Principle Management

of
Acute Coronary Syndrome

Nahar Taufiq
Bagian Kardiologi dan Kedokteran Vaskuler FK UGM
Yogyakarta
 Atherothrombosis* is the
Leading Cause of Death Worldwide1

Pulmonary Disease 6.3

Injuries 9

AIDS 9.7

Cancer 12.6

Infectious Disease 19.3

Atherothrombosis* 22.3

0 5 10 15 20 25 30
Causes of Mortality (%)

*Atherothrombosis defined as ischemic heart disease and cerebrovascular disease.

1
The World Health Report 2001. Geneva: WHO; 2001.
Reprod.with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.
 Atherothrombosis: A Generalized and
Progressive Disease
Atherothrombosis

Unstable
angina ACS
MI
Ischemic
stroke/TIA
Atherosclerosis Critical leg
ischemia
Intermittent
claudication
CV death

Stable angina/Intermittent claudication

MI = Myocardial infarction
ACS = Acute coronary syndromes
Adapted from Libby P. Circulation 2001; 104: 365–372
CV = Cardiovascular
 Thrombus Formation and ACS
Plaque Disruption/Fissure/Erosion

Thrombus Formation

Old
Terminology: UAP NQMI STE-MI

New UAP Non-ST-Segment ST-Segment

Terminology: Elevation Elevation
Acute Coronary Acute
Syndrome (NSTE-ACS) Coronary
Syndrome
(STE-ACS)
 Pathophysiology

Ruptured Plaque with Occlusive Thrombus Formation

UAP or STEMI-ACS
NON STEMI-ACS
 Initial Recognition
in the Emergency Department
 P Ex ED Evaluation of Patients

Brief Physical Examination in the ED

1. Airway, Breathing, Circulation (ABC)
2. Vital signs, general observation
3. Presence or absence of jugular venous distension
4. Pulmonary auscultation for rales
5. Cardiac auscultation for murmurs and gallops
6. Presence or absence of stroke
7. Presence or absence of pulses
8. Presence or absence of systemic hypoperfusion (cool,
clammy, pale, ashen)
P Ex ED Evaluation of Patients

Differential Diagnosis of STEMI: Life-Threatening

Aortic dissection Tension pneumothorax

Pulmonary Emboli Boerhaave syndrome
Perforating ulcer (esophageal rupture with
mediastinitis)
 P Ex ED Evaluation of Patients

Differential Diagnosis of STEMI:

Other Cardiovascular and Nonischemic

Pericarditis LV hypertrophy with

Atypical angina strain
Early repolarization Brugada syndrome
Wolff-Parkinson-White
syndrome Myocarditis
Deeply inverted T- Hyperkalemia
waves suggestive of a Bundle-branch blocks
central nervous
system lesion or Vasospastic angina
apical hypertrophic Hypertrophic
cardiomyopathy cardiomyopathy
P Ex ED Evaluation of Patients

Differential Diagnosis of STEMI: Other Noncardiac

Gastroesophageal Cervical disc or

reflux (GERD) and neuropathic pain
spasm Biliary or pancreatic pain
Chest-wall pain Somatization and
Pleurisy psychogenic pain
Peptic ulcer disease disorder

Panic attack
 Dx Electrocardiogram

I IIa IIb III If the initial ECG is not diagnostic of STEMI,

serial ECGs or continuous ST-segment
monitoring should be performed in the patient
who remains symptomatic or if there is high
clinical suspicion for STEMI.
 Dx Electrocardiogram

I IIa IIb III Show 12-lead ECG results to emergency

physician within 10 minutes of ED arrival in all
patients with chest discomfort (or anginal
equivalent) or other symptoms of STEMI.

I IIa IIb III In patients with inferior STEMI, ECG leads

should also be obtained to screen for right
ventricular infarction.
 Dx Laboratory Examinations

I IIa IIb III Laboratory examinations should be performed as part

of the management of STEMI patients, but should not
delay the implementation of reperfusion therapy.

