ACS Lecture

Acute
Coronary
Syndromes
LIZA KOREN-SELFRIDGE, PHARM.D.
PHARMACY 544: PHARMACOTHERAPY
FEBRUARY 2, 2016
Objectives
Describe the pathophysiology of ACS including risk factors, plaque

development and progression to ACS
Understand the clinical signs and symptoms, lab values and EKG changes
associated with ACS
Given subjective and objective patient information, determine which form
of ACS the patient is experiencing (UA, NSTEMI, STEMI)
Describe various therapies used in acute and long term management for
ACS and understand their role in therapy:
MONA (morphine, oxygen, nitroglycerin, aspirin)
Antiplatelet/Anticoagulation
Glycoprotein Iib/IIIa inhibitors
Fibrinoloytics
Beta blockers
ACE-I/ARBs
Objectives
Compare and contrast diagnosis, goals of therapy and

treatment options for UA/NSTEMI and STEMI
Given a patient case, determine which form of ACS the
patient is experiencing and synthesize an appropriate
therapeutic treatment and monitoring plan
Describe the long-term complications associated with MI
and recommend appropriate long-term medication
therapy to reduce these complications and decrease
mortality
Epidemiology
Estimated 15.5 million Americans 20 years of

age have coronary heart disease (CHD)
By 2030, projections suggest prevalence will
increase by ~18% from 2013 estimates
An American will have a myocardial infarction
(MI) every 43 seconds
Heart Disease and Stroke Statistics 2015 Update. Circulation. 2015; 131:e29-e322
Epidemiology
Myocardial infarction
(MI) prevalence
Men = 4.0%
Women = 1.8 %
Age at first MI:
Men = 65 years
Women = 71.8 years
Epidemiology
Mortality rate in people who experience an MI 15%

1 year mortality post-MI
Women 45 years 26%
Men 45 years 19%
Heart Failure within 5 years of MI
45-64 years: 8% of men, 18% of women
65 years: 20% of men, 23% of women
From 1990 2006
Acute MI mortality declined from 10.4% to 6.3%
37% of NSTEMI mortality decline and 21% STEMI mortality decline
attributed to improvements in acute treatment
Definition: Acute Coronary Syndrome
(ACS)
Non-ST
Asymptomatic Unstable ST Elevation
Stable Angina Elevation MI
Atherosclerosis Angina MI (STEMI)
(NSTEMI)
Acute Coronary
Syndrome (ACS)
- Varying degrees of coronary artery
occlusion resulting in imbalance
between myocardial oxygen demand
Dipiro JT, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011
Pathophysiology: Acute Coronary
Syndromes
What differentiates ACS from chronic

coronary artery disease (CAD)?
Ischemia resulting from imbalance between oxygen demand and

oxygen supply to cardiac tissue
blood flow typically due to an occlusive or partially occlusive
atherothrombotic coronary plaque
CAD progression to Acute Coronary
Syndromes
Predominant cause of ACS is
rupture, fissuring or erosion of
unstable atherosclerotic plaque
Plaques occluding < 50% are less
stable (more likely to rupture)
Large, soft lipid core
Thin fibrous cap
High macrophage content
Leads to partially or completely
occlusive thrombus formation on
ruptured plaque
Complete occlusion STEMI
Partial occlusion UA/NSTEMI
Consequences of Plaque Rupture
Plaque Disruption/Rupture Activation of extrinsic

- Thrombogenic contents of plaque exposed to coagulation cascade
the blood
- Thrombin (factor IIa) production
- Converts fibrinogen fibrin
Platelet Adhesion to site of

injury
- Via platelet glycoprotein Ib (GP Ib)
to von Willebrand factor (VWF)
Fibrin Clot
Formation
Platelet Activation
- Synthesis/Release of
thromboxane A2 (TXA2), adenosine
diphosphate (ADP) Promotes conformational
change in GP IIb/IIIa
surface receptors
- Increases platelet cross- Platelet Clot
ADP binds P2Y1 and P2Y2 linking via increased Formation
receptors on platelets fibrinogen affinity
Amplification of
platelet aggregation
and recruitment
CAD progression to Acute Coronary
Syndromes
Diagnosis
History and Clinical Presentation

