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p. 234

Figure 13-2 Evaluation algorithm for the patient presenting with acute coronary syndrome. ACS, acute coronary

syndrome; CAD, coronary artery disease; CABG, coronary artery bypass graft; CK, creatinine; ECG,

electrocardiogram; PCI, percutaneous intervention; NSTE-ACS, non-ST segment acute coronary syndrome;

STEMI, ST segment myocardial infarction. A: Positive, above the myocardial infarction limit; B: Negative, below

the myocardial infarction limit. (Adapted with permission from Spinler SA. Evolution of antithrombotic therapy used

in acute coronary syndromes. In: Richardson M et al, eds. Pharmacotherapy Self-Assessment Program.

Cardiology. 7th ed. Lenexa, KS: American College of Clinical Pharmacy; 2010:62.)

Figure 13-3 ECG changes related to STEMI. On this admission electrocardiogram (ECG), note the extensive ST

segment elevation in leads II, III, and aVF (brackets), indicating an inferior wall acute myocardial infarction

(AMI). The patient also displays reciprocal ST segment depression in leads I and aVL (arrows), which are the

lateral ECG leads and are opposite the inferior leads.

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p. 235

Figure 13-4 Cardiac biomarker elevation in acute coronary syndrome. CK, creatine kinase; MI, myocardial

infarction. a. Serial troponins and CK-MB are initially measured during the first 12 to 24 hours of onset of chest

pain and continued to be measured until the concentrations begin to decline. (Adapted with permission from

Anderson JL et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-STElevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task

Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients

With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American

College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society

of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and

the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50(7):e1–e157.)

Risk Stratification

The examination of a patient presenting with ACS begins with stratification for the

risk of death and reinfarction, taking into account the presenting signs and symptoms,

past medical history, ECG and cardiac biomarker changes. Patients can be stratified

into low, medium, or high risk for mortality, and the need for urgent coronary

angiography and PCI (Fig. 13-2). In 1967, Killip and Kimball introduced a useful,

convenient tool for early risk stratification for patients with STEMI. Higher Killip

class was found to be associated with increased in-hospital and 1-year mortality

(Table 13-1).

14 The Thrombolysis in Myocardial Infarction (TIMI) risk score was

introduced in 2000 and can be used with either STEMI or NSTE-ACS (Table 13-

1).

15,16 For STEMI, a higher risk score indicates a greater 30-day mortality rate.

Patients with STEMI are at the highest risk of death and reinfarction, and initial

treatment should proceed with immediate revascularization regardless of their risk

stratification score. “Time is tissue,” means the sooner the thrombosed artery is

opened, the lower the morality and greater amount of myocardium preserved.

Reperfusion therapy should be initiated in all eligible patients with STEMI with

symptom onset within the prior 12 hours. Primary PCI is the recommended method of

reperfusion. The ACC/AHA guidelines define a target time to initiate reperfusion for

STEMI within 30 minutes of hospital presentation for fibrinolytic therapy and within

90 minutes from presentation for PCI.

5

In the case of NSTE-ACS, a TIMI risk score of 5 to 7, 3 to 4, and 0 to 2 reflect a

high, moderate, and low risk for death, MI, or need for urgent coronary artery

revascularization, respectively (Table 13-1). A low-risk patient with negative

cardiac biomarkers may undergo a stress test or be discharged from the ED with a

diagnostic test scheduled within 72 hours. Moderate and high-risk patients are often

admitted to the hospital for pharmacologic treatment, further diagnostic tests, and

angiography with possible intervention. Additional risk stratification tools such as

the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using

Integrilin Therapy (PURSUIT) risk score and Global Registry of Acute Cardiac

Events (GRACE) risk score exist for in-hospital and 1-year morality.

1,5 Other risk

scores are available to predict bleeding in patients with ACS.

17

Complications

The primary complications of ACS can be divided into three major groups: pump

failure, arrhythmias, and recurrent ischemia and reinfarction. Depression of cardiac

function after AMI is related directly to the extent of LV damage. As a result of

decreased cardiac output and decreased perfusion, a number of compensatory

mechanisms become activated. The levels of circulating catecholamines increase in

an attempt to increase contractility and restore normal perfusion. In addition, the

renin-angiotensin-aldosterone system is enhanced, leading to an increase in systemic

vascular resistance and sodium and water retention. These compensatory mechanisms

can eventually worsen the imbalance between myocardial oxygen supply and

consumption by increasing the myocardial oxygen demand.

