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3/3/2016
1
Acute Coronary Syndromes
(ACS)
Liane Horiuchi, Pharm.D.
PGY-1 Pharmacy Resident
Memorial Hospital Miramar
March 13, 2016
www.fshp.org
Disclosures
• Nothing to disclose concerning possible financial or
personal relationships with commercial entities that
may have a direct or indirect interest in the subject of
this presentation
2
Objectives
• Pharmacist:
– Distinguish between unstable angina (UA), non-ST
elevation myocardial infarction (NSTEMI) and ST-
segment elevation myocardial infarction (STEMI)
– Review treatment modalities in ACS
– Describe different reperfusion therapies and their roles
• Technician:
– Define ACS and its associated risk factors
– Review what drugs are used to treat ACS
– Explain the significance of timely treatment of ACS
3
Acute Coronary Syndrome (ACS)
• Definition: Clinical syndromes compatible with acute
myocardial ischemia and/or infarction due to an abrupt
reduction in coronary blood flow.
4
UAUA
NSTEMINSTEMISTEMISTEMI
3/3/2016
2
Risk Factors
Non-Modifiable
• Age
• Gender
• Ethnicity
• Family history
Modifiable
• Hypertension
• Hyperlipidemia
• Diabetes mellitus
• Smoking
• Overweight/Obesity
• Physical inactivity
5
Coronary Artery Disease
• Average age at first MI is 65 years for men and 71.8 years for
women.
• Each year, 635,000 Americans suffer a new coronary event,
and ~300,000 will suffer a recurrent attack.
• Approximately every 43 seconds, an American will have an
MI.
• Causes 1 out of every 7 deaths in the U.S.
Heart Disease and Stroke Statistics – 2015 Update. Circulation 2015.6
Diagnosis
Combination of Combination of Diagnostic Criteria
4 Differential Diagnosis
Non-CardiacChronic Stable
AnginaPossible ACS Definite ACS
NSTE
(NSTEMI/UA)STEMI
7NSTE: Non-ST-Segment Elevation
ACS Pathophysiology and Characteristics
Finks SW. Acute Coronary Syndromes. ACCP Updates in Therapeutics 2015.8
3/3/2016
3
Goals of Therapy
• UA/NSTEMI goals
– Prevent total occlusion
• Antiplatelets (ASA, P2Y12, +/- GPIs) + antithrombotic
– Control chest pain and associated symptoms
• STEMI goals
– Restore patency
• Door-to-needle < 30 min (Fibrinolytics)
• Door-to-balloon < 90 min (PCI)
• If >120 min to PCI, fibrinolysis unless CI
– Prevent complications
– Control chest pain and associated symptoms
9
Initial Management of NSTE-ACS
(UA/NSTEMI)
Immediate Management
• 12 Lead ECG (done by EMS & ED)
• History & Physical Examination
1. Nature of the anginal symptoms
2. Prior history of CAD
3. Sex (Male)
4. Older age (Most important in CHD)
5. Increasing number of traditional risk factors
• Cardiac Biomarkers (Troponin)
• TIMI and GRACE risk scores
11
Echocardiogram (ECG)
• EMS & w/in 10 min at ED, then q15-30min if not initially diagnostic
• ST-changes developing at rest strongly suggest acute ischemia:
ST ↑↑↑↑= STEMI ST ↓↓↓↓= NSTEMI ↔↔↔↔ = UA (?)
• Inverted T waves may also indicate UA/NSTEMI
• Q waves suggesting prior MI indicate a high likelihood of CAD
• ST elevation in posterior leads V7-V9 qualifies the patient for
reperfusion therapy as a STEMI
Normal ECG ≠ no NSTEMI or UA
12
3/3/2016
4
Timing of Release of Biomarkers After
Acute Myocardial Infarction
Anderson JL, et al. J Am Coll Cardiol 2007.
13
-Serial cardiac troponins at presentation
and 3-6 hours after symptom onset
Risk Assessment Tools
• TIMI: Thrombolysis in Myocardial Infarction
– Percent risk of all-cause mortality at 14 days in NSTE-ACS and at 30
days in STEMI-ACS
– Risk score determined by sum of presence of 7 variables at admission
(1 point each)
• GRACE: Global Registry of Acute Coronary Events
– Predicts in-hospital and 6 month mortality across ACS patients
14
TIMI Risk Assessment for NSTE-ACS
Antman EM. JAMA 2000. 15
*CAD risk factors: HTN, hyperlipidemia, DM, smoker, family hx of early MI
GRACE Risk Assessment
Amsterdam EA, et al. AHA/ACC guideline for the management NSTEMI ACS. Circulation 2014.16
3/3/2016
5
TIMI Risk Assessment for STEMI
Morrow DA. Circulation 2000. 17
Deciding between Early Invasive vs.