Electrocardiogram (ECG)
Laboratory Results
Cardiac Biomarkers
Risk Factors for ACS
Hypertension
Dyslipidemias
Diabetes mellitus
Age
Gender
Tobacco Use
Obesity
Familial/Genetics
Clinical Presentation
Substernal chest pain/pressure

May radiate to shoulder, jaw, back or down left arm
At rest, severe new-onset, increasing angina > 20 min in duration
Nausea/Vomiting
Diaphoresis
Shortness of Breath
Atypical presentation more common in women, elderly and DM
Without classic chest pain
Epigastric discomfort
Shortness of Breath
12-lead ECG should be performed within 10 minutes of

initial presentation
Key Findings which may indicate MI:
ST-segment elevation
ST-segment depression
T-wave inversion
New left bundle branch block
Non-ST Elevation MI
Unstable Angina (UA) Non-ST Elevation MI
(NSTEMI)
- ST-segment depression
- ST-segment depression (NSTEMI)
- Transient ST-segment
- Transient ST-segment - ST-segment elevation
elevation
- T-wave inversion elevation
- T-wave inversion
Absence of ECG findings does not automatically rule out

MI
Changes may be difficult to detect depending on location
Important to review findings in context with clinical
presentation and cardiac biomarkers
Lab Findings: Cardiac Biomarkers
Cardiac Biomarkers biochemical markers of

myocardial cell death
Increased levels in the blood indicate stress, damage and/or
necrosis of cardiac tissue
Creatine kinase MB (CK-MB)

Troponin-I Preferred - More
specific and sensitive
Troponin-T marker of myocardial
damage and necrosis
Longo DL, Fauci AS, Kasper DL et al. Harrisons Principles of Internal Medicine. 18 th ed. New York, NY: McGraw-Hill 2012
Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3 rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA,
2007:77380. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157, Figure 5.
Single measurement is not adequate

Cardiac biomarkers should be drawn at least twice,
typically 6 hours apart
Biomarker Rise Peak Persistence
CK-MB 3-6H 12-24H 2-3 days

(0-6%)
Troponin-T 2-6H 12-48H 10-14 days

variable
Troponin-I 2-6H 18-24H 5-7 days

variable
Postive cardiac biomarkers help to differentiate between

UA and NSTEMI
UA cardiac biomarkers negative
NSTEMI cardiac biomarkers positive
STEMI cardiac biomarkers positive
Degree of troponin elevation is directly related to severity
of heart tissue damage and mortality
Minor troponin elevations in patients with an unclear
history or presentation of MI may be due to other reasons
i.e. CHF, myocarditis, pulmonary embolism, demand ischemia
How do you differentiate between Acute
Coronary Syndromes?
Non-ST segment ST-segment

Unstable Angina
elevation MI elevation MI
(UA)
(NSTEMI) (STEMI)
Degree of artery
occlusion
ECG Findings
Cardiac
Biomarkers
General ACS Treatment Goals
Restore blood flow to artery/cardiac tissue

Prevent infarct expansion
Prevent complete occlusion
Prevent mortality and prevent/minimize MI
complications
Relieve chest pain, signs/symptoms of angina
Prevent coronary artery reocclusion with reinfarction
ACS Management Algorithm
OConner RE, Brady W, Brooks SC et al. Part 10: Acute Coronary Syndromes. Circulation 2010;122:S787-S817
Treatment of ACS
Initial Treatment of ACS

- MONA therapy
- HPI (symptoms, risk factors), ECG, labs (cardiac biomarkers) *UA/NSTEMI also
referred to as
NSTE-ACS
STEMI UA / NSTEMI*
- TIMI Risk Score
Antiplatelet, Anti-ischemic, Antiplatelet, Anti-ischemic,

anticoagulation therapy anticoagulation therapy
Thrombolyti Thrombolyti
PCI/CABG
cs cs
Long-term Medical Management

Patient Case - AD
AD is a 76 yo M who presents to the ER complaining of 10/10 chest pain. Pain started