18

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Table 13-1

Risk Stratification Tools for Acute Coronary Syndrome

TIMI Risk Score

a

STEMI NSTE-ACS

Risk Factor No. of Points Risk Factor No. of Points

Age 65–74 years 2 Age ≥ 65 years 1

Age ≥ 75 years 3 ≥3 risk factors for CAD

b 1

SBP < 100 mm Hg 3 Prior history of CAD

c 1

Heart rate > 100

beats/minute

2 Aspirin use in past 7 days 1

Killip class II–IV 2 ≥2 anginal events in past 24 hours 1

Weight < 67 kg 1 ST segment deviation ≥ 0.5 mm 1

History of HTN,

diabetes, or angina

1 Elevation of cardiac markers

d 1

Time to reperfusion

therapy >4 hours

1

Anterior ST segment

elevation or left

bundle branch block

1

Killip Class

e

Class Symptoms In-Hospital and 1-Year Mortality (%)

I No heart failure 5

II Mild heart failure, rales, S3

, congestion on

chest radiograph

21

III Pulmonary edema 35

IV Cardiogenic shock 67

aTIMI risk score data from Antman EM et al. The TIMI risk score for unstable angina/non-ST elevation MI: a

method for prognostication and therapeutic decision making. JAMA. 2000;284:835; Morrow DA et al. Application

of the TIMI risk score for ST-elevation MI in the National Registry of Myocardial Infarction 3. JAMA.

2001;286:1356. A risk score is calculated by adding the total number of risk factors. Total points for STEMI are 0–

14, in which risk scores of 0, 2, 4, 6, 7, and >8 correspond to a 30-day mortality rate of 0.8%, 2.2%, 7.3%, 16%,

23%, and 36%, respectively. Total points for NSTE-ACS are 0–7, in which scores of 0 or 1, 3, 5, and 7 correspond

to a 3%, 5%, 12%, or 19% risk of death or repeat MI at 14 days, respectively. When risk stratifying, scores of 0 to

2, 3 to 4, and 5 to 7 represent low, moderate, and high risk for death or repeat MI at 14 days.

bRisk factors include smoking, diabetes, hypertension, family history of coronary artery disease, and

hypercholesterolemia.

cDefined as a prior coronary stenosis ≥50%; history of previous myocardial infarction, percutaneous coronary

intervention, or coronary artery bypass graft; or chronic stable angina pectoris associated with a positive exercise

tolerance test or pharmacologically induced nuclear imaging or echocardiographic changes (positive nuclear

imaging or echocardiographic changes required if female).

dEither troponin I or T or creatine kinase-MB.

eKillip class data from Killip T 3rd, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two

year experience with 250 patients. Am J Cardiol. 1967;20:457.

CAD, coronary artery disease; HTN, hypertension; NSTE-ACS, non–ST segment elevation acute coronary

syndrome; SBP, systolic blood pressure; STEMI, ST segment elevation myocardial infarction; TIMI, Thrombolysis

in Myocardial Infarction.

Signs and symptoms of HF are common in patients who have abnormal wall

motion affecting 20% to 25% of the LV. If 40% or more of the LV is damaged,

cardiogenic shock and death may occur. Ischemia and scar formation after an AMI

may lead to a decrease in ventricular compliance, resulting in abnormally high LV

filling pressures during diastole. (See Chapter 14, Heart Failure, for further

discussion on HF with reduced ejection fraction and preserved ejection fraction.)

Decreased contractility and a compensatory increase in LV end-diastolic volume

and pressure lead to increased wall stress within the left ventricle. LV enlargement is

an important determinant of mortality after AMI. During a period of days to months

after an AMI, the infarcted area may expand as a result of dilatation and thinning of

the LV wall. These changes are known as ventricular remodeling. In addition,

hypertrophy of the noninfarcted myocardium occurs. Administration of oral

angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers

(ARBs), or aldosterone antagonists may limit remodeling and will attenuate the

progression of LV dilatation.

19,20

During the peri-infarction period, the heart is irritable and subject to ventricular

arrhythmias. The continuous monitoring of patients in a coronary care unit has

reduced the in-hospital mortality rate related to ventricular arrhythmias. However,

patients who have had an AMI have an increased risk of sudden cardiac death for 1

to 2 years after hospital discharge. The most important predictor for sudden cardiac

death is an abnormal LV ejection fraction (LVEF). Other factors associated with an

increased risk for sudden cardiac death are complex ventricular ectopy, frequent

(>10/hour) premature ventricular complexes, and the identification of late potentials

on a signal-averaged ECG.

18

OVERVIEW OF DRUG AND NONDRUG THERAPY

Overlap exists regarding the pharmacotherapy for both STEMI and NSTE-ACS.

