ch.008

86

Acute Coronary SyndromesPaul F. Frey, MD, MPH; and Richard Lange, MD

FAST FACTS

� Acute coronary syndrome (ACS) consists of the signs and symptomscompatible with progressive or acute nonexertional myocardialischemia and is divided into non–ST segment elevation ACS and STsegment elevation ACS.

� Risk stratification is important in guiding therapy for patients withnon–ST segment elevation ACS.

� The electrocardiographic (ECG) diagnosis of ST segment elevationACS is defined by more than 1 mm of ST segment elevation in two limb leads, more than 2 mm of ST segment elevation in twocontiguous precordial leads, or a new or presumed new left bundlebranch block.

� In the patient with ST segment elevation ACS, prompt reperfusion ofthe infarct-related artery (IRA) is essential.

� Aggressive risk factor modification and secondary prevention therapyshould be applied to all patients with ACS.

1. Cardiovascular disease is the leading cause of death in the UnitedStates, accounting for more than 1 of every 5 deaths. Each year,approximately 1.7 million patients are hospitalized in the United Stateswith ACS.1

2. ACS consists of the signs and symptoms of myocardial ischemia thatoccur at rest or with minimal exertion and usually is caused by ruptureof a coronary atherosclerotic plaque, with subsequent plateletaggregation and coronary thrombosis.

3. The management of ACS depends on ECG findings. Patients with ST segment elevation probably have total occlusion of anepicardial coronary artery and should receive prompt reperfusion of the IRA, whereas patients with ACS and without ST segmentelevation probably have subtotal occlusion of an epicardial coronaryartery and should receive intense antiplatelet and anticoagulant therapy. Cardiac catheterization should be performed in those at high risk for myocardial infarction (MI) or death on the basis of riskstratification.

I. CLINICAL PRESENTATIONThe history, physical examination, ECG findings, and cardiac biomarkersare used to determine whether the patient with chest pain has ACS (Table 8-1). Important historical features include the following:

8

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Acute Coronary Syndromes 87

8

AC

UTE

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RY

SYN

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TAB

LE 8

-1LI

KEL

IHO

OD

TH

AT S

IGN

S A

ND

SYM

PTO

MS

REP

RES

ENT

AC

UTE

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RO

NA

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SYN

DR

OM

E SE

CO

ND

AR

Y TO

CA

DIn

term

edia

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ikel

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f Lo

w L

ikel

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d (a

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f hi

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orhi

gh-li

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ures

and

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senc

e in

term

edia

te-li

kelih

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feat

ures

but

may

H

igh

Like

lihoo

d (a

ny o

f th

e fo

llow

ing)

of a

ny o

f th

e fo

llow

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have

the

fol

low

ing)

His

tory

Ches

t or

left

arm

pai

n or

dis

com

fort

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est

or le

ft ar

m p

ain

or d

isco

mfo

rt

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able

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sym

ptom

s in

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ence

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as c

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rodu

cing

as c

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of t

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r do

cum

ente

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gina

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yr

char

acte

ristic

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now

n hi

stor

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clud

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xR

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t co

cain

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em

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l inf

arct

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bete

s m

ellit

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al r

egur

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iac

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t di

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alpa

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tens

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dia

phor

esis

, pu

lmon

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a, o

r ra

les

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troca

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sum

ably

new

, tra

nsie

nt S

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xed

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aves

T w

ave

flatte

ning

or

inve

rsio

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lead

s w

ithse

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t de

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(>0.

05 m

V) o

r Ab

norm

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gmen

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dom

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ithw

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nes

RH

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al:

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tabl

e an

gina

: di

agno

sis

and

man

agem

ent,

Roc

kvill

e, M

d, 1

994,

Age

ncy

for

Hea

lth C

are

Polic

y an

d R

esea

rch

and

the

Nat

iona

l Hea

rt,

Lung

, an

d B

lood

Ins

titut

e, U

.S.

Publ

ic H

ealth

Ser

vice

, U

.S.

Dep

artm

ent

of H

ealth

and

Hum

an S

ervi

ces;

AH

CPR

Pub

licat

ion

No.

94-

0602

.C

AD

,co

rona

ry a

rter

y di

seas

e.

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1. Quality and frequency of chest discomfort. Chest discomfort moresevere than the patient’s usual chest pain or occurring more frequentlysuggests ACS.

2. Rest pain. Chest discomfort occurring at rest or with minimal activitysuggests ACS.

3. Duration of chest pain. Stable angina rarely causes chest discomfortlonger than 10 minutes. Chest pain lasting longer is more likely toindicate ACS.

4. Prior cardiac history. Patients with chest pain within 2 months of anMI or coronary revascularization have ACS until proven otherwise.

5. Associated symptoms. Diaphoresis, shortness of breath, palpitations,and nausea often accompany chest pain caused by ACS.

II. DIAGNOSISAll patients being evaluated for ACS should be placed on a cardiacmonitor, and a 12-lead electrocardiogram should be obtained within 10minutes of presentation and repeated if the chest discomfort changes. A careful physical examination (including assessment of blood pressure in both arms) should be performed and a chest film obtained. A bloodsample should be sent for analysis of the comprehensive metabolic panel,troponin level, fractionated creatine kinase (CK) concentration, completeblood cell count, and prothrombin and activated partial thromboplastintimes. Risk stratification of the patient should then be used.A. ELECTROCARDIOGRAM1. A 12-lead electrocardiogram should be obtained immediately for every

patient with signs or symptoms suggestive of ACS and compared with aprevious electrocardiogram if available.

2. The electrocardiogram differentiates ST segment elevation ACS fromnon–ST segment elevation ACS. This distinction is vital becausetreatment differs greatly between the two syndromes.

3. The current ECG criteria for the diagnosis of ST elevation ACS requiremore than 1 mm ST elevation in two or more anatomically contiguouslimb leads, more than 2 mm ST elevation in two or more anatomicallycontiguous precordial leads, or a new or presumed new left bundlebranch block.

4. Serial ECG analysis is essential because a suspected non–ST segmentelevation ACS may evolve into an ST segment elevation ACS.

5. A right-sided electrocardiogram should be obtained in all patients withST segment elevations in the inferior leads to determine whether rightventricular MI is present. ST segment elevation in V4 of the right-sidedleads suggests a right ventricular infarction.