~3 hours ago while sitting at home watching TV and is described as a dull, aching jaw
and chest pain.
PMH: HTN, DM, former smoker (1 ppd x 20 years) Allergies: PCN
FH: Father died of stroke (age 80)
SH: retired, lives alone, spends a lot of time watching TV
Medications:
- ASA 325 mg daily
- Lisinopril 5 mg daily
- Glyburide 5 mg daily
- Sildenafil 25 mg prn ED
Pre-Hospital/Early ER Care
Obtain IV access
Obtain ECG
Labs (cardiac biomarkers)
MONA therapy
Morphine
Oxygen
Nitroglycerin
Aspirin
MONA: Morphine
Treatment of chest pain not relieved by nitroglycerin

Dose: 1-5 mg IV every 5-30 minutes as needed
Therapeutic Effect:
Analgesic/Anxiolytic
Decreases myocardial O2 demand
Heart Rate
Venodilation
Monitoring:
Hypotension
Respiratory Depression
Confusion
MONA: Oxygen
For hypoxia and/or respiratory distress

Administer to patients w/oxygen saturation (O2 sat) <
90%
Benefit of routine oxygen supplementation to non-
hypoxic patients has not been demonstrated
2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes. Circulation. 2014; 130:e344-e426
MONA: Nitroglycerin
Treatment of chest pain

First line before morphine unless contraindicated
Dose:
0.4 mg sublingual every 5 min (x3 doses)
IV infusion (persistent symptoms)
5-10 mcg/min, titrated up to 75-100 mcg/min until symptoms
resolve
May continue up to 24-48 hours
Therapeutic Effect:
Coronary/Peripheral vasodilation
cardiac preload, BP, myocardial O2 demand
MONA: Nitroglycerin
Side Effects:
Hypotension
Headache
Flushing
Tachycardia
Nitrate Contraindications
SBP < 90 mmHg
Severe bradycardia (< 50 bpm) OR tachycardia (> 100 bpm)
Suspected RV infarction
Phosphodiesterase inhibitor administration
Sildenafil, vardenafil within last 24 hours
Tadalafil within last 48 hours
MONA: Aspirin (ASA)
Should be administered to all ACS patients as soon as

possible
Unless allergy, active bleeding or major GI intolerance
Rapid inhibition of thromboxane A2 (TXA2) platelet

inhibition
Mortality benefit - Reduces incidence of recurrent MI and
death
Dose: 162 325 mg, non-enteric coated should be chewed
ASA maintenance dose continued indefinitely
Alternative if ASA contraindicated: Clopidogrel

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation. 2013; 127
Early Beta-Blocker Administration
Initiate within first 24 hours (for all ACS patients without

contraindications)
Oral agents preferred over IV
Therapeutic Effect:
HR, contractility, arterial pressure myocardial O2 demand
Diastolic ventricular filling time coronary artery perfusion
Early administration reduces incidence of:

Recurrent Ischemia
Re-infarction
Ventricular arrhythmias
Long-term mortality
Agent Selection
Beta-1 selective agents preferred
Avoid beta-blockers with intrinsic sympathomimetic activity (ISA)
Beta-blocker Contraindications
HR < 60 bpm
Systolic BP < 90 mmHg
Signs of cardiogenic shock/hypo-perfusion
2nd or 3rd degree heart block
Signs of heart failure
COPD/asthma? (Relative not contraindicated in absence of active
bronchospasm)
Increased risk factors for cardiogenic shock*
Early Beta-Blocker Administration COMMIT
Trial
Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT)

Early IV metoprolol, followed by PO vs. Placebo in acute MI (STEMI and NSTEMI)
Results
1endpoint: composite death, reinfarction, cardiac arrest No difference between
groups
Lower rate of recurrent MI and arrhythmic death in metoprolol group
Increased rate of cardiogenic shock (especially within first 24 hours) in metoprolol
group
Risk was higher in certain subgroups: > 70 years, systolic BP < 120 mmHg, HR > 110 bpm,
increased time since onset of symptoms
Take Home: Consider later administration of beta blockers in