 Serum biomarkers for cardiac damage

 Complete blood count (CBC) with platelets
 International normalized ratio (INR)
 Activated partial thromboplastin time (aPTT)
 Electrolytes and magnesium
 Blood urea nitrogen (BUN)
 Creatinine
 Glucose
 Complete lipid profile
 Dx Biomarkers of Cardiac Damage

I IIa IIb III Cardiac-specific troponins should be used as

the optimum biomarkers for the evaluation of
patients with STEMI who have coexistent
skeletal muscle injury.

I IIa IIb III For patients with ST elevation on the 12-lead

ECG and symptoms of STEMI, reperfusion
therapy should be initiated as soon as
possible and is not contingent on a biomarker
assay.
 Initial Management
in the Emergency Department
 Tx Oxygen

I IIa IIb III

Supplemental oxygen should be administered to
patients with arterial oxygen desaturation (SaO2
< 90%).

I IIa IIb III

It is reasonable to administer supplemental
oxygen to all patients with uncomplicated STEMI
during the first 6 hours.
 Nitroglycerin
Tx

I IIa IIb III Patients with ongoing ischemic discomfort

should receive sublingual NTG (0.4 mg) every 5
minutes for a total of 3 doses, after which an
assessment should be made about the need for
intravenous NTG.

I IIa IIb III

Intravenous NTG is indicated for relief of ongoing

ischemic discomfort that responds to nitrate
therapy, control of hypertension, or management
of pulmonary congestion.
 Tx Nitroglycerin

I IIa IIb III

Nitrates should not be administered to patients
with:
• systolic pressure < 90 mm Hg or ≥ to 30 mm Hg
below baseline
• severe bradycardia (< 50 bpm)
• tachycardia (> 100 bpm) or
• suspected RV infarction.
I IIa IIb III

Nitrates should not be administered to patients

who have received a phosphodiesterase
inhibitor for erectile dysfunction within the last
24 hours (48 hours for tadalafil).
 Tx Analgesia

Morphine sulfate (2 to 4 mg intravenously

I IIa IIb III
with increments of 2 to 8 mg intravenously
repeated at 5 to 15 minute intervals) is the
analgesic of choice for management of pain
associated with STEMI.
 Tx Aspirin

I IIa IIb III

Aspirin should be chewed by patients who

have not taken aspirin before presentation
I IIa IIb III
with STEMI. The initial dose should be 162
mg (Level of Evidence: A) to 325 mg (Level of
Evidence: C)

Although some trials have used enteric-coated aspirin

for initial dosing, more rapid buccal absorption occurs
with non–enteric-coated formulations.
 Tx Clopidogrel
CLARITY-TIMI 28
15
Placebo
20%
End point* (%)

10 Clopidogrel

5
P=0.03

0
0 5 10 20 25 30

Days
* Cardiovascular death, recurrent MI, or recurrent ischemia leading to
the need for urgent revascularization

Sabatine MS et al for the CLARITY-TIMI 28 Investigators. N Engl J Med 2005;352:1179-89