6. When the electrocardiogram meets ST segment elevation ACS criteria,the patient becomes eligible for acute reperfusion therapy. The currentrecommendations are to administer thrombolytic therapy within 30minutes or perform percutaneous coronary intervention (PCI) within 90 minutes of diagnosis.

88 Cardiology

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7. Patients with non–ST segment elevation ACS may initially have anormal electrocardiogram or nonspecific ST-T wave changes. Thus anormal electrocardiogram does not exclude this diagnosis. ST segmentdepressions of more than 1 mm in two or more contiguous limb leads(or more than 2 mm in two or more contiguous precordial leads) maybe present and predict adverse cardiac events.

B. CARDIAC BIOMARKERS1. In patients with a non–ST segment elevation ACS, serum biomarkers

(e.g., cardiac enzymes) indicative of myocardial necrosis are helpful instratifying risk and differentiating ischemia from infarction. It takesseveral hours from the time myocardial injury occurs until biomarkersare detectable in the serum, so the patient with a non–ST segmentelevation ACS may have normal values initially at presentation.Therefore blood samples should be obtained at the time of presentationand again 6 to 12 hours later.

2. Traditional biomarkers included CK, troponin I or T, and myoglobin.Based on current guidelines, the cardiac-specific troponins such astroponin T and troponin I are the preferred markers. Troponin T isdetectable in the serum within 4 hours after myocardial injury, withelevated serum levels for 7 to 10 days. Troponin I is typically detectablewithin 6 hours of myocardial injury, and the serum levels remainelevated for 7 to 10 days. Troponin I is less likely to be associated withfalse elevations than troponin T in patients with renal insufficiency.

3. CK exists in three isoforms (MM, MB, BB), of which CK-MB is cardiac-specific. CK-MB serum levels typically increase 3 to 6 hours aftermyocardial injury, peak at 12 to 24 hours, and return to normal within3 days. CK-MB is less cardiospecific than troponin, and serum levelsmay be elevated in the patient with trauma, surgery, rhabdomyolysis,sepsis, hypothyroidism, or renal dysfunction.

4. Myoglobin is a highly sensitive and early marker of myocardial damage.Serum myoglobin levels begin to increase within 2 hours of myocardialinjury and peak at 24 hours. However, serum myoglobin has very lowspecificity because myoglobin increases with skeletal muscle injury,trauma, intramuscular injections, alcohol abuse, renal dysfunction, andhypothermia or hyperthermia. Therefore a negative myoglobin within 8 hours of the onset of chest pain may be useful to help rule outmyocardial ischemia.

III. MANAGEMENT: NON–ST SEGMENT ELEVATION ACSA. RISK STRATIFICATIONRisk stratification is integral in the management of a non–ST segmentelevation ACS because not all patients with ACS are equally likely to haveadverse cardiac events (i.e., death, MI, or urgent revascularization).Patients are classified as being at high, intermediate, or low risk of havingan adverse cardiac event, and therapy is tailored to the patient’s riskprofile. The following clinical tools help risk stratify patients:


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90 Cardiology

1. Electrocardiogram and cardiac biomarkers. ST segment depression andelevated cardiac biomarkers are associated with a higher risk of adverseoutcomes. Patients with only one of the two are at intermediate risk,and those with neither are at low risk.

2. A list of historical and physical findings the American Heart Associationhas adopted in assisting with risk stratification is provided in Table 8-2.

3. Thrombolysis in Myocardial Infarction (TIMI) risk score assessment.The TIMI risk factor score predicts the probability of adverse cardiacoutcomes in patients with non–ST segment elevation ACS based ondata available at the bedside.2 Seven variables are assessed (Box 8-1),with the likelihood of an adverse cardiac event predicted by the numberof variables present. Patients with a score of less than 3 are at low risk,those with a score of 3 or 4 are at intermediate risk, and those with ascore of 5 or higher are at high risk for having a cardiac event over thenext 30 days.

B. INTERVENTION: PHARMACOLOGIC AND NONPHARMACOLOGIC1. The management of non–ST segment elevation ACS is based on risk

stratification. All patients initially are treated with aspirin, beta-blockers,nitrates, and anticoagulation unless contraindicated. Once thesetherapies are initiated, the first decision is whether the patient shouldundergo early invasive or noninvasive management. The next decisionis whether the patient should receive clopidogrel or a glycoprotein (GP)IIb/IIIa inhibitor.

BOX 8-1THROMBOLYSIS IN MYOCARDIAL INFARCTION RISK FACTOR SCORERISK FACTORS

Age >65 yearsThree or more risk factors for coronary artery diseasePrior coronary stenosis ≥50%Two or more anginal events in past 24 hrAspirin use in past 7 dST segment changesPositive cardiac markers30-DAY RISK OF ADVERSE CARDIAC EVENT*Number of Risk Factors Risk (%)0-1 4.72 8.33 13.24 19.95 26.26-7 41.0

Data from Antman E et al: JAMA 284:835, 2000.*Defined as myocardial infarction, cardiac-related death, or persistent ischemia. Low risk, score0-2; intermediate risk, score 3-4; high risk, score 5-7.

A03748-ch008.qxd 2/7/06 9:33 PM Page 90


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TAB

LE 8

-2SH

OR

T-TE

RM

RIS

K O

F D

EATH

OR

NO

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CA

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IAL

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RC

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N I

N P

ATIE

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NST

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w R

isk

(no

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erm

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isk

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isk

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isk

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but

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hav

e an

y of

the

fe

atur

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ust

be p

rese

nt)

but

mus

t ha

ve 1

of

the

follo

win

g)fo

llow

ing

feat

ures

)H

isto

ryAc

cele

ratin

g te

mpo

of

isch

emic

Pr

ior

MI,

perip

hera

l or

cere

brov

ascu

lar

sym

ptom

s in

pre

cedi

ng 4

8 hr

dise

ase,

or

coro

nary

art

ery

bypa

ss

graf

t; pr

ior

aspi

rin u

seCh

arac

ter

of p

ain

Prol

onge

d (>

20 m

in)