Conservative Strategies
Definitive/Likely ACS
Initiate ASA, BB, Nitrates,
Anticoagulants, Telemetry
Early Invasive Strategy
• TIMI Risk Score >3
•GRACE>140
• New ST segment depression
• Positive biomarkers
•High risk features
Ischemia Driven Strategy
•TIMI Risk Score 0-1 (Esp. Women)
•GRACE<109
•No ST segment deviation
•Negative Biomarkers
Coronary angiography
(24-48 hours)
Recurrent Signs/Symptoms
Heart failure
Arrhythmias
Remains Stable
↓
Assess EF and/or Stress Testing
↓
EF<40% OR Positive stress
Go to Angiography
Adapted from Moezzi SA, Acute Coronary Syndrome. 18
AHA/ACC Guideline Classification of
Recommendations and Level of Evidence
AHA/ACC Guideline for the management NSTEMI ACS. Circulation 2014.
19
Management of ACS
Anti-ischemic
Therapy
Oxygen
Nitroglycerin
β-blocker
Morphine
Antiplatelet
Therapy
Aspirin
P2Y12
inhibitor
GP IIb/IIIainhibitor
Anticoagulant
Therapy
UFH
Enoxaparin
Fondaparinux
Bivalirudin
Disease
modifying
therapy
Statin
ACE inhibitor
20
3/3/2016
6
Initial Management of ACS:
MONA + β-blockerDose Comments
Morphine 1-5mg IV q5min if sx not
relieved by NTG or recur
Oxygen If SaO2<90% or high-risk
features or hypoxia
Nitroglycerin (NTG)
CI: Sildenafil/ vardenafil
(w/in 24h), tadalafil (w/in
48h)
0.4mg spray or SL q5min x ≤3
doses
Call 911 if unresponsive to 1st dose
5-10mcg/min IV; titrate to CP
relief or 200mcg/min
-Used in first 48h for tx of persistent CP, HF
-Avoid if SBP<90mmHg or ≥30mmHg
below baseline
Aspirin (ASA) Chew and swallow non-enteric
coated 162-325mg x 1
-Reduces mortality
-Clopidogrel: If ASA allergy or GI
intolerance
Beta-blocker PO/IV initiated within 24 hours if
eligible
-Oral preferred
-Reduces mortality
-Avoid if signs of HF, ↑ risk of cardiogenic
shock, or CI
21
Lüscher TF, et al. European Heart Journal. August 2011. 22
Management of NSTE-ACS: Dual
Antiplatelet Therapy (DAPT)
Loading Dose Maintenance Dose COR LOE
Aspirin 162-325mg non-enteric coated 81-162mg daily I A
P2y12
inhibitors
Loading Dose
(PO)
Maintenance
Dose (PO)
Comments COR LOE
Clopidogrel
(Plavix)
300mg
(ischemia guided)
600mg
(PCI)
75mg daily Best if patient cannot drink full
class of water
I B
Ticagrelor*
(Brilinta)
180mg 90mg BID CI: ICH, severe hepatic disease I B
Prasugrel
(Effient)
60mg 10mg daily Option for PCI w/stenting; avoid
in Hx of TIA or stroke, >75y, or
<60kg
IIa B
AHA/ACC Guideline for the management NSTEMI ACS. Circulation 2014.23
*Reasonable to use in preference to clopidogrel in NSTE-ACS. (IIa, B)
*Recommended maintenance dose of aspirin is 81 mg daily.