CLARITY-TIMI 28: Tingkat keamanan dalam 30 hari

ASA + CLO
ASA P=0.24
4

P=0.80 3.4
P=0.12
3 2.7
% of patients

2
1.9
1.7 1.6

1
0.9

0
Major bleeding Minor bleeding Major or minor
bleeding
Tx Onset of antiplatelet
Agent Dose Onset

Aspirin Dosis 80 - 320 mg1 15 - 30 minutes

Clopidogrel 75 mg maintenance dose2 Max at 3-7 days

300 mg loading dose3 Max at 24 to 48 h

600 mg loading dose4 Max at 2 h

900 mg loading same with 600 mg loading

dose3 dose

Ticlopidine 250 mg 2x perhari5 50% pada 5 hari dan

maksimum 8-11 hari

1 Dabaghi SF et al. Am J Cardiol 1994;74:720-3. 2. Savcic M et al. Semin Thromb Hemost 1999;25:15-19

3 Quinn MJ, Fitzgerald DJ. Circulation 1999;100:1667-72 4. Hochholzer W et al. Circulation

2005;111:2560-4 5. Lubbe DF, Berger PB. J Interv Cardiol

 Initial Management in the ED

Mona_C
o

1 2 3
1
Reperfusion Therapy and
Recommendations
STEMI
Tx Reperfusion

The medical system goal is to facilitate rapid

recognition and treatment of patients with STEMI

such that door-to- needle (or medical contact–to-

needle) time for initiation of fibrinolytic therapy

can be achieved within 30 minutes or that door-

to-balloon (or medical contact–to- balloon) time for

PCI can be kept within 90 minutes.

 Treatment Delayed is Treatment Denied

Symptom Call to PreHospital ED-Hospital Cath Lab

Recognition Medical System

Increasing Loss of Myocytes

Delay in Initiation of Reperfusion Therapy

 Reperfusion Options for STEMI Patients
Select Reperfusion Treatment.
If presentation is < 3 hours and there is no delay to an invasive
strategy, there is no preference for either strategy.

Fibrinolysis generally preferred

 Early presentation ( ≤ 3 hours from symptom
onset and delay to invasive strategy)
 Invasive strategy not an option
 Cath lab occupied or not available
 Vascular access difficulties
 No access to skilled PCI lab

 Delay to invasive strategy

 Prolonged transport
 Door-to-balloon more than 90 minutes
 > 1 hour vs fibrinolysis (fibrin-specific agent) now
 Contraindications and Cautions
for Fibrinolysis in STEMI

Absolute • Any prior intracranial hemorrhage

Contraindications • Known structural cerebral vascular lesion
(e.g., arteriovenous malformation)
• Known malignant intracranial neoplasm
(primary or metastatic)
• Ischemic stroke within 3 months EXCEPT
acute ischemic stroke within 3 hours
NOTE: Age restriction for fibrinolysis has been removed
compared with prior guidelines.
 Contraindications and Cautions
for Fibrinolysis in STEMI

Absolute • Suspected aortic dissection

Contraindications
• Active bleeding or bleeding diathesis
(excluding menses)
• Significant closed-head or facial trauma
within 3 months
 Contraindications and Cautions
for Fibrinolysis in STEMI
Relative • History of chronic, severe, poorly controlled
Contraindications hypertension
• Severe uncontrolled hypertension on
presentation (SBP > 180 mm Hg or DBP >
110 mm Hg)
• History of prior ischemic stroke greater than
3 months, dementia, or known intracranial
pathology not covered in contraindications
• Traumatic or prolonged (> 10 minutes) CPR
or major surgery (< 3 weeks)
 Contraindications and Cautions
for Fibrinolysis in STEMI

Relative • Recent (< 2 to 4 weeks) internal bleeding

Contraindications • Noncompressible vascular punctures
• For streptokinase/anistreplase: prior
exposure (> 5 days ago) or prior allergic
reaction to these agents
• Pregnancy
• Active peptic ulcer
• Current use of anticoagulants: the higher the
INR, the higher the risk of bleeding
 Reperfusion Options for STEMI Patients
Select Reperfusion Treatment.
If presentation is < 3 hours and there is no delay to an invasive strategy,
there is no preference for either strategy.

Invasive strategy generally preferred

 Skilled PCI lab available with surgical backup
 Door-to-balloon < 90 minutes

• High Risk from STEMI

 Cardiogenic shock, Killip class ≥ 3

 Contraindications to fibrinolysis, including

increased risk of bleeding and ICH

 Late presentation
 > 3 hours from symptom onset

 Diagnosis of STEMI is in doubt

2-3

Antithrombin Therapy
and Recommendations
Non-STEMI & UAP
 ACC/AHA Recommendations for
Antithrombin Therapy in Patients with
NSTE-ACS
• Class I
– Anticoagulation with subcutaneous LMWH or intravenous
UFH should be added to antiplatelet therapy
– Dose of UFH 60-70 U/kg (max 5000) IV followed by
infusion of 12-15 U/kg/hr (initial max 1000 U/hr) titrated
to aPTT 1.5-2.5 times control
– Dose of enoxaparin 1 mg/kg subcutaneously q12 hr; the
first dose may be preceded by a 30-mg IV bolus
– Fundaparinoux SC
• Class IIa
– Enoxaparin is preferable to UFH as an anticoagulant
unless CABG is planned within 24 hours