rest

pai

nPr

olon

ged

(>20

min

) re

st a

ngin

a, n

owN

ew-o

nset

Can

adia

n Ca

rdio

vasc

ular

re

solv

ed,

with

mod

erat

e or

hig

hSo

ciet

y Cl

ass

III o

r IV

ang

ina

in

likel

ihoo

d of

CAD

; re

st a

ngin

a th

e pa

st 2

wk

with

out

prol

onge

d

(<20

min

) or

rel

ieve

d w

ith r

est

or(<

20 m

in)

rest

pai

n bu

t w

ith m

oder

ate

subl

ingu

al n

itrog

lyce

rinor

hig

h lik

elih

ood

of C

ADCl

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al f

indi

ngs

Pulm

onar

y ed

ema,

pro

babl

y du

e to

Age

>70

yea

rsis

chem

ia;

new

or

wor

seni

ng m

itral

regu

rgita

tion

mur

mur

; S 3

; or

new

or

wor

seni

ng r

ales

Hyp

oten

sion

Bra

dyca

rdia

or

tach

ycar

dia

Age

>75

yea

rsEl

ectro

card

iogr

amAn

gina

at

rest

with

tra

nsie

nt S

T T

wav

e in

vers

ions

> 0

.2 m

VN

orm

al o

r un

chan

ged

elec

troca

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gram

se

gmen

t ch

ange

s >

0.05

mV

Path

olog

ical

Q w

aves

durin

g an

epi

sode

of

ches

t di

scom

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Bun

dle

bran

ch b

lock

, ne

w o

r pr

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ewSu

stai

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vent

ricul

ar

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iac

mar

kers

Mar

kedl

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evat

ed (

e.g.

, tro

poni

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orSl

ight

ly e

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(e.g

., tro

poni

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.1 n

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: di

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and

man

agem

ent,

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kvill

e, M

d, 1

994,

Age

ncy

for

Hea

lth C

are

Polic

y an

d R

esea

rch

and

the

Nat

iona

l Hea

rt,

Lung

, an

d B

lood

Ins

titut

e, U

.S.

Publ

ic H

ealth

Ser

vice

, U

.S.

Dep

artm

ent

of H

ealth

and

Hum

an S

ervi

ces;

AH

CPR

Pub

licat

ion

No.

94-

0602

.C

AD

,co

rona

ry a

rter

y di

seas

e; M

I,m

yoca

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l inf

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*Est

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of t

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of

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A03748-ch008.qxd 2/7/06 9:33 PM Page 91

2. Aspirin. Platelet activation and aggregation play an important role in the pathophysiology of ACS. Aspirin inhibits the production ofthromboxane, which is a potent mediator of platelet activation. As soonas ACS is suspected, 325 mg of non–enteric-coated aspirin should be administered. Patients with aspirin allergy can be given clopidogrel.Ticlopidine should not be used in lieu of clopidogrel because of its slow(3 to 5 days) onset of action.

3. Beta-adrenergic blockers reduce myocardial oxygen demand by exertingnegative inotropic and chronotropic effects and protect against cardiacarrhythmias. Metoprolol is the preferred beta-adrenergic blocker becauseof its b1-selective activity. It is initially given as a 5-mg intravenous (IV)bolus. If tolerated, the 5-mg dose is repeated twice at 10-minuteintervals for a maximum dosage of 15 mg. The patient is then startedon orally administered metoprolol. The dosage is titrated to achieve amean systemic arterial pressure of 60 to 70 mmHg and a heart rate of60 beats/min. If these hemodynamic goals are not tolerated, the lowesttolerated mean arterial pressure and pulse should be targeted.

4. Nitrates reduce myocardial oxygen demand (by reducing preload) and increase myocardial blood flow (by dilating coronary vessels).Sublingual nitroglycerin tablets or spray should be used initially if thepatient is not hypotensive and has no other contraindications to theseagents, such as sildenafil use in the previous 24 hours. If the patient’schest discomfort does not resolve after three 0.4-mg nitroglycerintablets given 5 minutes apart, a continuous nitroglycerin IV infusion can be initiated at 10 µg/min and titrated upward by 10 µg every 3 to5 minutes until the patient’s discomfort resolves, the mean systemicarterial blood pressure drops below 25% of initial values in an initiallyhypertensive patient, or the systolic blood pressure drops below 110 mmHg in a normotensive patient. Common side effects includehypotension and headaches. Tachyphylaxis may occur with prolongeduse. A reflex tachycardia can also occur in patients not receiving a beta-adrenergic blocker or other negative chronotropic therapy.

5. Anticoagulation. Plaque rupture exposes tissue factor, which initiatesthe clotting cascade and coronary thrombosis. Patients with a non–STsegment elevation ACS should receive anticoagulation unless a major contraindication exists. Two forms of heparin are approved for use in these patients: unfractionated heparin and low–molecular-weight heparin. For the patient with a history of heparin-inducedthrombocytopenia who needs anticoagulation, lepirudin, a directthrombin inhibitor, can be administered as a 0.4-mg/kg bolus followedby a 0.15-mg/kg/hr (maximum 16.5 mg/hr) infusion with a targetedactivated partial thromboplastin time (aPTT) of 1.5 to 2.5 times theupper limit of normal.

a. Unfractionated heparin is initiated as an IV bolus followed by acontinuous infusion. The American Heart Association recommends a weight-based dosage regimen consisting of a 60- to 70-U/kg

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(maximum 5000-U) bolus followed by a maintenance infusion of 12 to15 U/kg/hr. The aPTT should be measured 6 hours after every dosageadjustment and the infusion adjusted to reach an aPTT of 2 to 2.5times the upper limit of normal. If the patient is receiving a GP IIb/IIIainhibitor, the target aPTT is lower (1.8 to 2 times the upper end ofnormal) in order to minimize the risk of bleeding.

b. Low–molecular-weight heparin is also approved for use in the patientwith a non–ST segment elevation ACS. Enoxaparin is administeredinitially as a 30-mg IV bolus, and then 1 mg/kg is administeredsubcutaneously twice daily. It has several advantages over heparin: It iseasier to administer, does not necessitate aPTT monitoring, and is lesslikely to cause heparin-induced thrombocytopenia. Conversely, it ismore expensive than heparin, it has a long half life, and its therapeuticeffects cannot be reversed completely with protamine. Thus concernshave been raised regarding its use in patients referred for coronaryrevascularization. The dosage is reduced in the patient with renal failureor obesity (weight > 120 kg), and the patient with a history of heparin-induced thrombocytopenia should not receive low–molecular-weightheparin.