According to the ACC/AHA guidelines, early therapies should consist of oxygen (if

oxygen saturation is <90%), sublingual

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(SL) and/or intravenous (IV) nitroglycerin (NTG), IV morphine, ACE inhibitor or

ARB, aldosterone antagonist, antiplatelet agents, stool softener, β-blocker, statin, and

anticoagulant. Adjunctive therapies such as analgesics and vasodilators can also be

considered in selected patients. Table 13-2 summarizes the evidence-based

pharmacotherapies for both STEMI and NSTE-ACS. Figure 13-5 provides an initial

treatment algorithm for patients with STEMI, and Figure 13-6, for patients with

NSTE-ACS. Administration of these pharmacotherapies serves as a performance

measure for health systems to ensure effective, timely, safe, and efficient patientcentered care.

1,5

Fibrinolytic Drugs

Because the majority of STEMI cases result from the sudden occlusion of a coronary

artery, the priority is to open the occluded artery as quickly as possible. This is

accomplished by administering a fibrinolytic agent that enhances the body’s own

fibrinolytic system or by mechanically reducing the obstruction with PCI.

5

Large clinical trials have proven that administration of a fibrinolytic agent reduces

mortality. Early mortality from STEMI was reduced by approximately one-third

(from 10%–15% to 6%–10%) with fibrinolytic therapy.

5

The fibrinolytic drugs currently used for STEMI patients in the United States are

alteplase (t-PA), reteplase (r-PA), and tenecteplase (TNK). Alteplase is a naturally

occurring enzyme produced by recombinant DNA technology. It cleaves the same

plasminogen peptide bond that urokinase cleaves. However, t-PA has a binding site

for fibrin, which allows it to bind to and preferentially lyse thrombin-bound instead

of circulating plasminogen. Reteplase is a genetically modified plasminogen

activator that is similar to t-PA. Reteplase has a longer half-life, allowing it to be

administered as two bolus injections 30 minutes apart, rather than as a bolus plus

infusion. TNK is a genetically modified form of t-PA. Compared with t-PA, TNK has

a longer plasma half-life, better fibrin specificity, and higher resistance to inhibition

by plasminogen-activator inhibitor.

21,22 The pharmacologic properties and dosing

regimens are compared in Table 13-3.

Unfortunately, an ideal fibrinolytic agent does not exist. Three problems common

to all fibrinolytic drugs are the inability to open 100% of coronary artery occlusions,

inconsistent ability to maintain good blood flow in the infarcted artery after it is

opened, and bleeding complications. When assessing coronary artery flow after

reperfusion therapy, the TIMI flow grade is used. Flow in coronary arteries is

classified as grade 0 (no flow), grade 1 (penetration without perfusion), grade 2

(partial perfusion), or grade 3 (complete perfusion).

23 When assessing an episode of

bleeding, the TIMI bleeding criteria are used. TIMI major bleeding consists of overt

clinical bleeding or documented intracranial or retroperitoneal hemorrhage that is

associated with a drop in hemoglobin of at least 5 g/dL or hematocrit of at least 15%

(absolute). TIMI minor bleeding is defined as overt clinical bleeding associated with

a fall in hemoglobin of 3 to 5 g/dL or in hematocrit of 9% to 15% (absolute).

24

To minimize the risk of bleeding complications, contraindications to the use of

fibrinolytic drugs must be evaluated before administration (Table 13-4). There are

relatively few absolute contraindications to fibrinolytic therapy, but each patient

should be assessed carefully to ascertain whether the potential benefit outweighs the

potential risk. Because of the serious nature of intracerebral hemorrhage, patients

should be selected carefully before receiving these agents. Generally, the diagnosis

of STEMI must be ensured, with a history consistent with ischemia, and presence of

ST segment elevation in two contiguous leads, or a new left bundle branch block on

the ECG. Once the diagnosis is made, the fibrinolytic agent should be administered

immediately if there are no contraindications.

5

Fibrinolytic therapy is indicated in patients with STEMI who present to the

hospital within 12 hours of symptom onset and are unable to undergo primary PCI

within 120 minutes from first medical contact.

5 The benefit derived from fibrinolytic

therapy is directly related to the time from the onset of chest pain to the time of

administration. Although the guidelines recommend initiation within 12 hours from

the onset of chest pain, data from clinical trials suggest that mortality reduction is

greater when fibrinolytic therapy is initiated within 0 to 2 hours of symptom onset

compared with treatment initiated more than 2 hours after symptoms have begun. The

guidelines recommend a “door-to-needle time” of 30 minutes, meaning the diagnosis

of STEMI and initiation of fibrinolytic therapy should ideally take place within 30

minutes from the time the patient arrives at the hospital door. Once stabilized, the

patient should be transferred to a facility capable of PCI in case reperfusion fails or

reocclusion occurs.