DAPT for at least 12 months
PGY12 Antagonists
Adapted from Finks SW. Acute Coronary Syndromes. ACCP Updates in Therapeutics 2015. 24
Parameter Clopidogrel Prasugrel Ticagrelor
FDA Indication ACS managed medically or PCI ACS PCI ACS managed medically or PCI
Peak Platelet
Inhibition
LD: 300mg, ~6h,
600mg, ~2h
LD: 60mg, ~1-1.5h LD: 180mg, <1h
Adverse Effects Bleeding, GI hemorrhage Bleeding, HTN, HLD, A.fib,
bradyarrhythmia
Bleeding, ↑Scr, dyspnea
Metabolism Prodrug; 2-step process
involving 2C19 and 3A4
Prodrug; converted to active
metabolite via P450 pathways
Not prodrug; reversible
noncompetitive binding. 3A4
(primary), 3A5, Pgp
T1/28h metabolite 3.7h metabolite (2-15h range) 7h (parent), 9h(active metabolite)
Non-responders CYP2C19, CYP3A4 and Pgp
polymorphisms or interactions
No known issues No known issues
Drug/Disease
Interactions
PPIs inhibit 2C19 Less prone Careful with asthma, bradycardia;
limit ASA <100mg
Clinical trials CREDO, CURE, PCI-CURE,
CLARITY, COMMIT
TRITON-TIMI 38 PLATO*
3/3/2016
7
Management of NSTE-ACS:
Anticoagulant
Loading Dose Maintenance Dose Comments COR LOE
Heparin 60 IU/kg IVB
over >1 min
(Max 4000 IU)
12 IU/kg/hr (max1000IU/hr)
x 48h or until PCI performed
aPTT goal: 50-75s I B
Enoxaparin
(Lovenox)
30mg IVB 1mg/kg SQ Q12h x 24-48h
CrCl<30: Q24h
Highest bleeding
risk of 4 agents
I A
Fondaparinux
(Arixtra) -
2.5mg SQ daily
CrCl<30: Avoid
Best for those
with high risk of
bleeds
I B
Bivalirudin
(Angiomax)
0.1mg/kg IVB 0.25mg/kg/hr IV
if planned invasive surgery
Only in early
invasive strategy
or hx of HIT
I B
AHA/ACC Guideline for the management NSTEMI ACS. Circulation 2014.25
Management of NSTE-ACS:
GP IIb/IIIa inhibitor
GP IIb/IIIa
inhibitor
Loading Dose Maintenance Dose Comments COR LOE
Eptifibatide
(Integrilin)
180mcg/kg IVB
over 1-2 min
(Max 22.6 mg)
2mcg/kg/min IV
infusion x 12-72h
(Max 15 mg/hr)
CrCl<50: 1 mcg/kg/min
(Max 7.5 mg/hr)
•Continue until
discharge, CABG
initiation, or 72h
•CrCl<10mL/min
• CI: dialysis pts
IIb B
Tirofiban
(Aggrastat)
25mcg/kg IVB 0.15mcg/kg/min for up
to 18h
CrCl<60: 0.075
mcg/kg/min
IIb B
AHA/ACC Guideline for the management NSTEMI ACS. Circulation 2014.26
• Intermediate/High risk: GP IIb/IIIa inhibitor may be considered as part of initial tx in
early invasive strategy.
Other Early Hospital Therapies
• Nitrates: Topical or Oral
• ACE-Inhibitors:– CHF, EF<40%, HTN, DM, stable CKD (ARB if intolerant)
• Aldosterone antagonist:– On ACE-I and β-blocker with EF<40%, Sx HF or DM and if
CrCl>30 ml/min and K<5.0 mEq/L
• Calcium Channel Blocker: – For ischemic symptoms when β-blocker not successful, CI, or
intolerant
• Statins: High-intensity
• Nonsteroidal anti-inflammatory drugs (NSAIDs):– (Except aspirin) Should not be initiated and should be discontinued
during hospitalization
27
Immediate Invasive Strategy
• <90 minutes from presentation
• Refractory angina
• S/sx of HF or new/worsening mitral regurgitation
• Hemodynamic/electrical instability
• Recurrent angina or ischemia despite intensive medication
treatment
• Severe VT or VF
• Severe comorbidities
28
3/3/2016
8
Initial Management of STEMI
STEMI Treatment:
Reperfusion Therapy
Percutaneous Coronary
Intervention (PCI) Pharmacologic:
Fibrinolytic
https://www.nghs.com/fullpanel/uploads/files/cardiac-cath-lab.jpg30
Percutaneous Coronary
Intervention (PCI)
• Balloon angioplasty alone
• Balloon angioplasty with stents
– Bare metal stents (BMS)
– Drug-eluting stent (DES)
• Anti-proliferative agents: Sacrolimus, Paclitaxel, Everolimus, Zotarolimus
http://www.ica.artguys.com/IMAGES/Percutaneous-Coronary-Intervention.jpg31
Management of STEMI:
Reperfusion Therapy
ACCF/AHA Guideline for the Management of STEMI. 2013.