MI patients at higher risk of cardiogenic shock
COMMIT Collaborative group. Early intravenous then oral metoprolol in 45852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1622-32
Side Effects
Hypotension
Acute heart failure
Bradycardia
Heart Block
Early Renin-Angiotensin-Aldosterone
System Inhibitors
Should be administered within first 24 hours to the following

patients (Class I-A):
STEMI (anterior infarct)
HF (EF 40%)
Reasonable for all STEMI patients with no contraindications
(Class IIa-A)
ARB is acceptable alternative
Mortality benefit - Reduces fatal and nonfatal major CV events
in STEMI patients
Caution: hypotension, renal failure, hyperkalemia
Patient Case AD (continued)
Physical Exam:
- Vitals: BP 140/100, HR 100, RR 24, O2 sat 98% (on room air)
- Pale, diaphoretic, anxious
- Normal heart sounds
ECG: sinus tachy, ST segment depression
What
Chest XR: no apparent edema, normal heart size initial therapy
should AD receive?
Labs: CK-MB: 10 ng/mL (elevated)
Troponin: 0.7 ng/mL x 1 (elevated) What type of ACS is most
likely?
Whats next??
Treatment of ACS

- MONA therapy
- HPI (symptoms, risk factors), ECG, labs (cardiac biomarkers)
STEMI UA / NSTEMI
- TIMI Risk Score

Thrombolyti PCI/Cath PCI/Cath

cs Intervention Intervention

UA/NSTEMI Management
Two strategies for management of UA/NSTEMI:

1. Medical Management (aka Ischemia-Guided Strategy)
2. Percutaneous Coronary Intervention (PCI) w/ or w/out stent
placement (aka Early-Invasive Strategy)
How do we decide which strategy to

use?
Risk Stratification - What is the likelihood of an
adverse outcome based on patient specific risk factors?
Risk Stratification: VERY High Risk
Patients with the following clinical features are considered very

HIGH RISK:
Cardiogenic Shock
Overt heart failure, severe left ventricular dysfunction
Recurrent/persistent angina despite intensive medical therapy
Hemodynamic instability 2/2 mechanical complications
Unstable ventricular arrhythmias
Will typically proceed to PCI immediately no risk stratification
required
Risk stratification applied in the absence of immediate high risk
indicators
TIMI Risk Stratification
Thrombolysis in Myocardial Infarction (TIMI) Score

Calculates risk of mortality, new or recurrent MI, or severe recurrent
ischemia at 14 days TIMI All-Cause Mortality, New or Recurrent MI, or
Risk Factors Point Risk Severe Recurrent Ischemia Requiring Urgent
s Score Revascularization Through 14 Days After
Age 65 years 1 Randomization
3 risk factors for CAD: smoking, 1
diabetes, HTN, hyperlipidemia, family 0-1 4.7 %
history of CAD LOW
2 8.3 %
Prior history of CAD (>50% stenosis on 1
coronary angiography) 3 13.2 % INTERMEDIA
Aspirin use in past 7 days 1 4 19.9 % TE
2 anginal events in past 24 hours 1 5 26.2 % HIG
ST-segment deviation on ECG 1 H
6-7 40.9 %
Elevated cardiac biomarkers 1
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157, Table 8. TIMI = Thrombolysis in Myocardial Infarction.
NSTEMI Medical Management
For patients in BOTH the Early-Invasive and Ischemic-Guided Strategy

(aka ALL NSTEMI patients with definitive or likely UA/NSTEMI):
MONA
Antiplatelet Therapy
- Aspirin
- P2Y12 Inhibitor
- GP IIb/IIIa Receptor Inhibitors
Anticoagulation
- UFH
- LMWH
- Fondaparinux
- Bivalirudin
Antiplatelet Therapy P2Y12 Inhibitors
Recommended in addition to aspirin (Dual Antiplatelet Therapy,

DAPT) for all NSTE-ACS patients
Blocks ADP from binding P2Y12 receptors, resulting in
platelet aggregation
fibrinogen cross-linking
Available agents:
Clopidogrel
Prasugrel
Ticagrelor
Antiplatelet Therapy P2Y12 Inhibitors
Clopidogrel Ticagrelor Prasugrel

