Update Management Of

Acute Coronary Syndrome

In Clinical Practice
Novi Kurnianingsih

Update Management Of
Acute Coronary Syndrome
In Clinical Practice
Novi Kurnianingsih

CARDIOVASCULAR CONTINUUM

Major Risk Factor Atherosclerosis Disease

Controllable

Uncontrollable

Smoking

Male sex

High LDL and low HDL

Older age

Uncontrolled hypertension
Physical inactivity

Family history of
heart disease

Obesity

Post-menopausal

Uncontrolled diabetes

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY

Diagnosis of Acute MI
STEMI / NSTEMI
At least 2 of the following
Ischemic symptoms
Diagnostic ECG changes
Serum cardiac marker
elevations

Classification of Chest Pain

Typical angina
1. Steady retrosternal component
2. Provoked by exertion or stress
3. Relieved by rest or NTG

Atypical angina
. 2 of 3 criteria

Non-anginal chest pain

. 1 of 3 criteria
Am J Cardiol. 2010 Jun 1;105(11):1561-4

Clinical Presentation
Unstable Angina
Prolonged (>20 min) anginal pain at rest;
New onset (de novo ) angina (CCS Class II or III)
Recent destabilization of previously stable angina
with at least CCS Class III angina characteristics
(crescendo angina)
Post-MI angina

ECG Diagnosis
STEMI

NSTEMI

O'Connor R E et al. Circulation. 2010;122:S787-S817

Copyright American Heart Association, Inc. All rights reserved.

O'Connor R E et al. Circulation. 2010;122:S787-S817

O'Connor R E et al. Circulation. 2010;122:S787-S817

Copyright American Heart Association, Inc. All rights reserved.

Prehospital Fibrinolytic Checklist.

O'Connor R E et al. Circulation. 2010;122:S787-S817

Copyright American Heart Association, Inc. All rights reserved.

PERCUTANEOUS CORONARY
INTERVENTION (PCI)

CARDIAC CATHETERIZATION

Therapeutic Options in Acute

Coronary Syndromes
Anti-ischemic treatment
Antiplatelet agents
Anticoagulants
Revascularization/Reperfusion/Thrombolysi
s
Long term treatment/secondary prevention

European Heart Journal (2011) 32 , 29993054

LMWH ?
WHICH ONE ?

UFH ?

The New Paradigm

in Anti-thrombotic therapy in ACS
Antiplatelet
Antiplatelet and
and anti-thrombotic
anti-thrombotic therapy
therapy

Reduce
Reduce Thrombotic
Thrombotic Events
Events

Minimize
Minimize bleeding
bleeding risk
risk

Reduce
Reduce Mortality
Mortality

OASIS-6
JAMA. 2006;295:1519-1530

Randomized, double-blinded, controlled trial

comparing fondaparinux (2.5mg sc daily) to usual
care (either placebo, or UFH)
N = 12 092
Inclusion:
STEMI within 24h* onset of symptoms (shortened
to 12h after 4300 pts)
Exclusion:
Contraindications to anticoagulation (including
high bleeding risk)
Renal failure

OASIS-6
JAMA. 2006;295:1519-1530

Primary End point: death/reinfarction at 30d

Fondaparinux vs UFH, death/reinfarction in patients undergoing primary

PCI

OASIS 6 Trial: Primary Endpoint

Reduction in Death/MI: Stratum 1
(No UFH indicated)

Reduction in Death/MI: Stratum 2

(UFH Indicated)

p<0.05

p=NS

p=0.97

The reduction in the primary endpoint at 30 days in the Fondaparinux group

was driven by Stratum 1, where death/MI occurred less frequently among Fonda
pts than Placebo (11.2 vs. 14%, HR 0.79, p<0.05)
There was no difference in Stratum 2, comparing those patients who received
Fondaparinux vs those who received UFH (8.3% vs. 8.7%, HR 0.96, p=NS)
Presented
Presented at
at ACC
ACC 2006
2006

OASIS 6 Trial: Primary Composite Endpoint

Components of Primary Composite Endpoint (%) Among the
components of the
p=0.03
composite at 30
days, mortality was
lower in the
fondaparinux group
compared to the
control group (7.8%
p=0.06
vs. 8.9%, HR 0.87,
p=0.03).
Reinfarction was
also lower in the
fondaparinux group
compared to the
control group (2.5%
vs. 3.0% HR 0.81,
p=0.06).
Presented
Presented at
at ACC
ACC 2006
2006

