Platelet Activation

Adhesion/Aggregation

Adhesion/Aggregation

Platelet-RichThrombus

Platelet-RichThrombus

Coagulation Cascade

Coagulation Cascade

Fibrin Formation

Fibrin Formation

ASAASA

TiclopidineClopidogrel

TiclopidineClopidogrel

GlycoproteinIIb/IIIa

Inhibitors

GlycoproteinIIb/IIIa

Inhibitors

HeparinLow molecular weight heparin

HeparinLow molecular weight heparin

Direct ThrombinInhibitors

Direct ThrombinInhibitors

ThrombolyticThrombolytic

The New Paradigm in Anti-thrombotic therapy in ACS

Antiplatelet and anti-thrombotic therapyAntiplatelet and anti-thrombotic therapy

Reduce Thrombotic EventsReduce Thrombotic Events Minimize bleeding riskMinimize bleeding risk

Reduce MortalityReduce Mortality

Faktor IXFaktor IX

Faktor IXa Faktor VIIaFaktor VIIIa Faktor JaringanFosfolipid FosfolipidKalsium Kalsium

Faktor X Faktor X

Faktor XaFaktor VaFosfolipid Kalsium

Protrombin Trombin (faktor IIa)

Aktivasi plateletPembentukan fibrinAktivasi protein CAktivasi faktor V, VIII dan XIII

i

ii

i Inhibisi pembentukan trombin

ii Inhibisi aktivitas trombin

MEKANISME KERJA LOW MOLECULAR WEIGHT HEPARIN

COMPARISON OF UFH VS LMWH (2)

UFH LMWH UFH LMWH

Anti-Xa: Anti-IIa Activity ratio

Inhibit Activated thrombin

Inhibit thrombin production

Bioavailability

Requires Monitoring of APTT

Neutralized by Platelet Factor 4

1 : 1 3 : 1

Yes Yes

+ +++

Low High

Yes No

Yes No

Low-Molecular-Weight Heparin (LMWH)Low-Molecular-Weight Heparin (LMWH)

Fraction of standard (UFH) heparin Advantages over UFH:

– Greater bioavailability– No need to closely monitor– Resistant to inhibition by activated platelets– Lower incidence of HIT– Enhanced anti-factor Xa activity

Effective subcutaneous administration Fondaparinux, Enoxaparin, dalteparin,

reviparin, nadroparin, fraxiparin, parnafarin, others

Differ in anti-Xa/anti-IIa ratios

ANTICOAGULANTS INDIRECT THROMBIN INHIBITORS

Major Bleeding is Associated with an Increased Risk of Hospital Death in ACS Patients

Moscucci et al. Eur Heart J 2003;24:1815-23

GRACE Registry in 24,045 ACS patients

*After adjustment for comorbidities, clinical presentation, and hospital therapies**p<0.001 for differences in unadjusted death rates

OR (95% CI) 1.64 (1.18 to 2.28)*

0

Overall ACS UA NSTEMI STEMI

10

20

30

40

**

** **

**

5.1

18.6

3.0

16.1

5.3

15.3

7.0

22.8

Inh

os

pit

al d

ea

th (

%)

Inhospital major bleeding Yes

No

IIa II

Fibrinogen Fibrin clot

Extrinsic pathway

Intrinsicpathway

AT XaAT AT

Fondaparinux

Xa

Antithrombin

Fondaparinux: A Synthetic Factor Xa Inhibitor

Adapted with permission from Turpie AGG et al. N Engl J Med. 2001;344:619.

THROMBIN

20,000 patients with NSTE ACS

2 of 3: Age>60, ST Δ, positive cardiac markers

20,000 patients with NSTE ACS

2 of 3: Age>60, ST Δ, positive cardiac markers

Fondaparinux2.5 mg OD

Fondaparinux2.5 mg OD

MICHELANGELO: OASIS-5

ASA, Clopidogrel, IV GP IIb/IIIa as per local practiceASA, Clopidogrel, IV GP IIb/IIIa as per local practice

RandomizeRandomize

Enoxaparin1 mg/kg BIDEnoxaparin1 mg/kg BID

•Primary: Efficacy: Death, MI, refractory ischemia 9 day

Safety: Major bleeds

Risk benefit: Death, MI, refractory ischemia, major bleeds

•Secondary: Above & each component (especially deaths) at 30 & 180 d• Hypothesis: First test non-inferiority, then test superiority

•Primary: Efficacy: Death, MI, refractory ischemia 9 day

Safety: Major bleeds

Risk benefit: Death, MI, refractory ischemia, major bleeds

•Secondary: Above & each component (especially deaths) at 30 & 180 d• Hypothesis: First test non-inferiority, then test superiority

Outcomes

Efficacy Outcomes at Day 30Enox Fonda

Death/MI/RI 8.8% 8.1%

Death/MI 6.9% 6.2%

Death 3.5% 2.9%

MI 4.2% 3.9%

RI 2.3% 2.2%

Strokes

Death/MI/Stroke

P=0.022

P=0.077

0.8 1 1.2

P=0.031

Efficacy Outcomes at 6 Months

0.8 1 1.2

Enox Fonda

Death/MI/RI 13.1% 12.1%

Death/MI 11.2% 10.3%

Death 6.3% 5.6%

MI 6.3% 6.0%

Strokes 1.6% 1.3%

Death/MI/Stroke 12.3% 11.1%

P=0.055

P=0.036

P=0.037

P=0.33

P=0.029

P=0.005

Conclusions1. Fondaparinux is similar to enoxaparin in

reducing the risk of ischemic events at nine days.

2. Bleeding increases the risk of death significantly.

3. At one month and at 6 months there is a significant reduction in mortality with fondaparinux.

4. Strokes are also significantly reduced by fondaparinux, so that there is a clear reduction in death, MI, and strokes

5. Consistent results are observed in those undergoing PCI (including early PCI) and in every other subgroup examined.

Clinical Implications Treating 1000 ACS patients with fondaparinux instead of enoxaparin prevents:

- 10 deaths or MI- 4 strokes- 25 major bleeds

THE OASIS 5 TRIAL CLEARLY DEMONSTRATES THAT FONDAPARINUX IS THE PREFERRED

ANTICOAGULANT FOR TREATMENT OF ACS.