32
Bold lines are preferred strategies.
DIDO= door-in-door-out
*Patients with cardiogenic shock or severe HF initially seen at non-PCI-capable hospital should be
transferred for cardiac catheterization and revascularization as soon as possible, irrespective of time
delay from MI onset (I, B)
3/3/2016
9
STEMI Management
• Reperfusion therapy for all eligible patients with STEMI with
symptom onset ≤ 12 hrs
– Reperfusion therapy options: Percutaneous Coronary Intervention
(PCI) or fibrinolytic therapy
– First line� Primary PCI
• PCI- capable hospital (90 min) vs. non-PCI capable hospital (120
min)
– Second line� Fibrinolytic therapy
• If time is > 120 min to get to PCI hospital
33
STEMI Management
• Reperfusion therapy reasonable for patients with STEMI
with symptom onset in prior 12-24 hours if:
– Clinical and/or ECG evidence of ongoing ischemia
– First line: Primary PCI
• PCI also first line if..
– STEMI + cardiogenic shock, acute severe HF, or CI to fibrinolytics
34
Management of STEMI:
DAPT with Primary PCI
Loading Dose Maintenance Dose COR LOE
Aspirin 162 – 325mg
prior to procedure
81 -325mg daily
Indefinitely (I,A)
I B (LD)
P2Y12
inhibitors
Loading Dose Maintenance Dose COR LOE
Clopidogrel 600mg 75mg daily I B
Prasugrel 60mg 10mg daily I B
Ticagrelor 180mg 90mg BID* I B
ACCF/AHA Guideline for the Management of STEMI. 2013. 35
*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.
Management of STEMI:
Anticoagulant with Primary PCIAnticoagulant Loading Dose Follow-Up Dose COR LOE
UFH
With GP IIb/IIIa antagonist
planned
50- to 70-U/kg IVB to
achieve therapeutic ACT‡
Supplemental doses to
target ACT
I C
With no GP IIb/IIIa
antagonist planned:
70- to 100-U/kg IVB to
achieve therapeutic ACT§
Supplemental doses to
target ACT
I C
Lovenox
(Enoxaparin)
If last dose <8h, none
If last dose >8h, 0.3mg/kg
IVB if last dose 8-12h
prior
I B
Bivalirudin
(Angiomax)
0.75mg/kg IVB 1.75mg/kg/h IV*,
discontinue at end of PCI
or continue up to 4h as
needed
I B
Fondaparinux
(Arixtra)
Not recommended as sole anticoagulant for primary
PCI
III B
‡ Recommended ACT with planned GP IIb/IIIa antagonist tx is 200-250s.
§ Recommended ACT with no planned GP IIb/IIIa antagonist tx is 250-300s (HemoTec device) or 300-350s (Hemochron device).
* Reduce infusion to 1mg/kg/h w/estimated CrCl <30.
36
3/3/2016
10
Management of STEMI undergoing
PCI: GP IIb/IIIa inhibitor
ACCF/AHA Guideline for the Management of STEMI. 2013. 37
Loading Dose Maintenance Dose COR LOE
Abciximab
(ReoPro)
0.25mg/kg IVB 0.125mcg/kg/min (max
10mcg/min) x 12h
IIa A
Tirofiban
(Aggrastat)
high bolus dose
25mcg/kg IVB
over 3 min 0.15mcg/kg/min* x 18-24h
IIa B
Eptifibatide
(Integrilin)
double bolus
180mcg/kg IVB x 2
(10 min apart)
2mcg/kg/min** 18-24h IIa B
*In patients with CrCl <30 mL/min, reduce infusion by 50%
**In patients with CrCl <50 mL/min, reduce infusion by 50%, avoid in HD
• Of uncertain benefit if pretreated with P2Y12.
