1. ACUTE CORONARY SYNDROME
The newest management
Nahar Taufiq
Jogja International Hospital
Yogyakarta

2. 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.

3. 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

4. Pathway to Thrombosis

5. Thrombus Formation and ACS
Plaque Disruption/Fissure/Erosion
Thrombus Formation
Old
Terminology: UA NQMI STE-MI
New Non-ST-Segment Elevation ST-Segment
Terminology: Acute Coronary Syndrome (NSTE-ACS) Elevation
Acute
Coronary
Syndrome
(STE-ACS)

6. GUSTO IIb: Correlation of 6-Month Mortality
With Baseline ECG Findings in Patients With
ACS
10
ST ↓ ACS
Cumulative Mortality
8
STEMI with
6 fibrinolytics
(%)
4
T-wave
inversion
2
0
0 30 60 90 120 150 180
Days From Randomization
GUSTO indicates Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes; ECG, electrocardiogram;
ACS, acute coronary syndrome; and STEMI, ST-segment elevation myocardial infarction.
Figure adapted with permission from Savonitto S, Ardissino D, Granger CB, et al. Prognostic value of the admission
electrocardiogram in acute coronary syndromes. JAMA. 1999;281:707-713. Copyright © 1999, American Medical Association. All
rights reserved.
Slide reproduced with permission from Cannon CP. Atherothrombosis slide compendium. Available at: www.theheart.org.

7. Initial Recognition and
Management
in the Emergency Department

8. 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)

9. P Ex ED Evaluation of Patients
Differential Diagnosis of STEMI: Life-Threatening
Aortic dissection Tension pneumothorax
Pulmonary Boerhaave syndrome
embolus (esophageal rupture with
Perforating ulcer mediastinitis)

10. 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

11. 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
disorder
Peptic ulcer disease
Panic attack

12. 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.

13. 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.

14. 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

15. 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.

16. 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.

17. 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.

18. 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).

19. 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.

20. 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.

21. Tx Clopidogrel in Non STEMI
Cumulative events (myocardial infarction, stroke, or cardiovascular death)
Cumulative hazard rate
0.14 Placebo * (n =6,303)
20%
0.12
0.10
0.08 Clopidogrel * (n = 6,259)
0.06
p < 0.0001
0.04
0.02
0.00
0 3 6 9 12
Months of follow-up
*On top of standard therapy (including acetylsalicylic acid)
The CURE Trial Investigators. N Engl J Med 2001; 345: 494–502

22. Tx Clopidogrel in Non STEMI
1 0.9
Bleeding rate (%)
0.8 0.7
0.6
0.4
0.2
0.2 0.1
0
Fatal Intracranial Require surg Drop of Hb
interv > 5 g/dl
The CURE Investigators. N Engl J Med 2001;345:494-502

23. Tx Clopidogrel in Non STEMI
Primary endpoint ‡ ) during 24 hours
0.025
0.020 Placebo
Cumulative hazard
0.015
0.010
Clopidogrel
0.005 P=0.003
rates
0.0
0 2 4 6 8 10 12 14 16 18 20 22 24
Hours after randomization
‡ Cardiovascular death, myocardial infarction, stroke and severe ischemia
Yusuf S et al. Circulation 2003; 107: 966–972

24. Tx Clopidogrel in STEMI
Placebo (10.1%)
10
reinfarction or stroke before first
Proportion with death, 9
8 Clopidogrel (9.3%)
discharge (%)
7
6
RRR=9%
5
P=0.002
4
3
2
1
0
0 7 14 21 28
Time since randomization (days)
COMMIT= ClOpidogrel and Metoprolol in Myocardial Infarction Trial
COMMIT Collaborative Group. Lancet 2005;366:1607-21

25. CLARITY-TIMI 28: angka kejadian kumulative
dalam 30 hari
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

26. 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

27. 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

28. 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.

29. 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.

30. Tx
Reperfusion Therapy and
Recommendations
STEMI

31. 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.

32. Treatment Delayed is Treatment Denied
Symptom Call to PreHospital ED-JIH Cath Lab
Recognition Medical System
Increasing Loss of Myocytes
Delay in Initiation of Reperfusion Therapy

33. 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

34. 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

35. Tx
Antithrombin Therapy Studies
and Recommendations
NonSTEMI

36. 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.

37. 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.

38. 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.

39. 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
• 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.

40. Mona_C
o

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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.

49. 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

50. 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)

51. 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