5

In patients with NSTE-ACS, fibrinolytic agents are not recommended. Thrombi in

this population are primarily platelet-rich rather than fibrin-rich, and less responsive

to fibrinolytic therapy.

25 Additionally, data from the TIMI IIIB trials suggest that

compared with placebo, alteplase was not associated with any improvement in death,

MI, or failure of initial therapy and was associated with an increased incidence in

fatal and nonfatal MI.

26

Antiplatelet and Anticoagulant Drugs

When thrombolysis occurs, whether because of the administration of a fibrinolytic

agent or through activation of the body’s own fibrinolytic system, the fibrin clot

begins to disintegrate. As the clot dissolves, there is a paradoxical increase in local

thrombin generation and enhanced platelet aggregability, which may lead to

rethrombosis. Antiplatelet agents (aspirin, P2Y12

receptor antagonists: clopidogrel,

prasugrel, or ticagrelor, and the glycoprotein [GP] IIb/IIIa inhibitors), as well as

parenteral anticoagulants (unfractionated heparin [UFH], low-molecular-weight

heparins [LMWH] such as enoxaparin, and direct thrombin inhibitors [DTIs] such as

bivalirudin), have been used to minimize rethrombosis. UFH has several limitations,

including a highly variable anticoagulant effect necessitating frequent monitoring and

development of heparin-induced thrombocytopenia (<0.2%). LMWH may offer

advantages compared with heparin owing to its ease of administration, improved

bioavailability, and need for less monitoring. Unlike UFH, the DTIs offer better

protection against thrombin reactivation after therapy discontinuation.

The GP IIb/IIIa receptor inhibitors, which are tirofiban, eptifibatide, and

abciximab are also used. Glycoprotein IIb/IIIa receptors are abundant on the platelet

surface. Platelets become activated when patients are having an acute ischemic event

or are undergoing PCI. With platelet activation, the GP IIb/IIIa receptor undergoes a

conformational change that increases its affinity for binding fibrinogen. The binding

of fibrinogen to receptors on platelets results in platelet aggregation, leading to

thrombus formation. The GP IIb/IIIa receptor inhibitors prevent platelet aggregation

by preventing fibrinogen from binding to GP IIb/IIIa receptor sites on activated

platelets.

5

Acute thrombocytopenia is a rare but recognized side effect of all three agents, but

seen more often with abciximab.

27 The GP IIb/IIIa inhibitors are used in conjunction

with other antiplatelet drugs and anticoagulants in patients with NSTE-ACS and in

patients undergoing PCI. Although effective when used in conjunction with

fibrinolytic agents for patients with STEMI, the benefit is offset by high rates of

bleeding. Therefore, routine use of GP IIb/IIIa inhibitors is not recommended with

fibrinolytics.

5

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Table 13-2

Evidenced-based Pharmacotherapies for Acute Coronary Syndromes

1,5

Drug Indication Dose and Duration

Therapeutic

End Points Precautions Comments

ACE

inhibitors

a

STEMI and

NSTE-ACS

within the first 24

hours of

presentation for

those with EF

≤40% or s/s of

HF

STEMI and

NSTE-ACS for

late hospital care

for patients with

hypertension, EF

≤ 40%, DM, or

CKD

STEMI and

NSTE-ACS for

indefinite use for

all patients with

EF ≤40%.

Usual captopril dose

12–50 mg TID, then

start longer-acting

ACE inhibitor. Duration

indefinite.

Titrate to

usual doses

and maintain

systolic BP >

90 mm Hg.

Avoid IV therapy

within 48 hours

of infarct.

Avoid initiation

with systolic BP

<100 mm Hg,

pregnancy, acute

renal failure,

angioedema,

bilateral renal

stenosis, serum

potassium ≥ 5.5

mEq/L.

Angiotensin

receptor

blockers

a

STEMI and

NSTE-ACS with

ACE inhibitor

intolerance.

Usual doses of ARBs

(see Chapter 14, Heart

Failure). Duration

indefinite.

Same as for

ACE

inhibitors.

Same as for

ACE inhibitors.

Aldosterone

antagonists

a

STEMI and

NSTE-ACS with

EF ≤40% and

either DM or HF

symptoms

already receiving

therapeutic doses

of an ACE

inhibitor and βblocker.

Spironolactone 12.5–50

mg daily or eplerenone

25–50 mg daily.