OASIS-5: Fondaparinux in UA/NSTEMI

N Engl J Med 2006;354:1464-76

Fondaparinux Group

Other standard treatments as per investigators discretion

Fondaparinux could be given up to hospital d/c or 8d

Enoxaparin was continued 2-8d (until patient was deemed stable)
* Enoxaparin dosing was q24h if GFR was less than 30 mL/min

OASIS-5 efficacy and safety at

day 9
Death, MI, refractory ischaemia

Major bleeding

Fondaparinux

0.05

Cumulative hazard

Cumulative hazard

Enoxaparin

0.04

0.06

Enoxaparin

0.04

HR 1.01
95% CI 0.90, 1.13

0.03
0.02
0.01
0.00

HR 0.52
95% CI 0.44, 0.61
p<0.001

0.03

0.02

Fondaparinux

0.01

0.00
0

Days

Days

Primary efficacy endpoint: 5.8% (fondaparinux) vs 5.7%

(enoxaparin)
Major bleeding: 2.2% (fondaparinux) vs 4.1% (enoxaparin)
OASIS-5 Trial Group NEJM 2006. Available at www.nejm.org

OASIS-5: Fondaparinux in UA/NSTEMI

N Engl J Med 2006;354:1464-76

AHS Current Recommendations

Dont give fondaparinux to:
1. STEMI patients going directly to PCI
2. Patients with Renal failure (GFR <30
mL/min or Cr <265mmol/L)
3. Patients going directly to the cath lab
Fondaparinux can generally be used for all
other cases of ACS as 2.5mg SC daily

Fondaparinux:
Targeted Mechanism of Action
Intrinsic
pathway

Extrinsic
pathway

Antithrombin
AT

AT

AT

Xa

Xa

Fondaparinux

II

Fibrinogen
Turpie AGG et al. N Engl J Med. 2001;344:619.

IIa

Fibrin clot

Pharmacologic comparison
Pharmacotherapy 23(6):772-787, 2003

Property

UFH

LMWH

Fondaparinux

Source

animal

animal

synthetic

T1/2

~3h

~4h (variable)

17-21h

Bioavailability
(SC)

30%

>90%

100%

Elimination

Reticuloendothelial
and renal

renal

renal

Induced HIT*

2-5%

1-2%

Not observed

Inter or intrapatient
variability

+++

++

Monitoring

aPTT
Plt count

Plt count

nil

Reversal

Protamine

Protamine

FFP

* Discussed later

THANK YOU

CONTOH KASUS #1
Seorang wanita usia 65 tahun datang ke UGD dengan
keluhan nyeri dada kiri dirasakan sejak 3 jam yll, saat sedang
mengangkat benda berat, terasa berat menjalar ke lengan
dan bahu kiri dengan durasi lebih dari 30 mnt, disertai
keringat dingin , pasien mempunyai riwayat hipertensi dan
kolesterol tidak terkontrol
TD: 150/80 HR :100 x/mnt, RR 20X/min, Sat 02 95%
Cor dan pulmo dbn
Akral hangat

ECG

CONTOH KASUS #2
Seorang pria usia 56 tahun datang ke UGD dengan
keluhan nyeri dada kiri sejak 4 jam yll terasa ampeg
menjalar ke lengan kiri disertai keringat dingin dan
mual ,pasien merupakan perokok aktif dan
mempunyai riwayat darah tinggi tidak terkontrol
Pemeriksaan Fisik:
TD: 80/50 mmHg, HR 50 x/mnt reguler, Sat 02
95%, RR 20 x/mnt
JVP meningkat, Ronkhi (-), akral dingin, nadi
lemah

ECG

CONTOH KASUS #3
Pasien laki laki usia 49 tahun datang ke UGD dengan sesak
hebat tiba tiba diawali dengan dada ampeg, baru pertama
kali seperti ini, riwayat diabetes tidak terkontrol
Pemeriksaan Fisik
Pasien tampak sesak hebat dan gelisah
TD 190/100 mmHg ; HR 130 x/mnt, RR 40 x/mnt, Sat 02
85%
JVP meningkat, Gallop +, RBH seluruh lapangan paru
Akral hangat

ECG