c. Two double-blind randomized trials—Efficacy and Safety ofSubcutaneous Enoxaparin in Non–Q Wave Coronary Events (ESSENCE)and TIMI 11B—compared enoxaparin and unfractionated heparintherapy in 7081 patients with non–ST segment elevation ACS anddemonstrated a significant reduction in the incidence of MI and urgent revascularization for recurrent angina with enoxaparin.3,4 In these studies, patients were referred for catheterization if they hadspontaneous or provocable ischemia (known as an ischemia-guidedmanagement strategy). The recent Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors(SYNERGY) study compared low–molecular-weight heparin andunfractionated heparin therapy in 10,027 patients with non–STsegment elevation ACS who were treated with a GP IIb/IIIa inhibitor andan early invasive strategy.5 The primary endpoint (incidence of death orMI at 30 days) was similar for the two treatments; however, patientsreceiving low–molecular-weight heparin had a higher rate of bleeding.

6. Clopidogrel is a thienopyridine antiplatelet agent that inhibits adenosinediphosphate–mediated activation of platelets. Clopidogrel has a quickonset of action when administered as a loading dose, and its benefits in non–ST segment elevation ACS have been demonstrated in severallarge-scale trials.

a. In the Clopidogrel in Unstable Angina to Prevent Recurrent IschemicEvents (CURE) trial, 12,562 patients with ACS were randomized toreceive placebo or clopidogrel, 300 mg loading dose and then 75 mgdaily.6 All participants received daily aspirin and were followed for 3 to12 months. The clopidogrel-treated patients were less likely to suffer amajor adverse cardiovascular event (9.4% vs. 11.3%) but more likely


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to have major bleeding (3.7% vs. 2.7%, p = .001). Those whoreceived clopidogrel within 5 days of coronary artery bypass surgeryhad a significantly higher risk of bleeding and need for transfusionsperioperatively. For this reason, many surgeons delay cardiac surgery if the patient has received clopidogrel within 5 days of the plannedprocedure.

b. Two other studies address the use of clopidogrel in the setting of PCIand revascularization: the PCI CURE study7 and the Clopidogrel for theReduction of Events During Observation (CREDO) study.8 The PCICURE study, a subset of the CURE trial, evaluated the 2658 patientsundergoing PCI who were pretreated with clopidogrel and receivedstudy drug or placebo for 4 weeks after the procedure. Compared withthose in the placebo group, the clopidogrel-treated patients experienceda lower rate of the combined endpoint of cardiovascular death, MI, orurgent revascularization at 30 days (6.4% and 4.5%, respectively; p = .03). The CREDO trial randomly assigned 2116 patients toplacebo or clopidogrel 3 to 24 hours before PCI and for up to 12months afterward. The clopidogrel-treated patients were less likely tohave an adverse ischemic event in the year after PCI. Thus prolongedtherapy with clopidogrel after successful PCI reduces the risk ofsubsequent ischemic events.

c. Current American College of Cardiology and American Heart Association(ACC/AHA) recommendations for the use of clopidogrel include allpatients not at high risk for bleeding in whom a noninterventionalapproach is planned. A 300-mg oral dose is administered initially, andthen 75 mg is given daily for at least 1 month. Clopidogrel should also be used in patients in whom PCI is planned.9 In these patients, a300- to 600-mg oral loading dose should be given 4 to 6 hours beforethe procedure and 75 mg administered daily for up to 12 monthsafterward. Because clopidogrel therapy should be discontinued at least5 to 7 days before elective coronary artery bypass grafting, manycardiologists avoid giving clopidogrel to the patient with ACS in whomcardiac catheterization and a determination regarding the need forcoronary artery bypass grafting can be performed expeditiously (within24 to 36 hours of presentation).

7. Glycoprotein IIb/IIIa receptor inhibitors. The final pathway in plateletaggregation is activation of the GP IIb/IIIa receptor, which allowsplatelets to bind to fibrinogen and von Willebrand factor. Three GPIIb/IIIa inhibitors are available: abciximab, a monoclonal antibodyagainst the IIb/IIIa receptor; tirofiban, a peptidomimetic inhibitor; andeptifibatide, a cyclic peptide inhibitor. Several studies have shown theclinical efficacy of eptifibatide and tirofiban in the setting of ACS.10-12

Subgroup analysis of the data in these studies shows that the greatestclinical benefit occurs in high- and intermediate-risk patients. Currentdata support the use of eptifibatide or tirofiban in high-risk patients,especially those with an elevated serum troponin in whom coronary

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angiography is likely. An IV bolus of eptifibatide or tirofiban is followedby continuous IV infusion of the drug for 48 to 72 hours. If PCI isperformed, the infusion is continued for 12 to 24 hours after theprocedure. Abciximab is beneficial only in patients undergoing PCI,13 inwhich case the IV infusion is initiated in the cardiac catheterizationlaboratory and continued for 12 hours after PCI.

8. Early percutaneous coronary angiography compared with an ischemia-guided approach. Three randomized, prospective studies have shownthat an early invasive strategy in conjunction with aggressive medicalmanagement is superior to an ischemia-guided approach, in whichangiography and PCI are reserved for patients with spontaneous orprovocable ischemia.14-16 Subgroup analysis has shown that high- andintermediate-risk patients benefit the most from an early invasivestrategy. The current ACC/AHA recommendations include an earlyinvasive strategy for any patient with high-risk features (Box 8-2). Forintermediate- and low-risk patients without evidence of myocardialnecrosis (elevation in cardiac biomarkers) a noninvasive stress test is areasonable approach, with catheterization reserved for those withinducible ischemia. For patients with evidence of myocardial necrosis,most cardiologists would recommend early cardiac catheterization.

IV. MANAGEMENT: ST SEGMENT ELEVATION ACSA. RISK STRATIFICATION1. As with all forms of ACS, risk stratification is crucial to patient

management. A classification scheme developed in the late 1960s by

BOX 8-2CLASS I RECOMMENDATIONS FOR AN EARLY INVASIVE STRATEGY FOR UNSTABLE ANGINA AND NON–ST SEGMENT ELEVATION MYOCARDIAL INFARCTIONRecurrent angina or ischemia at rest or with low-level activities despite intensive

antiischemic therapyElevated troponin T or troponin INew or presumably new ST segment depressionRecurrent angina or ischemia with congestive heart failure symptoms, S3 gallop,

pulmonary edema, worsening rales, or new mitral regurgitationHigh-risk findings on noninvasive stress testingDepressed left ventricular systolic function (e.g., ejection fraction < 0.4 on

noninvasive testing)Hemodynamic instabilitySustained ventricular tachycardiaPercutaneous coronary intervention within 6 moPrior coronary artery bypass graft

Modified from Braunwald E et al: Circulation 106:1893, 2002.