Duration indefinite.

Titrate to

heart failure

symptom

control without

evidence of

hyperkalemia

Hyperkalemia,

hypotension

Avoid if

potassium ≥ 5

mEq/L or SCr ≥

2.5 mg/dL for

men and 2.0

mg/dL for

women or CrCl

≤30 mL/minute

Dose can be

increased

every 4–8

weeks.

Aspirin

a STEMI and

NSTE-ACS for

all patients.

162–325 mg during

AMI, then 81–325 mg

daily indefinitely (81 mg

daily is preferred).

Active bleeding,

thrombocytopenia

Unless clear

contraindication

exists, aspirin

should be given

to all AMI

patients.

Amiodarone Treatment of

VT, VF.

150 mg IV over 10

minutes, repeat for

recurrence, follow with

1 mg/minute IV

infusion for 6 hours,

then 0.5 mg/minute

(maximum: 2.2 g/24

hours).

Cessation of

arrhythmia.

Bradycardia,

hypotension.

β-Blockers

a STEMI and

NSTE-ACS in all

patients without

contraindications.

Variable. Titrate to HR

and BP. It is

reasonable to

administer an IV βblocker at the time of

presentation to STEMI

patients who are

hypertensive and who

do not have any of the

following: (a) signs of

heart failure, (b)

evidence of a low

output state, (c)

increased risk for

cardiogenic shock

b

, or

(d) other relative

contraindications to βblockade (PR interval >

0.24 second, second- or

third-degree heart

block, active asthma, or

reactive airway

disease). Duration

indefinite.

Titrate to

resting HR

approx. 60

beats/minute,

maintain

systolic BP

>100 mm Hg.

Observe HR and

BP closely when

given IV

Contraindicated

in patients with

HR <50

beats/minute; PR

ECG interval

>0.24 second,

second- or thirddegree heart

block, persistent

hypotension,

pulmonary

edema,

bronchospasm,

risk of

cardiogenic

shock, severe

reactive airway

disease.

Unless clear

contraindication

exists, β1

-

selective

agents such as

metoprolol and

atenololshould

be given to all

AMI patients.

In patients with

systolic

dysfunction,

metoprolol,

carvedilol, or

bisoprolol can

be considered.

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p. 239

Bivalirudin

a STEMI with

primary PCI

and NSTEACS with an

early invasive

strategy.

STEMI with primary

PCI: 0.75 mg/kg IV

bolus immediately prior

to PCI, followed by 1.75

mg/kg/hour infusion

with or without UFH.

NSTE-ACS with an

early invasive strategy:

0.1 mg/kg IV bolus

followed by 0.25

mg/kg/hour infusion.

Continue until diagnostic

angiography or PCI is

performed.

Avoid in patients

with active

bleeding.

Reduce

infusion to 1

mg/kg/hour

with estimated

CrCl <30

mL/minute.

Cangrelor

a STEMI and

NSTE-ACS

before PCI in

patients not

treated with a

P2Y12

platelet

inhibitor and

are not being

given a GP

IIb/IIIa

inhibitor.

30 μg/kg IV bolus prior

to PCI followed

immediately by a 4

μg/kg/minute IV

infusion for at least 2

hours or duration of

procedure, whichever is

longer

Active bleeding After

discontinuation

of infusion, an

oral P2Y12

platelet

inhibitor should

be

administered:

ticagrelor 180

mg load during

or upon

immediate

discontinuation

of infusion;

prasugrel 60

mg or

clopidogrel 600

mg upon

immediate

discontinuation

of infusion.

Calciumchannel

blockers

STEMI and

NSTE-ACS for

patients with

ongoing

ischemia who

are receiving

adequate doses

of nitrates and

β-blockers.

Consider

diltiazem or

verapamil for

patients with

contraindication

to β-blocker if

EF normal.

Usual doses of calciumchannel blockers are

used. Duration dictated

by clinicalscenario.

Titrate to

usual doses

and maintain

systolic BP

>90 mm Hg

Usual calciumchannel blocker

contraindications.

Avoid

nondihydropyridines

in patients with

pulmonary

congestion or EF

<40% or AV block.

In patients

with normal

EF, most

calciumchannel

blockers will

exert

beneficial

effects.

Some data

support use of

verapamil or

diltiazem for

non–Q-wave

AMI.

Clopidogrel

a STEMI and

NSTE-ACS for

patients allergic

75 mg daily. Active bleeding,

thrombotic

thrombocytopenia

to aspirin. purpura (rare).