Indication ACS medical ACS medical ACS w/PCI
(NOT for DAPT in medical
management or w/PCI management or w/PCI management)
Dosing Load: 300-600 mg x1 Load: 180 mg x1 Load: 60 mg x1
Maintenance: 75 mg Maintenance: 90 mg BID Maintenance: 10 mg*
daily daily
(*5 mg if < 60 kg, 75
years)
Other Prodrug converted Not a prodrug Prodrug
to active form via More rapid onset than More rapid onset than
CYP2C19 clopidogrel clopidogrel
May be used as Reversible P2Y12 Contraindication:
alternative in ASA receptor binding active bleed, prior
intolerant patients ASA doses must be < stroke/TIA
Contraindication: 100 mg w/ticagrelor
ICH,
2014 AHA/ACC Guideline for the Management severe
of Patients hepatic
with Non-ST-Elevation Acute Coronary Syndromes. Circulation. 2014; 130:e344-e426
Antiplatelet Therapy GP IIb/IIIa Receptor
Inhibitors
Glycoprotein IIb/IIIa receptors are located on the platelet surface

Binding to receptor results in conformational change affinity to
fibrinogen
GP IIb/IIIa Receptor Inhibitors prevent binding
Decrease platelet aggregation and thrombus formation
May be considered in NSTEMI patients undergoing PCI,
w/intermediate/high risk features (i.e. positive troponin)
In addition to dual antiplatelet therapy
Preferred agents: eptifibatide, tirofiban
All agents should be used in combination with heparin (UFH or LMWH) or
ASA
Inhibitors
Abciximab Eptifibatide Tirofiban

PCI: 25 mcg/kg IV bolus;
PCI: 180 mcg/kg IV
then 0.15 mcg/kg/min x
PCI: 0.25mg/kg IV bolus; bolus x2 doses (10 min
18-24 hours
then 0.125mcg/kg/min x apart); then 2
ACS w/out PCI: 0.4
Dosing 12 hours mcg/kg/min x 18-24
mcg/kg/minute x 30
ACS w/out PCI: not hours
minutes; then 0.1
recommended ACS w/out PCI: same
mcg/kg/min x 18-72
as above (only 1 bolus)
hours
Half-life 30 min (unbound) 2.5 hours 2 hours
CrCl < 50 ml/min:
Renal Renal adjustment not CrCl < 30 ml/min:
reduce by 50%
Impairment necessary
Avoid in hemodialysis
reduce by 50%
Platelet fxn
Up to 15 days 4-8 hours 4-8 hours
returns in:
Inhibitors
Take Home Message for GP IIb/IIIa Receptor

Inhibitors:
Not used routinely in ACS w/out PCI
May be considered in NSTEMI w/PCI if
intermediate/high risk
If used:
Preferred agents: eptifibatide, tirofiban
Check renal function adjust accordingly
Should be used in conjunction with heparin (UFH or LMWH)
Anticoagulation
Recommended, in addition to anticoagulation therapy,

for patient with definite or likely NSTE-ACS
Anticoagulation Treatment Options:

For all NSTE-ACS Patients (w/ or w/out PCI)
Enoxaparin
Unfractionated heparin
Fondaparinux
For ONLY NSTE-ACS patients undergoing PCI

Bivalirudin
Anticoagulation Agent Comparison
Enoxaparin 1 mg/kg subcutaneous q12h

Low Molecular Weight Heparin (LMWH)
Duration: length of hospital stay, or until PCI
Requires renal dosing for CrCl < 30 ml/min
Unfractionated Heparin (UFH) 60 units/kg IV load (max 4000 units), initial

IV infusion 12 units/kg/hour (max 1000 units) adjusted per aPTT according
to hospital protocol
Duration: 48 hours or until PCI performed
No renal dosing required
Fondaparinux 2.5 mg subcutaneous daily

Factor Xa inhibitor
Duration: length of hospital stay or until PCI
Requires renal dosing for CrCl < 30 ml/min
Anticoagulation Agent Comparison
Bivalirudin 0.75 mg/kg IV load prior to PCI, 1.75 mg/kg/hr

infusion
Direct Thrombin Inhibitor (DTI)
Used in NSTE-ACS patients undergoing PCI
Not well studied in early conservative medical management
Duration: Continued until PCI
Monotherapy in PCI pts (ACUITY & HORIZON trial)