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Killip and Kimball correlates heart failure signs and outcome17

(Table 8-3). Many studies have confirmed that the Killip classificationpredicts short- and long-term mortality after MI.

2. The TIMI study group developed a simple bedside stratification tool forpatients with ST segment elevation ACS18 (Table 8-4), assigning pointsfor clinical risk indicators on the basis of patient history, physicalexamination, and features on presentation. When applied to the 84,029patients in the National Registry of Myocardial Infarction 3 database,the scoring system reveals a graded risk in 30-day mortality rangingfrom 1.1% to 30% for scores ranging from 0 to more than 8,respectively.19

TABLE 8-3RISK STRATIFICATION BASED ON KILLIP CLASS IN THE GISSI-1 TRIAL OFSTREPTOKINASE AND PLACEBO IN ACUTE MYOCARDIAL INFARCTION

GISSI-1 (% of patients)Killip Class Definition Incidence Control Mortality Lytic MortalityI No congestive 71 7.3 5.9

heart failureII S3 gallop or 23 19.9 16.1

basilar ralesIII Pulmonary edema 4 39 33

(rales more than halfway up)

IV Cardiogenic shock 2 70.1 69.9(systolic blood pressure <90)

TABLE 8-4THROMBOLYSIS IN MYOCARDIAL INFARCTION RISK SCORE FOR ST SEGMENTELEVATION MYOCARDIAL INFARCTIONClinical Risk Indicators PointsHISTORYAge ≥75 yr 3Age 65-74 yr 2History of diabetes, hypertension, or angina 1EXAMINATIONSystolic blood pressure < 100 mmHg 3Heart rate >100 beats/min 2Killip class II-IV 2Weight < 67 kg 1PRESENTATIONAnterior ST elevation or left bundle branch block 1Time to reperfusion > 4 hr 1Total possible points 14Data from Morrow DA et al: JAMA 286:1356, 2001.

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B. INTERVENTION: PHARMACOLOGIC AND NONPHARMACOLOGIC1. Patients should be treated with an antiischemic drug regimen consisting

of aspirin, beta-blockers, and nitroglycerin and considered for acutereperfusion therapy via administration of a thrombolytic agent orprimary PCI. Early flow restoration in the infarct-related artery salvagesmyocardium and improves survival. The adequacy of coronary bloodflow after reperfusion therapy can be assessed angiographically usingthe TIMI grading system (Table 8-5).

2. Early recognition of ischemia and rapid reperfusion salvagemyocardium and improve survival. Initiation of thrombolytic therapywithin 30 minutes of symptom onset can abort infarction. Althoughpatients derive survival benefit if treated with a thrombolytic agentwithin 12 hours of symptom onset,24 maximum benefit is obtained if athrombolytic agent is administered within 2 hours of symptom onset.20

With primary PCI, mortality rates increase significantly when door-to-balloon time exceeds 90 minutes.21 Based on these data, currentACC/AHA recommendations are to administer thrombolytic therapywithin 30 minutes or perform PCI within 90 minutes of arrival, with anoverall goal of total ischemic time (from symptom onset to intervention)less than 120 minutes.22

3. Thrombolytics (fibrinolytic agents) act by converting plasminogen toplasmin, which digests fibrin and enhances thrombus dissolution. Large randomized controlled trials have demonstrated relative mortalitybenefits on the order of 20% to 30% when thrombolytic therapy isadministered in a timely manner.

a. Multiple thrombolytic agents are available in the United States. Whenchoosing an agent, one must consider factors such as efficacy, sideeffect profile, ease of administration, and cost. Several of the majorthrombolysis trials are reviewed in Table 8-6.

b. Before a thrombolytic agent is administered, the patient must bescreened for potential contraindications that increase the risk ofintracranial hemorrhage and bleeding (Box 8-3).

TABLE 8-5TIMI ANGIOGRAPHIC GRADING SYSTEM: ANGIOGRAPHIC ASSESSMENT OFRESTORATION OF FLOW TO THE IRATIMI Grade Definition0 Complete occlusion of the IRA1 Some flow beyond the obstruction but none distally (e.g., penetration

of blood without perfusion)2 Reperfusion of the entire IRA but flow is delayed and slower than

normal3 Normal flow in the IRAModified from TIMI Study Group: N Engl J Med 312:932, 1985.IRA, infarct-related artery; TIMI, Thrombolysis in Myocardial Infarction.

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c. Efficacy of thrombolytic therapy. Patients with complete resolution ofST segment elevation at 90 minutes have a 93% likelihood of infarct-related artery patency and a nearly 80% probability of TIMI 3 flow.27

Patients (approximately 20% to 30% of those receiving thrombolyticagents) who do not have improvement or resolution of chest discomfortor at least a 50% reduction in the degree of ST elevation within 60 minutes of thrombolytic administration should be considered forimmediate coronary angiography.28

d. Current recommendations of the ACC and AHA regarding thrombolytictherapy are shown in Box 8-4.29

4. PCI. Primary PCI requires the immediate availability of a catheterizationlaboratory and skilled staff. High-volume (49 or more procedures peryear) and intermediate-volume (17 to 48 procedures per year) centershave lower mortality rates than low-volume centers.30 Despite theselimitations, primary PCI is the preferred therapy for ST segmentelevation MI when performed in a timely fashion and by skilledpractitioners. Thrombolytic therapy restores normal blood flow to theinfarct-related artery in 50% to 60% of patients,31 and primary PCIdoes so in more than 90%.32 A meta-analysis of 23 trials showedbetter outcomes for PCI than for thrombolytic therapy, with lower ratesof short-term death (7% vs. 9%, p = .0004), nonfatal reinfarction (3% vs. 7%, p < .0001), stroke (1% vs. 2%, p = .0004), and the