Clopidogrel +

aspirin

a

STEMI with

fibrinolytic

therapy, before

PCI after

fibrinolytic

therapy, or

before primary

PCI. NSTEACS for early

invasive or

ischemiaguided

strategies.

STEMI with fibrinolytic

therapy: 300 mg load,

then continue 75 mg

daily, and continue for

up to 1 year; aspirin

162–325 mg on first

day, then 81–325 mg

daily indefinitely (81 mg

daily is preferred).

Active bleeding,

thrombotic

thrombocytopenia

purpura (rare),

avoid loading dose

in patients ≥75

years of age,

discontinue at least

5 days for CABG.

Whether

administered

before

fibrinolytic or

PCI,

clopidogrel +

aspirin reduced

CV death, MI,

or ischemia at

30 days. The

600 mg load

should be

considered if a

GP IIb/IIIa is

not used.

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p. 240

STEMI with fibrinolytic

therapy with PCI: if PCI <

24 hours from fibrinolytic,

then 300 mg load and for

>24 hours from fibrinolytic,

600 mg load, then continue

75 mg daily if coronary

stent deployed for at least

1 year; aspirin 162–325

mg on first day, then 81–

325 mg daily indefinitely

(81 mg is preferred).

STEMI before primary

PCI: 600 mg load, then

continue 75 mg daily if

coronary stent deployed

for at least 1 year; aspirin

162–325 mg on first day,

then 81–325 mg/day

indefinitely. (81 mg daily is

preferred.)

NSTE-ACS for early

invasive or ischemiaguided strategy: 300–600

mg load, then continue 75

mg daily for at least 1

year; aspirin 162–325 mg

on first day, then 81–325

mg/day indefinitely. (81

mg daily is preferred).

Enoxaparin

a STEMI (as an

alternative for

UFH) for

STEMI with fibrinolytic

therapy: Age <75 years,

administer 30 mg IV bolus

Avoid in

patients with

active bleeding,

For CrCl 15–

29 mL/minute

reduce to 1

patients

receiving

fibrinolytic

therapy or for

those not

undergoing

PCI.

NSTE-ACS

for early

invasive or

ischemiaguided

strategies.

followed by 1 mg/kg SQ

every 12 hours (max dose

of 100 mg for patients

weighing ≥100 kg).

Age ≥75, administer 0.75

mg/kg SQ every 12 hours

(first two doses administer

max dose of 75 mg for

patients weighing ≥75 kg).

Continue up to 8 days or

until revascularization.

NSTE-ACS for early

invasive or ischemiaguided strategies: 1 mg/kg

SQ every 12 hours. A

supplemental 0.3 mg/kg IV

dose should be

administered at the time of

PCI if the last dose of SC

enoxaparin was given 8–

12 hours before PCI.

Continue for duration of

hospitalization or until PCI.

history of HIT,

planned

CABG, SCr ≥

2.5 mg/dL in

men and ≥2.0

mg/dL in

women, or

CrCl <15

mL/minute.

mg/kg every

24 hours.

p. 240

p. 241

Fibrinolytic

therapy

a

STEMI

presenting within

12 hours after

onset of

symptoms, can be

considered in

patients

presenting within

12–24 hours after

onset of

symptoms with

continuing s/s of

ischemia.

See Table 13-3. Improved

TIMI grade

flow.

See Table 13-4.

Fondaparinux

a STEMI:

alternative for

UFH or LMWH

in patients

receiving

fibrinolytic

therapy or in

those not

undergoing PCI.

NSTE-ACS:

alternative for

UFH or LMWH

for early invasive

STEMI: 2.5 mg SQ

daily starting on day 2

of hospitalization,

continue for 8 days or

until revascularization.

NSTE-ACS for early

invasive or ischemiaguided strategies:

2.5 mg SQ daily for

the duration of the

hospitalization or until

PCI is performed.

Avoid with active

bleeding or CrCl

< 30 mL/minute.

In STEMI,

fondaparinux

reduced

mortality and

reinfarction

without

increased

bleeding or

strokes

compared with

UFH, but only

in patients not

undergoing

or ischemiaguided strategies.

Administer

additional

anticoagulant

with factor IIa

activity in patients

undergoing PCI.

PCI.

In NSTE-ACS,

fondaparinux

was at least as

effective as

enoxaparin but

exhibited less

bleeding. Can

possibly be

used in HIT.

GP IIb/IIIa

inhibitors

a

STEMI: in

patients

undergoing PCI.

NSTE-ACS: in

patients treated

with early

invasive strategy

and DAPT with

intermediate/highrisk features.

See Table 13-6. Avoid with active

bleeding,

thrombocytopenia,

prior stroke.