Management of STEMI: Anticoagulant
with Fibrinolytic Therapy
Anticoagulant Loading Dose Maintenance Dose COR LOE
UFH 60U/kg IVB
(Max 4000 U)
12 U/kg/h
(Max 1000U/h)
-Obtain aPTT at 1.5-2x control
x 48h or until revascularization
I C
Enoxaparin ≤75y: 30mg IVB
>75y: omit bolus
≤75y: 1mg/kg SQ q12h
>75y: 0.75mg/kg SQ q12h
CrCl <30:1mg/kg SQ q24h
index hospitalization, up to 8d
or until revascularization
I A
Fondaparinux 2.5mg IVB 2.5mg SQ daily for index hosp
up to 8d or until
revascularization
CrCl <30: CI
I B
ACCF/AHA Guideline for the Management of STEMI. 2013. 38
Reperfusion choice: Fibrinolytic
Fibrinolytic Agent Dose Patency rate Side effects
Alteplase
(rt-PA, Activase)
15mg IVP, then 0.75 mg/kg over
30 min (max 50mg), then 0.5mg/kg
(max 35 mg) over next 60 min
(total dose ≤ 100 mg)
73-84% Stroke, ICH
Reteplase
(r-PA, Retavase)
10 units IV; repeat dose in 30 min 84% Reperfusion
arrhythmias,
anemia
Tenecteplase
(TNK-tPA, TNKase)
Single IV dose:
Weight < 60 kg: 30mg
Weight 60-69 kg: 35mg
Weight 70-79 kg: 40mg
Weight 80-89 kg: 45mg
Weight >90 kg: 50mg
85% Minor bleeding,
reperfusion
arrhythmias
ACCF/AHA Guideline for the Management of STEMI. 2013. 39
Reperfusion choice: Fibrinolytics
Adapted from ACCF/AHA Guideline for the Management of STEMI. 2013. 40
3/3/2016
11
STEMI: Reperfusion therapy routes
2. Fibrinolytic
therapy
1. PCI
(Recommended)
3. Fibrinolytic,
then PCI
Adapted from Calil M, Perrin D. Acute Coronary Syndromes. 41
STEMI: Reperfusion therapy routes
2. Fibrinolytic
therapy
1. PCI
(Recommended)
3. Fibrinolytic,
then PCI
Adapted from Calil M, Perrin D. Acute Coronary Syndromes. 42
1. Reperfusion choice: PCI
Timeline of Antithrombotic therapy
During PCI
STEMI
diagnosed
After PCI
Aspirin
indefinitely and
P2Y12 inhibitor x
1 year
Before PCI:
� ASA 162-325 mg LD
� P2Y12 Inhibitor LD (any of following)
1. Clopidogrel 600 mg
2. Prasugrel 60 mg
3. Ticagrelor 180 mg
LD of Antiplatelets:
Aspirin and P2Y12
Inhibitor
+/-
GP IIb/IIIa antagonist
Anticoagulants:
UFH +/- GP
IIb/IIIa antagonist
or
Bivalirudin
Before PCI
After PCI:
� ASA 81-325 mg daily
� P2Y12 Inhibitor (any of the
following)
1. Clopidogrel 75mg daily
2. Prasugrel 10 mg daily
3. Ticagrelor 90mg BID
During PCI:
� Refer to dosing table
Adapted from Calil M, Perrin D. Acute Coronary Syndromes. 43
STEMI: Reperfusion therapy routes
2. Fibrinolytic
therapy
1. PCI
3. Fibrinolytic,
then PCI
Adapted from Calil M, Perrin D. Acute Coronary Syndromes. 44
3/3/2016
12
2. Reperfusion choice: Fibrinolytic
Timeline of Antithrombotic therapy
With Fibrinolytic
STEMI
diagnosed
LD of Antiplatelets:
Aspirin and P2Y12
Inhibitor
Anticoagulants:
UFH or
Enoxaparin (IV
& SQ)
Fondaparinux
Before Fibrinolytic
Aspirin indefinitely
and
P2Y12 inhibitor x
14 days-1 year
Before fibrinolytic:
-ASA 162-325 mg LD
-Clopidogrel as only P2Y12 inhibitor
• Age ≤ 75 y: 300 mg LD
• Age > 75: No LD, give 75 mg
2. Enoxaparin:
-Age < 75y: 30 mg IV bolus, then 1 mg/kg SQ q12h
-Age > 75y: no bolus; 0.75 mg/kg SQ q12h
3. Fondaparinux:
2.5 mg IV, then 2.5 mg SQ daily in 24h
Duration for both: Up to 8 days, or until
revascularization
After Fibrinolytic
With Fibrinolytic:
1. UFH: 60 U/kg IV bolus, then 12 U/kg/hr
infusion adjusted for aPTT 1.5-2x control
(~50-70s for 48h or until revascularization)
After Fibrinolytic: See dosing tableAdapted from Calil M, Perrin D. Acute Coronary Syndromes.