Bivalirudin alone non-inferior to UFH or Enoxaparin combined with GP
IIb/IIIa receptor inhibitor in preventing ischemic complications
major bleeds with Bivalirudin monotherapy
not recommended with GP IIb/IIIa inhibitor in most pts
NSTEMI Medical Management Summary
Ischemia Guided
Early Invasive (PCI)
(Medical Management) ASA
ASA +
+ P2Y12 Inhibitor (clopidogrel,
P2Y12 Inhibitor ticagrelor, prasugrel)
(clopidogrel, ticagreolor) +
+ Anticoagulant (Enoxaparin,
Anticoagulant UFH, Bivalirudin, Fondaparinux)
(Enoxaparin, UFH, +/-
Fondaparinux)
Glycoprotein IIa/IIIb inhibitor
(epitifibitide, tirofiban)
Percutaneous Coronary Intervention (PCI)
Who is eligible?
High risk unstable angina/Non-STEMI
Persistent symptoms
Recurrent ischemia
Depressed LV function
Widespread ECG changes
Prior AMI, PCI, CABG
High Risk-Score (i.e. TIMI)
Patients with STEMI

Primary Percutaneous Coronary
Intervention (PCI)
http://www.topofthesouthcardiology.co.nz/nelson-
angiography.html
http://www.nhlbi.nih.gov/health/health-
topics/topics/stents/placed
PCI w/Stent Placement
Pre-stent Post-stent
placement placement
catheter
Complete occlusion
wire probing
wire
1 2 3
stent culprit
stent blockage
deployed
blood flow
restored
4 5 6
Pre-stent Post-stent
placement placement
Types of Stents (BMS vs. DES)
Bare Metal Stents

Concern for smooth muscle
Drug Eluting Stents
(BMS)
proliferation re-stenosis (DES)
Coated with antiproliferative
Higher risk of early onset re-
medication* to inhibit/prevent
stenosis tissue growth
Lower cost Decreased need for
revascularization
Shorter required time period
for dual antiplatelet therapy Concern for late onset
(elective PCI) thrombosis
Possibly beneficial for patients
Requires longer period of dual
w/adherence issues or high
antiplatelet
* sirolimus, therapy
paclitaxel (electiveeverolimus
(1 gen) zotarolimus, PCI)
bleed risk
st
(2nd gen)
Bare Metal Stent (BMS) vs. Drug Eluting
Stent (DES)
BMS
(Day 0
and
Day
30)
BMS
vs.
DES
Patient Case AD (continued)
Based on his risk stratification, ECG and elevated

troponins, the MD has decided that he will go to
the cath lab for PCI and likely stent placement
- What pharmacologic regimen should AD be on

prior to his PCI?
Treatment of ACS

- MONA therapy
- HPI (symptoms, risk factors), ECG, labs (cardiac biomarkers) *UA/NSTEMI also
referred to as
NSTE-ACS
STEMI UA / NSTEMI*
- TIMI Risk Score

Thrombolyti PCI/Cath PCI/Cath

cs Intervention Intervention

STEMI Treatment Goal
Reperfusion therapy to rapidly re-establish coronary artery blood flow

Strategies for reperfusion
1. Cath Lab Intervention (Percutaneous Coronary Intervention, PCI) -
preferred
2. Fibrinolytics
Time = Muscle
Timeline for STEMI treatment
10
minutes
30
minutes
90
minutes
Prompt Thrombolytic Rx Cath Lab
assessmen Door to Needle Door to
t& Balloon
general
treatment
Reperfusion therapy should be
administered to all eligible patients with
STEMI with symptom onset within prior
Dipiro JT, Talbert RL, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach. 8 ed. New York, NY: McGraw-Hill;12
th
2011 hours (Class I-A)
Primary PCI vs. Fibrinolytics for STEMI
Primary PCI preferred over fibrinolytics when it can be performed

in a timely fashion
Lower mortality rate
PCI > 90% of occluded infarct-related coronary arteries opened
Compared to < 60% w/fibrinolytics
Reduced stroke/ICH, major bleeding risk
If patient cannot undergo PCI within 90 minutes of onset of
symptoms, fibrinolytic therapy should be administered (in absence
of contraindications)
Fibrinolytic Therapy
Recommended for STEMI patients with onset of ischemic