Available at: www.acc.org/clinical/guidelines/unstable/unstable.pdf.

1 2 3
 Secondary Prevention
and
Long Term Management
Secondary Prevention and Long Term Management

Goals Recommendations

Smoking • Assess tobacco use.

Goal:
Complete • Strongly encourage patient and family
Cessation to stop smoking and to avoid secondhand
smoke.

• Provide counseling, pharmacological

therapy (including nicotine replacement
and bupropion), and formal smoking
cessation programs as appropriate.
Secondary Prevention and Long Term Management
Goals Recommendations
If blood pressure is 120/80 mm Hg or greater:
Blood pressure
control:
• Initiate lifestyle modification (weight control,
Goal: < 140/90
physical activity, alcohol moderation, moderate
mm Hg or
sodium restriction, and emphasis on fruits,
<130/80 mm
vegetables, and low-fat dairy products) in all
Hg if chronic
patients.
kidney disease
or diabetes
If blood pressure is 140/90 mm Hg or greater or
130/80 mm Hg or greater for individuals with
chronic kidney disease or diabetes:

• Add blood pressure-reducing medications,

emphasizing the use of beta-blockers and inhibitors
of the renin-angiotensin-aldosterone system.
Secondary Prevention and Long Term Management

Goals Recommendations

Physical • Assess risk, preferably with exercise test, to

activity: guide prescription.
Minimum goal:
30 minutes 3 to
4 days per • Encourage minimum of 30 to 60 minutes of
week; activity, preferably daily but at least 3 or 4 times
Optimal daily weekly (walking, jogging, cycling, or other aerobic
activity) supplemented by an increase in daily
lifestyle activities (e.g., walking breaks at work,
gardening, household work).

• Cardiac rehabilitation programs are

recommended for patients with STEMI.
Secondary Prevention and Long Term Management
Goals Recommendations
Lipid • Start dietary therapy in all patients (< 7% of total
management: calories as saturated fat and < 200 mg/d
(TG less than cholesterol). Promote physical activity and weight
200 mg/dL) management. Encourage increased consumption of
Primary goal: omega-3 fatty acids.
LDL-C << than
100 mg/dL • Assess fasting lipid profile in all patients,
preferably within 24 hours of STEMI. Add drug
therapy according to the following guide:

LDL-C < 100 mg/dL (baseline or on

treatment):
Statins should be used to lower LDL-C.

LDL-C ≥ 100 mg/dL (baseline or on

treatment):
Intensify LDL-C–lowering therapy with drug
treatment, giving preference to statins.
Secondary Prevention and Long Term Management
Goals Recommendations
Lipid If TGs are ≥ 150 mg/dL or HDL-C is < 40 mg/dL:
management: Emphasize weight management and physical
(TG 200 mg/dL activity. Advise smoking cessation.
or greater)
Primary goal: If TG is 200 to 499 mg/dL:
Non–HDL-C << After LDL-C–lowering therapy, consider adding
130 mg/dL fibrate or niacin.