TABLE 8-6SELECT THROMBOLYTIC STUDIESStudy Year FindingsISIS-2 1988 This placebo-controlled, randomized trial of 17,187 patients

demonstrated lower 30-day mortality with streptokinase(9.2%) or aspirin (9.4%) treatment than placebo (13.2%) (p < .00001) and lowest mortality when aspirin andstreptokinase were combined (8%) (p < .00001).23

GUSTO-1 1993 In this 41,021 patient study, patients treated with t-PA andintravenous heparin had higher coronary patency rates andbetter 30-day survival (6.4%) than patients treated withstreptokinase and subcutaneous or intravenous heparin(7.4%) or a combination of reduced-dose t-PA andstreptokinase (7.2%).24

GUSTO-3 1997 This trial of 15,059 patients compared reteplase withalteplase. The 30-day mortality rates were similar for the twogroups, as were the nonfatal stroke rates.25

ASSENT-2 1999 This trial of 16,949 patients compared tenecteplase andalteplase. Mortality at 30 days was equivalent (6.18% vs.6.15%, respectively); however, the tenecteplase-treated grouphad fewer noncerebral bleeding events (26.4% vs. 28.9%, p = .0003) and transfusions (4.2% vs. 5.5%, p = .0002).26

t-PA, tissue plasminogen activator.

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BOX 8-4RECOMMENDATIONS OF THE AMERICAN COLLEGE OF CARDIOLOGY ANDAMERICAN HEART ASSOCIATION FOR THROMBOLYTIC THERAPYCLASS IST elevation (>0.1 mm in 2 or more contiguous leads), time to therapy £12 hrNew or presumably new left bundle branch block within past 12 hrCLASS IIA12-lead electrocardiographic findings consistent with a true posterior MI within

12 hr of symptom onsetPatients with symptoms beginning within the past 12 to 24 hr with continued ST

elevation (>0.1 mm in 2 or more contiguous leads) and ischemic symptomsCLASS IIIST elevation with time to therapy >24 hrST segment depression unless true posterior MI suspected

Data from Antman EM et al: Circulation 110:588-636, 2004. Available at www.acc.org.MI, myocardial infarction.

BOX 8-3ABSOLUTE AND RELATIVE CONTRAINDICATIONS TO THROMBOLYTICTHERAPY FOR MYOCARDIAL INFARCTIONABSOLUTE CONTRAINDICATIONS

Any prior intracranial hemorrhageKnown structural cerebral vascular lesion (e.g., arteriovenous malformation)Known malignant intracranial neoplasm (primary or metastatic)Ischemic stroke within 3 mo except acute ischemic stroke within 3 hrSuspected aortic dissectionActive bleeding or bleeding diathesis (excluding menses)Significant closed head or facial trauma within 3 moRELATIVE CONTRAINDICATIONS

History of chronic, severe, poorly controlled hypertensionSevere uncontrolled hypertension on presentation (>180/110 mmHg)History of prior ischemic stroke > 3 mo before, dementia, or known intracranial

disorder not covered in contraindicationsTraumatic or prolonged (> 10 min) cardiopulmonary resuscitation or major surgery

(within 3 wk)Noncompressible vascular puncturesInternal bleeding within 4 weeksFor streptokinase or anistreplase, prior exposure (especially within 2 yr) or prior

allergic reactionPregnancyActive peptic ulcerCurrent use of anticoagulants (the higher the international normalized ratio, the

higher the risk of bleeding)

Modified from Antman EM et al: Circulation 110:588-636, 2004. Available at www.acc.org.

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combined endpoint of death, nonfatal reinfarction, and stroke (8% vs.14%, p < .0001).33 Primary PCI is also associated with a significantlylower rate of long-term (5-year) mortality than streptokinase (13% vs.24%, p = .01).34

a. Transport to PCI sites. Recognition of the advantages of PCI overthrombolytics has led investigators to explore whether the patient withacute MI who presents to a hospital without catheterization facilitiesshould be transferred emergently to a site where PCI is available. If thetriage and transport time is short (�90 minutes), then transfer of thepatient to a center with catheterization facilities may be preferable. Inthe recent Danish Trial in Acute Myocardial Infarction (DANAMI-2)study, patients treated in this manner had a lower incidence ofreinfarction than patients treated with thrombolysis.35 A recentmetaanalysis of 21 studies comparing PCI with thrombolytic therapyshowed equivalence of the two reperfusion strategies with respect to30-day mortality when the delay to PCI was 62 minutes or more andequivalence for the two strategies for composite endpoints of death,reinfarction, or stroke when the delay to PCI was 93 minutes or more.36

Thus for institutions where timely administration of PCI is not practical,thrombolytics remain the treatment of choice for ST segment elevationACS.

b. Current ACC/AHA recommendations for primary PCI are summarized inBox 8-5.

5. GP IIb/IIIa receptor inhibitors. The role of GP IIb/IIIa receptor inhibitorsin ST segment elevation ACS is still being defined.

a. Many believe that administration of a GP IIb/IIIa receptor inhibitor in conjunction with reduced-dose thrombolytic therapy provides more complete macrovascular and microvascular reperfusion thanthrombolytic monotherapy. Several small trials in which a thrombolyticagent and GP IIb/IIIa receptor inhibitor were given concomitantlyshowed improvements in early angiographic IRA patency and STsegment resolution.37-39 Larger trials, such as ASSENT 3 (tenecteplaseplus abciximab vs. tenecteplase)40 and Global Use of Strategies to OpenOccluded Arteries (GUSTO) V (reteplase plus abciximab vs. reteplase),41

have shown that survival after therapy with a GP IIb/IIIa inhibitor andthrombolytic agent is no different than after a thrombolytic agent is given alone. However, the combination is associated with a higherincidence of bleeding complications and intracranial hemorrhage,particularly in older adults. Therefore combination therapy is notjustified at this time.

b. When coupled with primary PCI, GP IIb/IIIa receptor inhibition reduces the composite endpoint of death, MI, and the need for urgentrevascularization. The ADMIRAL trial (n = 300) demonstrated asignificant reduction in the combined endpoint of death, reinfarction,and need for urgent repeat revascularization with abciximab in patients undergoing PCI for ST segment elevation ACS (6.0% vs.