symptoms within 12 hours when it is anticipated that PCI cannot
be performed within 120 minutes
NOT recommended for NSTE-ACS (UA, NSTEMI)
Fibrinolytic Agents
Alteplase (t-PA)
Tenecteplase (r-PA)
Reteplase (TNK-t-PA)
ABSOLUTE Contraindications
Previous hemorrhagic stroke at any time; other strokes or
cerebrovascular events within 1 year
Known intracranial neoplasm
Active internal bleeding (not menses)
Suspected aortic dissection
Severe HTN (>180/110)
RELATIVE Contraindications
Hx of prior CVA; active PUD; or severe HTN
High likelihood of left heart thrombus
Current use of anticoagulants (INR >2-3)
Known bleeding diathesis or recent internal bleeding (within 2-4 wks)
Recent trauma (CPR) or major surgery (<3 wks)
Noncompressible vascular punctures
Prior exposure or allergic rxn to streptokinase
Pregnancy
Fibrinolytic Therapy Adjunctive Therapy
Antiplatelet Therapy: ASA + clopidogrel

Anti-coagulation Therapy
UFH 60 U/kg bolus (max 4000U), then 12 U/kg/hr infusion; adjust aPTT to
1.5-2.0
Give to all patients getting tPA, TNK or r-PA
LMWH (enoxaparin)
<75 yrs 30 mg IV bolus, then 1 mg/kg SQ q12H (max 100 mg/dose x
first 2 SQ doses; no load and q24H if CrCl < 30 mL/min)
75 yrs - no load, 0.75 mg/kg SQ q12H (max 75 mg/dose x first 2 SQ doses)
Duration of Anticoagulation: 48 hrs-8 days or until re-vascularization

Fibrinolytic Therapy Adjunctive Therapy
Anticoagulation Therapy (continued)

Fonaparinux 2.5 mg IV bolus, then 2.5 mg SQ daily starting the next
day
avoid if ClCr is < 30 mL/min
duration up to 8 days or until revascularization
if PCI to occur, need to have UFH or LMWH
STEMI Management Summary
Fibrinolytic Therapy Primary PCI

ASA
ASA +
+ P2Y12 Inhibitor (clopidogrel,
P2Y12 Inhibitor (clopidogrel) ticagrelor, prasugrel)
+ +
Anticoagulant (Enoxaparin, Anticoagulant (UFH,
UFH, Fondaparinux) Bivalirudin, Fondaparinux)
+ +/-
Glycoprotein IIa/IIIb inhibitor
(epitifibitide, tirofiban)
Complications of MI
Pump Failure (CHF) remodeling

Recurrent ischemia and re-infarction
Arrhythmias
- V-fib/V-tach
- A-fibrillation
Death
Medications for Secondary Prevention
A Aspirin
A ACE-Inhibitor
B Beta-Blocker
C Cholesterol Lowering Agent
C Clopidogrel (Prasugrel/Ticagrelor)
Long-term Therapy: Aspirin
Low dose aspirin recommended for all ACS patients indefinitely

Reduces frequency of recurrent events, risk of death and stroke
Dose: 81-325 mg (max dose of 81 mg if taking w/ticagrelor)
Long-term Therapy: ACE-Inhibitor
Prevents ventricular remodeling and development of heart failure

Treat post-MI patients indefinitely
patients with: EF <40%, DM, HTN, renal dysfunction
lisinopril 10-40 mg QD is commonly used
Reasonable to use ACE-I in all other patients

ARBs used as an alternative if intolerant
Long-term Therapy: Beta-blockers
Helps prevent recurrent MI and sudden death

Start and continue 3 years in all patients
Reasonable to continue beyond 3 yrs
Preferred Agents
metoprolol succinate & carvedilol are 1st line in heart failure patients; shown
to mortality
metoprolol (1 selective) in pts with broncho- spastic disease;
titrate slowly
Counsel patients on initial adverse effects
- they will eventually develop tolerance
Long-term Therapy: Cholesterol Lowering
Agent
Obtain fasting lipids within 24 hrs of admit

Statins are the drug of choice
High intensity statin should be initiated/continued
Atorvastatin 80 mg daily
Rosuvastatin 20 mg daily
Long-term Therapy: P2Y12 Receptor
Inhibitor
Duration of Dual Antiplatelet therapy w/ASA + P2Y12 receptor

inhibitor:
ACS w/out PCI (medical management) up to 12 months
1 month minimum
ACS w/PCI + stent at least 12 months