If TG is ≥ 500 mg/dL:
Consider fibrate or niacin before LDL-C–lowering
therapy.
Consider omega-3 fatty acids as adjunct for high
TG.
 NCEP ATP III Guidelines
Initiate TLC* Drug therapy LDL
Patients with if LDL considered if LDL treatment
goal

0 1 risk factors 160 mg/dL†  190 mg/dL <160 mg/dL†

(160 –189 mg/dL:
drug optional)

10 year risk 10–

2 risk factors 130 mg/dL† 20%:  130 mg/dL <130 mg/dL†
(10 year risk 20%) 10-year risk <10%:
 160 mg/dL

CHD and CHD risk  130 mg/dL

equivalents 100 mg/dL† (100–129 mg/dL: <100 mg/dL†
(10 year risk >20%) drug optional)

†
100 mg/dL = 2.6 mmol/L; 130 mg/dL = 3.4 mmol/L; 160 mg/dL = 4.1 mmol/L

National Cholesterol Education Program, Adult Treatment Panel III. JAMA 2001;285:2486–2497
* TLC: therapeutic lifestyle changes
Secondary Prevention and Long Term Management
Goals Recommendations

Weight
management: Calculate BMI and measure waist
Goal: circumference as part of evaluation. Monitor
BMI 18.5 to 24.9 response of BMI and waist circumference to
kg/m2 therapy.

Waist Start weight management and physical activity

circumference: as appropriate. Desirable BMI range is 18.5 to
Women: < 35 in. 24.9 kg/m2.
Men: < 40 in.
If waist circumference is ≥ 35 inches in women
or ≥ 40 inches in men, initiate lifestyle changes
and treatment strategies for metabolic
syndrome.
Secondary Prevention and Long Term Management

Goals Recommendations
Diabetes Appropriate hypoglycemic therapy to
management: achieve near-normal fasting plasma
Goal: glucose, as indicated by HbA1c.
HbA1c < 7%
Treatment of other risk factors (e.g.,
physical activity, weight management,
blood pressure, and cholesterol
management).
Guidelines for the Use of Enoxaparin in Patients
with NSTE-ACS

• 1 mg/kg SQ q12 hours (actual body weight)

– An initial 30 mg IV dose can be considered
• Adjust dosing if CrCl <30 cc/min
– 1 mg/kg SQ q24 hours
• Do not follow PTT; do not adjust based on PTT
• Stop if platelets  by 50% or below 100,000/mm3
• If patient to undergo PCI:
– 0-8 hours since last SQ dose: no additional antithrombin therapy
– 8-12 hours since last SQ dose: 0.3 mg/kg IV immediately prior to
PCI
 Applying Classification of
Recommendations and Level of Evidence
Class I Class IIa Class IIb Class III

Benefit >>> Risk Benefit >> Risk Benefit ≥ Risk Risk ≥ Benefit
Additional studies with Additional studies with No additional studies
focused objectives broad objectives needed; needed
needed Additional registry data
would be helpful Procedure/Treatment
Procedure/ Treatment IT IS REASONABLE to should NOT be
SHOULD be perform Procedure/Treatment performed/administered
performed/ procedure/administer MAY BE CONSIDERED SINCE IT IS NOT
administered treatment HELPFUL AND MAY BE
HARMFUL

should is reasonable may/might be considered is not recommended

is recommended can be useful/effective/ may/might be reasonable is not indicated
is indicated beneficial usefulness/effectiveness is should not
is useful/effective/ is probably recommended or unknown /unclear/uncertain is not
beneficial indicated or not well established useful/effective/beneficial
may be harmful
 Applying Classification of
Recommendations and Level of Evidence

Level A Class I Class IIa Class IIb Class III

Multiple (3-5) • Recommen- • Recommen- • Recommen- • Recommen-

population risk dation that dation in favor dation’s dation that
strata evaluated procedure or of treatment or usefulness/ procedure or
treatment is procedure efficacy less treatment not
General useful/ being useful/ well useful/effective
consistency of effective effective established and may be
direction and • Sufficient • Some • Greater harmful
magnitude of evidence from conflicting conflicting • Sufficient
effect multiple evidence from evidence from evidence from
randomized multiple multiple multiple
trials or meta- randomized randomized randomized
analyses trials or meta- trials or meta- trials or meta-
analyses analyses analyses
 Applying Classification of
Recommendations and Level of Evidence