In NSTE-ACS

eptifibatide or

tirofiban are

FDA approved

for PCI and

ischemiaguided therapy.

Abciximab is

only for

patients

undergoing

PCI.

Heparin

a STEMI: for

patients

undergoing PCI

or treated with

fibrinolytic

therapy.

NSTE-ACS: for

early invasive or

ischemia-guided

strategies.

STEMI with

fibrinolytic therapy or

NSTE-ACS with early

invasive or ischemiaguided strategies:

60 units/kg IV bolus

(max 4,000 units)

followed by 12

units/kg/hour (max

1,000 units/hour) for 48

hours or until

revascularization.

STEMI with PCI: 50–

70 units/kg IV bolus if

a GP IIb/IIIa inhibitor

planned; or 70–100

units/kg IV bolus if no

GP IIb/IIIa inhibitor.

Continue for 48 hours

or until end of PCI.

aPTT ratio

1.5–2.5×

patient’s

control value,

aPTT should

be obtained

4–6 hours

after initiation

of infusion if

not treated

with

fibrinolytic

therapy or

PCI and

within 3

hours if

treated with

fibrinolytic

therapy.

Avoid with active

bleeding,

thrombocytopenia,

recent stroke.

Unless clear

contraindication

exists, UFH

should be given

to all AMI

patients who do

not receive

fibrinolytic

therapy.

Morphine and

other

analgesics

STEMI and

NSTE-ACS for

patients whose

symptoms not

relieved by NTG

or adequate antiischemic therapy.

Morphine: 2–5 mg IV

every 5–30 minutes

PRN.

Decreased

chest pain

and HR.

Avoid morphine

with bradycardia,

right ventricular

infarct,

hypotension,

confusion.

Has been

associated with

higher risk of

death;

discontinue

nonselective

NSAIDs and

COX-2

selective

agents.

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p. 242

Nitroglycerin

a STEMI and

NSTE-ACS

with persistent

ischemia,

hypertension,

or pulmonary

congestion.

Variable; titrate to pain

relief or systolic BP: 5–10

mcg/minute titrated to 200

mcg/minute. Usually

maintain IV therapy for

24–48 hours after infarct.

Titrate to pain

relief or

systolic BP >

90 mm Hg

Avoid with

systolic BP <

90 mm Hg,

right

ventricular

infarction,

sildenafil or

vardenafil

within 24

hours, or

tadalafil within

48 hours.

Use

acetaminophen

or narcotics

for headache.

NTG should be

tapered

gradually in

ischemic heart

disease

patients.

Topical

patches or oral

nitrates are

useful for

patients with

refractory

symptoms.

Prasugrel +

Aspirin

a

STEMI: before

PCI after

fibrinolytic

therapy or

before primary

PCI.

NSTE-ACS:

before PCI

with coronary

stenting.

60 mg loading dose, then

10 mg daily (if ≥60 kg) or

5 mg (if <60 kg) if

coronary stent deployed

for at least 1 year; aspirin

162–325 mg on day 1, then

81–325 mg daily

indefinitely (81 mg daily is

preferred).

Avoid with

active bleeding,

prior stroke or

TIA, age ≥75

years

Do not start if

urgent CABG

needed;

discontinue 7

days before

elective CABG

or other

surgery.

Ticagrelor +

Aspirin

a

ACS: previous

history of AMI

STEMI: before

primary PCI.

NSTE-ACS:

for early

invasive or

ischemiaguided

strategies.

ACS with previous history

of MI: Load with 180 mg

oral loading dose following

an ACS event, then

continue treatment with 90

mg twice daily during the

first year after an ACS

event. After 1 year,

administer 60 mg twice

daily; aspirin 162–325 mg

on day 1, then 81 mg daily

indefinitely.

STEMI before primary

PCI:180 mg load, then

continue 90 mg BID if

coronary stent deployed

for at least 1 year; aspirin

162–325 mg on day 1, then

81 mg daily indefinitely.

NSTE-ACS with early

No firm end

points

Avoid in

patients with

severe hepatic

impairment or

active

bleeding.

Maintenance

doses of

aspirin above

100 mg daily

can decrease

ticagrelor’s

effectiveness,

Discontinue at

least 5 days

prior to

CABG.

Monitor

closely for

dyspnea.

For at least the

first 12 months

following ACS,

ticagrelor was

found to be

superior to

clopidogrel.

Maximum

dose of

simvastatin is

40 mg with

ticagrelor.

invasive or ischemiaguided strategy: 180 mg

load, then continue 90 mg

BID if coronary stent

deployed or for both early

invasive or ischemiaguided strategies for at

least 1 year; aspirin 162–

325 mg on day 1, then 81

mg daily indefinitely.