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BOX 8-5RECOMMENDATIONS FOR PRIMARY PCICLASS IAs an alternative to thrombolytic therapy in patients with acute MI and ST segment

elevation or new or presumed new LBBB who can undergo angioplasty of theinfarct-related artery within 12 hr of onset of symptoms if performed in a timelyfashion (balloon inflation within 90 min of presentation) by people skilled in theprocedure and supported by experienced personnel in an appropriate laboratoryenvironment.

Specific ConsiderationsPCI should be performed as quickly as possible, with a DTBT goal <90 min.If symptom duration is <3 hr and the expected DTBT minus door-to-needle time is

<1 hr, PCI is preferred; if DTBT minus door-to-needle time is >1 hr, fibrinolytictherapy is preferred.

If symptom duration is >3 hr, PCI is preferred, with goal DTBT <90 min.PCI should be considered, if clinically suitable, for patients <75 yr old with STEMI

or LBBB who develop shock within 36 hr of MI and can be revascularizedwithin 18 hr of shock.

PCI should be performed in patients with severe CHF or pulmonary edema (Killipclass III) and onset of symptoms within 12 hr, with DTBT as short as possible(i.e., goal <90 min).

CLASS IIAPCI is reasonable for patients with good functional status who are 75 yr or older

with STEMI or LBBB or who develop shock within 36 hr of MI and are suitablefor revascularization that can be performed within 18 hr of shock.

It is reasonable to perform PCI with symptom onset in the past 12-24 hours whenCHF or hemodynamic or electrical instability is present.

CLASS IIBThe benefit of primary PCI for patients with STEMI who are eligible for fibrinolysis

is not well established when performed by operators with fewer than 75 PCIprocedures per year.

CLASS IIIPCI should not be performed in a noninfarcted artery at the time of primary PCI in

patients without hemodynamic compromise.Primary PCI should not be performed in asymptomatic patients more than 12 hr

after onset of STEMI if they are hemodynamically and electrically stable.

Data from Antman EM et al: Circulation 110:588-636, 2004. Available at www.acc.org.CHF, congestive heart failure; DTBT, door-to-balloon time; LBBB, left bundle branch block; MI,myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST segment elevationmyocardial infarction.

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14.6%, p = .01).42 The largest study of GP IIb/IIIa receptor inhibitionduring primary PCI for ST segment elevation ACS, the CADILLAC study,enrolled 2082 patients and demonstrated a significant benefit whenabciximab was used with PCI (with or without stenting). Major adverseevents occurred in 20% of patients in the primary PCI group, 16.5%with primary PCI plus abciximab, 11.5% with stenting alone, and10.2% with stenting plus abciximab (p < .001). The majority of benefitseen with abciximab plus stenting was related to a lower risk of repeatrevascularization procedures.43 Nonetheless, as interventional techniquesevolve, GP IIb/IIIa receptor inhibitors continue to demonstrate consistentbenefits for patients treated with PCI reperfusion.

V. POST-ACS TREATMENTA. COMPLICATIONSApproximately 80% of in-hospital deaths after ST segment elevation ACSare caused by severe left ventricular pump failure. The remaining 20% of in-hospital deaths are caused by post-MI mechanical complications(Table 8-7), including mitral regurgitation from a ruptured papillarymuscle, left ventricular free wall rupture, and acute ventricular septaldefect.44 Prompt clinical evaluation and bedside echocardiography of thepatient with circulatory collapse are important in establishing the diagnosisand directing therapy.

Reperfusion arrhythmias are common after antegrade blood flow issuccessfully reestablished in the IRA. Premature ventricular contractions,nonsustained ventricular tachycardia, accelerated idioventricular rhythm,and heart block are common after successful reperfusion. In addition, thepatient with an inferior infarct may have sinus bradycardia and transienthypotension (Bezold-Jarisch reflex).B. SECONDARY PREVENTIONOnce stabilized, patients with ACS should undergo risk factor assessmentfollowed by the initiation of medications and lifestyle interventions for

TABLE 8-7COMPLICATIONS OF MI

Percentage of Time to Onset MI-Associated

Incidence (%) After MI MortalityPapillary rupture causing

severe mitral regurgitation <1 2-7 d 5Left ventricular rupture 2 5-14 d 10Acute ventricular septal defect 7 Any time 5Severe left ventricular

dysfunction and shock Any time 80Modified from Reeder GS: Mayo Clin Proc 70:880, 1995.MI, myocardial infarction.

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secondary prevention. Numerous studies document that medical therapiesfor secondary prevention of coronary artery disease remain underused and that practice patterns vary throughout the United States.45,46 Initiationof secondary prevention techniques should occur before discharge tomaximize patient compliance and to ensure that the patient is on anappropriate treatment regimen. Risk factor modification should includesmoking cessation and dietary counseling. Patients should be encouragedto increase the amount of weekly exercise and to lose weight if necessary.Diabetic patients should maintain tight glucose control. Secondaryprevention medications, including angiotensin-converting enzymeinhibitors, beta-blockers, aspirin, and lipid-lowering agents, should also be initiated.PEARLS AND PITFALLS� Non–ST segment elevation ACS encompasses the two prior terms

unstable angina and non–Q wave MI.� In the patient with ST segment elevation ACS, rapid reperfusion

(via primary PCI or thrombolytic therapy) salvages myocardium andimproves survival. This requires rapid assessment (including 12-leadelectrocardiography), triage, and risk assessment.

� At presentation, the patient with ACS should be questioned about ahistory of cocaine or sildenafil use.

� Patients with heparin allergy or heparin-induced thrombocytopenia who need anticoagulation should be given lepirudin or another directthrombin inhibitor.

� b1-selective beta-adrenergic blockers can be used safely in the patientwith a history of mild to moderate obstructive pulmonary disease.47

REFERENCES1. American Heart Association: Heart disease and stroke statistics: 2004 update.