Level B Class I Class IIa Class IIb Class III

Limited (2-3) • Recommen- • Recommen- • Recommen- • Recommen-

population risk dation that dation in favor dation’s dation that
strata evaluated procedure or of treatment or usefulness/ procedure or
treatment is procedure efficacy less treatment not
useful/effective being useful/ well established useful/effective
• Limited effective • Greater and may be
evidence from • Some conflicting harmful
single conflicting evidence from • Limited
randomized evidence from single evidence from
trial or non- single randomized trial single
randomized randomized or non- randomized trial
studies trial or non- randomized or non-
randomized studies randomized
studies studies
 Applying Classification of
Recommendations and Level of Evidence

Level C Class I Class IIa Class IIb Class III

Very limited (1- • Recommen- • Recommen- • Recommen- • Recommend-

2) population dation that dation in favor dation’s ation that
risk strata procedure or of treatment or usefulness/ procedure or
evaluated treatment is procedure efficacy less treatment not
useful/ being well established useful/effective
effective useful/effective • Only diverging and may be
• Only expert • Only diverging expert opinion, harmful
opinion, case expert opinion, case studies, or • Only expert
studies, or case studies, or standard-of- opinion, case
standard-of- standard-of- care studies, or
care care standard-of-
care
Pathway to Thrombosis
 Tx Beta-Blockers

Oral beta-blocker therapy should be

I IIa IIb III
administered promptly to those patients without
a contraindication, irrespective of concomitant
fibrinolytic therapy or performance of primary
PCI.

I IIa IIb III

It is reasonable to administer intravenous beta-
blockers promptly to STEMI patients without
contraindications, especially if a tachyarrhythmia
or hypertension is present.
 Summary of Trials of Beta-Blocker Therapy

Phase of Total No. RR (95% CI)

Treatment Patients

Acute 28,970 0.87 (0.77-0.98)

treatment

Secondary 24,298 0.77 (0.70-0.84)

prevention

Overall 53,268 0.81 (0.75-0.87)

0.5 1 2
Relative risk (RR) of death
Beta blocker Placebo
better better

Antman E, Braunwald E. Acute Myocardial Infarction. In:

Braunwald E, Zipes DP, Libby P, eds. Heart Disease: A
textbook of Cardiovascular Medicine, 6th ed.,
Philadelphia, PA: W.B. Sanders, 2001, 1168.
 Comparison of Heparin + ASA vs ASA Alone
Theroux

RISC

Cohen 1990

ATACS

Holdright
Gurfinkel
Summary Relative Risk
0.67 (0.44-0.1.02)
0.1 1 10
Heparin + ASA RR: ASA Alone
55/698=7.9% Death/MI 68/655=10.4%

ASA indicates acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ATACS, Antithrombotic Therapy in Acute
Company Syndromes; RR, relative risk; and MI, myocardial infarction.
Data from Oler A, Whooley MA, Oler J, et al. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in
patients with unstable angina: a meta-analysis. JAMA. 1996;276:811-815. Slide reproduced with permission from Cannon CP.
Atherothrombosis slide compendium. Available at: www.theheart.org.
 ESSENCE Results
Tx
Unfractionated Heparin
30% Enoxaparin (Lovenox)

25%
Recurrent Angina
Death, MI or

20%
15%
P = 0.02
10%
Risk Reduction 16.2%
5%
0
5 9 13 17 21 25 29
Days After Randomization
Adapted with permission from Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight
heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous
Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997;337:447-452. Copyright © 1997,
Massachusetts Medical Society. All rights reserved.
 TIMI 11B: Enoxaparin vs.
Heparin in NSTE-ACS
20 Unfractionated Heparin
16.7 %
Urgent Revascularization

Enoxaparin (Lovenox)
16
Death, MI or

12 14.2 %

8
p = 0.03
4 Relative Risk Reduction = 15%

0 2 4 6 8 10 12 14
Days
Adapted from Antman EM, et al. Circulation. 1999;100:1593-1601.