45
STEMI: Reperfusion therapy routes
2. Fibrinolytic
therapy
1. PCI
3. Fibrinolytic,
then PCI
Adapted from Calil M, Perrin D. Acute Coronary Syndromes. 46
PCI after fibrinolytic therapy
COR LOE
Immediate transfer for cardiogenic shock or severe acute HF
irrespective of delay from MI onset
I B
Urgent transfer for failed reperfusion or reocclusion IIa B
As part of invasive strategy in stable* patients with PCI between
3-24h after successful fibrinolysis
IIa B
*absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or sx supraventricular
tachyarrhythmias, and spontaneous recurrent ischemia
ACCF/AHA Guideline for the Management of STEMI. 2013. 47
With PCI
3. Reperfusion Choice: PCI after
fibrinolytic therapy
Timeline of Antithrombotic therapy
STEMI
diagnosed
LD of aspirin and
P2Y12 Inhibitor if did
not receive one before
Anticoagulants:
Continue UFH
or
Continue
Enoxaparin (IV)
Before PCI After PCI
Aspirin indefinitely and
P2Y12 inhibitor x 1 year
(DES) or for 30 days – 1
year (BMS)
Before PCI:
-If PCI ≤ 24h after fibrinolytic
therapy: Clopidogrel 300 mg LD
-If PCI > 24h after fibrinolytic
therapy: Clopidogrel 600 mg LD or
Prasugrel 60 mg
With PCI:
Enoxaparin
-If last dose ≤ 8h, no additional
drug
-If last dose > 8h, give 0.3 mg/kg
IV bolus
After PCI:
- Clopidogrel as maintenance
P2Y12 inhibitor
Adapted from Calil M, Perrin D. Acute Coronary Syndromes. 48
3/3/2016
13
Coronary Artery Bypass Graft (CABG)
• Limited role
• Indications:
– STEMI w/coronary anatomy not amenable to PCI + ongoing
ischemia, cardiogenic shock, severe HF
– STEMI at time of operative repair of mechanical defects
49
Coronary Artery Bypass Graft (CABG)
• Anti-thrombotic therapy:
� Give aspirin before CABG surgery
� Discontinue clopidogrel or ticagrelor ≥ 24h before “on-
pump” CABG
� Discontinue short acting IV GP IIb/IIIa antagonists ≥ 2-4h
before urgent CABG
� Discontinue abciximab ≥ 12h before urgent CABG
50
Late Hospital/Post-hospital Care
• Anti-ischemia Management
– Nitroglycerin
– Statins: High intensity if no CI
– Beta Blockers
– ACE inhibitors
– Aldosterone antagonists
• Oral Antiplatelet Therapy
– Aspirin
– P2Y12 inhibitor + ASA x ≥ 12 months
• Clopidogrel
• Ticagrelor
• Prasugrel (option for BMS or DES)
51
References
1. Amsterdam EA, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-
elevation acute coronary syndromes. Circulation. 2014.
2. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157.
3. Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.
4. Bruhl, SR. Acute Coronary Syndrome. Internal Medicine Didactics. July 2010.
5. Calil M, Perrin D. Acute Coronary Syndromes. Overview of ACCF/AHA Guidelines for Acute
Management of UA/Non-ST-Elevation Myocardial Infarction (NSTEMI) and ST-Elevation
Myocardial Infarction (STEMI).
6. Finks SW. Acute Coronary Syndromes. Cardiology I. ACCP Updates in Therapeutics 2015.
7. Lüscher TF et al. ESC Guidelines for the management of acute coronary syndromes in patients
presenting without persistent ST-segment elevation. European Heart Journal. August 2011.
8. O’Gara PT et al. ACCF/AHA Guideline for the Management of STEMI: A Report of the American
College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J
Am Coll Cardio. 2013; 61(4):e78-e140.
9. Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic
Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York:
Informa Healthcare USA, 2007:773–80.
10. TIMI Calculator: Morrow DA. Circulation 2000. Antman EM. JAMA 2000.
11. https://www.thrombosisadviser.com/static/media/images/upload/anticoagulants-and-antiplatelets-
target.jpg
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