Bare metal: 1 month minimum
Drug eluting: 6 month minimum
Consider clopidogrel over others (prasugrel, ticagrelor) in patients

at higher risk of bleed
Secondary Prevention: Non-Pharmacologic
Smoking cessation
Weight Loss
Physical Activity
Blood Pressure Control
Diabetes Management
Influenza/Pneumococcal Vaccine
Back to AD.
AD is now s/p PCI with stent placement. The cardiologist has

asked you to look over ADs medications in preparation for
discharge. What are your recommendations for discharge
medications?
Pre-Hospital Medications:
- ASA 325 mg daily
- Lisinopril 5 mg daily
- Glyburide 5 mg daily
- Sildenafil 25 mg prn ED
Any non-
- Atorvastatin 20 mg daily
pharmacologic
recommendations.

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Acute

PHARMACY 544: PHARMACOTHERAPY

Describe the pathophysiology of ACS including risk factors, plaque

Compare and contrast diagnosis, goals of therapy and

Estimated 15.5 million Americans 20 years of

Mortality rate in people who experience an MI 15%

What differentiates ACS from chronic

Ischemia resulting from imbalance between oxygen demand and

Plaque Disruption/Rupture Activation of extrinsic

Platelet Adhesion to site of

History and Clinical Presentation

Substernal chest pain/pressure

12-lead ECG should be performed within 10 minutes of

Absence of ECG findings does not automatically rule out

Cardiac Biomarkers biochemical markers of

Creatine kinase MB (CK-MB)

Single measurement is not adequate

CK-MB 3-6H 12-24H 2-3 days

Troponin-T 2-6H 12-48H 10-14 days

Troponin-I 2-6H 18-24H 5-7 days

Postive cardiac biomarkers help to differentiate between

Non-ST segment ST-segment

Restore blood flow to artery/cardiac tissue

Initial Treatment of ACS

Antiplatelet, Anti-ischemic, Antiplatelet, Anti-ischemic,

Long-term Medical Management

AD is a 76 yo M who presents to the ER complaining of 10/10 chest pain. Pain started

PMH: HTN, DM, former smoker (1 ppd x 20 years) Allergies: PCN

FH: Father died of stroke (age 80)

SH: retired, lives alone, spends a lot of time watching TV

Treatment of chest pain not relieved by nitroglycerin

For hypoxia and/or respiratory distress

Treatment of chest pain

Should be administered to all ACS patients as soon as

Rapid inhibition of thromboxane A2 (TXA2) platelet

Alternative if ASA contraindicated: Clopidogrel

Initiate within first 24 hours (for all ACS patients without

Early administration reduces incidence of:

Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT)

Take Home: Consider later administration of beta blockers in

Should be administered within first 24 hours to the following

ECG: sinus tachy, ST segment depression

Initial Treatment of ACS

Antiplatelet, Anti-ischemic, Antiplatelet, Anti-ischemic,

Thrombolyti PCI/Cath PCI/Cath

Long-term Medical Management

Two strategies for management of UA/NSTEMI:

How do we decide which strategy to

Patients with the following clinical features are considered very

Thrombolysis in Myocardial Infarction (TIMI) Score

For patients in BOTH the Early-Invasive and Ischemic-Guided Strategy

Recommended in addition to aspirin (Dual Antiplatelet Therapy,

Clopidogrel Ticagrelor Prasugrel

Glycoprotein IIb/IIIa receptors are located on the platelet surface

Abciximab Eptifibatide Tirofiban

Take Home Message for GP IIb/IIIa Receptor

Recommended, in addition to anticoagulation therapy,

Anticoagulation Treatment Options:

For ONLY NSTE-ACS patients undergoing PCI

Enoxaparin 1 mg/kg subcutaneous q12h

Unfractionated Heparin (UFH) 60 units/kg IV load (max 4000 units), initial

Fondaparinux 2.5 mg subcutaneous daily

Bivalirudin 0.75 mg/kg IV load prior to PCI, 1.75 mg/kg/hr

Monotherapy in PCI pts (ACUITY & HORIZON trial)