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p. 243

Vorapaxar ACS for

secondary

prevention of

thrombotic

cardiovascular

events.

1 tablet (2.08 mg) daily. Contraindicated

in history of

stroke, TIA,

ICH, or active

bleeding.

Use with

aspirin and/or

clopidogrel

according to

their

indications or

standard of

care. No data

with ticagrelor

or prasugrel or

as use as a

single

antiplatelet

agent.

Warfarin STEMI and

NSTE-ACS for

left ventricular

thrombus or for

patients with AF

with

CHA2DS2VASc

score ≥ 2.

Variable; titrate to INR.

Duration usually

dependent upon

indication for warfarin.

INR goal 2–3.

If receiving

DAPT, then

consider INR

goal to 2.0–2.5

or discontinue

aspirin.

Usual warfarin

problems such

as

noncompliance

and bleeding

diathesis.

May be useful

in the

presence of a

left ventricular

thrombus or

atrial

fibrillation to

prevent

embolism.

ACE, angiotensin-converting enzyme; AF, atrial fibrillation; AMI, acute myocardial infarction; aPTT, activated

partial thromboplastin time; ARBs, angiotensin receptor blockers; BID, twice daily; BP, blood pressure; CABG,

coronary artery bypass graft; CHA2DS2VASc, risk score for atrial fibrillation comprising age, sex, HF,

hypertension, stroke/TIA/thromboembolism, vascular disease, and DM; CKD, chronic kidney disease; CNS,

central nervous system; COX-2, cyclooxygenase-2; CrCl, creatinine clearance; CV, cardiovascular; DAPT, dual

antiplatelet therapy; DM, diabetes mellitus; ECG, electrocardiogram; EF, ejection fraction; FDA, Food and Drug

Administration; GP IIb/IIIa, glycoprotein IIb/IIIa inhibitor; HF, heart failure; HIT, heparin-induced

thrombocytopenia; HR, heart rate; INR, international normalized ratio; ICH, intracranial hemorrhage; IV,

intravenous; LMWH, low-molecular-weight heparin; MI, myocardial infarction; NSAIDs, nonsteroidal

antiinflammatory drugs; NSTE-ACS, non–ST segment elevation acute coronary syndrome; NTG, nitroglycerin;

PCI, percutaneous coronary intervention; PRN, as needed; SCr, serum creatinine; SQ, subcutaneously; s/s, signs

and symptoms; STEMI, ST segment elevation myocardial infarction; TIA, transient ischemic attack; TID, 3 times a

day; TIMI, Thrombolysis in Myocardial Infarction; UHF, unfractionated heparin; VF, ventricular fibrillation; VT,

ventricular tachycardia.

a

Indicates specific drug therapies that are known to reduce morbidity or mortality.

bRisk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of

developing cardiogenic shock) are age >70 years, systolic BP < 120 mm Hg, sinus tachycardia >110 beats/minute,

or HR < 60 beats/minute.

p. 243

p. 244

Figure 13-5 Initial treatment algorithm for STEMI. a: Early hospital care consists of oxygen for oxygen saturation

<90%, SL nitroglycerin, IV nitroglycerin, IV morphine, β-blocker, ACE inhibitor or ARB, aldosterone antagonist,

stoolsoftener, and statin. b: Refer to Table 13-2 for indications, dosing, and contraindications. c: For at least 48

hours. d: For the duration of the hospitalization, up to 8 days. ACE, angiotensin-converting enzyme; ARB,

angiotensin receptor blocker; CABG, coronary artery bypass graft; GP IIb/IIIa, glycoprotein IIB/IIIA; NTG,

nitroglycerin; O2

, oxygen; PCI, percutaneous coronary intervention; SL, sublingual; STEMI, ST segment elevation

myocardial infarction; UFH, unfractionated heparin. (Source: Kushner FG et al. 2009 focused updates: ACC/AHA

guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and

2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005

guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart

Association Task Force on Practice Guidelines [published corrections appear in J Am Coll Cardiol. 2010;55:612

(dosage error in article text); J Am Coll Cardiol. 2009;54:2464]. J Am Coll Cardiol. 2009;54:2205; Anderson JL et

al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial

infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice

Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable

Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of

Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic

Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society

for Academic Emergency Medicine [published correction appears in J Am Coll Cardiol. 2008;51:974]. J Am Coll

Cardiol. 2007;50:e1; O’Gara PT et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial

infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on

Practice Guidelines. Circulation. 2013;127(4):e362–e425.)