Dallas, Tex, 2003, American Heart Association. D2. Antman E et al: The TIMI risk score for unstable angina/non-ST elevation MI: a

method for prognostication and therapeutic decision making, JAMA 284:835,2000. B

3. Cohen M et al: A comparison of low-molecular weight heparin withunfractionated heparin for unstable coronary disease, N Engl J Med 337:447,1997. A

4. Antman E et al: Enoxaparin prevents death and cardiac ischemic events inunstable angina/non-Q wave myocardial infarction, Circulation 100:1593, 1999. D

5. Ferguson JJ et al, SYNERGY Trial Investigators: Enoxaparin vs. heparin in high-risk patients with non–ST-segment elevation acute coronary syndromes managedwith an intended early invasive strategy: primary results of the SYNERGYrandomized trial, JAMA 292:45-54, 2004. A

6. Mehta SR, Yusuf S, Peters RJG et al for the Clopidogrel in Unstable Angina toPrevent Recurrent Events (CURE) Trial Investigators: The Clopidogrel in UnstableAngina to Prevent Recurrent Events (CURE) trial, N Engl J Med 345:494, 2001. A


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7. Mehta SR, Yusuf S, Peters RJG et al, for the Clopidogrel in Unstable Angina toPrevent Recurrent Events (CURE) Trial Investigators: Effects of pretreatment withclopidogrel and aspirin followed by long-term therapy in patients undergoingpercutaneous coronary intervention: the PCI-CURE study, Lancet 358:527,2001. A

8. Steinhubl SR, Berger PB et al, for the CREDO Investigators: Early and sustaineddual oral antiplatelet therapy following percutaneous coronary intervention: arandomized controlled trial, JAMA 288:2411, 2002. A

9. ACC/AHA 2002 guideline update for the management of patients with unstableangina and non–ST-segment elevation myocardial infarction, available atwww.americanheart.org. D

10. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) StudyInvestigators: A comparison of aspirin plus tirofiban with aspirin plus heparin forunstable angina, N Engl J Med 338:1498, 1998. A

11. PRISM-PLUS Investigators: Inhibition of the platelet glycoprotein IIb/IIIa receptorwith tirofiban in unstable angina and non–Q-wave myocardial infarction, N Engl JMed 338:1488, 1998. A

12. PURSUIT Investigators: Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes, N Engl J Med 339:436,1998. A

13. Simoons M: Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcomein patients with acute coronary syndromes without early coronaryrevascularisation: the GUSTO IV–ACS randomised trial, Lancet 357:1915, 2001. A

14. Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease(FRISC II) Investigators: Invasive compared with non-invasive treatment inunstable coronary-artery disease: FRISC II prospective randomised multicentrestudy, Lancet 354:708, 1999. A

15. Cannon C et al: Tactics: TIMI 18, N Engl J Med 344:1879, 2001. A16. Fox KAA et al: Interventional versus conservative treatment for patients with

unstable angina or non–ST-elevation myocardial infarction: the British HeartFoundation RITA 3 randomised trial, Lancet 360:743, 2002. A

17. Killip T, Kimball JT: Treatment of myocardial infarction in a coronary care unit,Am J Cardiol 20:457, 1967. B

18. Morrow DA et al: TIMI risk score for ST-elevation myocardial infarction: aconvenient, bedside, clinical score for risk assessment at presentation: an InTIMEII trial substudy, Circulation 102:2031, 2000. B

19. Morrow DA et al: Application of the TIMI risk score for ST-elevation MI in theNational Registry of Myocardial Infarction 3, JAMA 286:1356, 2001. B

20. Boersma E et al: Early thrombolytic treatment in acute myocardial infarction:reappraisal of the golden hour, Lancet 348:771, 1996. D

21. Cannon CP et al: Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acutemyocardial infarction, JAMA 283:2941, 2000. B

22. Antman EM et al: ACC/AHA guidelines for management of patients with acutemyocardial infarction. A report of the American College of Cardiology/AmericanHeart Association Task Force on Practice Guidelines (Writing Committee to Revisethe 1999 Guidelines for Management of Patients with Acute MyocardialInfarction), 2004, available at www.acc.org. D

23. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group:Randomised trial of intravenous streptokinase, oral aspirin, both, or neither

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among 171,817 cases of suspected acute myocardial infarction: ISIS-2, Lancet2:349, 1988. A

24. GUSTO Investigators: An international randomized trial comparing fourthrombolytic strategies for acute myocardial infarction, N Engl J Med 329:673,1993. A

25. A comparison of reteplase with alteplase for acute myocardial infarction. TheGlobal Use of Strategies to Open Occluded Arteries (GUSTO III) Investigators, NEngl J Med 337:1118, 1997. A

26. Single-bolus tenecteplase compared with front-loaded alteplase in acutemyocardial infarction: the ASSENT-2 double blind randomized trial, Lancet354:716, 1999. A

27. de Lemos JA, Braunwald E: ST segment resolution as a tool for assessing theefficacy of reperfusion therapy, J Am Coll Cardiol 38:1283, 2001. C

28. Fernandez AR et al: ST segment tracking for rapid determination of patency ofthe infarct-related artery in acute myocardial infarction, J Am Coll Cardiol26:675, 1995. B

29. Antman EM et al: ACC/AHA guidelines for management of patients with ST-elevation myocardial infarction: executive summary. A report of the AmericanCollege of Cardiology/American Heart Association Task Force on PracticeGuidelines (Committee to Revise the 1999 Guidelines for Management ofPatients with Acute Myocardial Infarction), Circulation 110:588-636, 2004,available at www.acc.org. D

30. Magid DJ et al: Relation between hospital primary angioplasty volume andmortality for patients with acute MI treated with primary angioplasty vsthrombolytic therapy, JAMA 284:3131, 2000. B

31. The GUSTO Investigators: The effects of tissue plasminogen activator,streptokinase, or both on coronary-artery patency, ventricular function, andsurvival after acute myocardial infarction, N Engl J Med 329:1615, 1993. A

32. Henning RA et al: A comparison of coronary angioplasty with fibrinolytic therapyin acute myocardial infarction, N Engl J Med 349:733, 2003. A

33. Keeley EC et al: Primary angioplasty versus intravenous thrombolytic therapy foracute myocardial infarction: a quantitative review of 23 randomised trials, Lancet361:13-20, 2003. C

34. Zijlstra F et al: Long-term benefit of primary angioplasty as compared tothrombolytic therapy for acute myocardial infarction, N Engl J Med 341:1431,1999. B

35. Anderson HZ et al. DANAMI-2 Investigators. A comparison of acute coronaryangioplasty with fibrinolytic therapy in acute myocardial infarction, N Engl J Med349(18):733-747, 2003. A

36. Nallamothu BK, Bates ER: Percutaneous coronary intervention versus fibrinolytictherapy in acute myocardial infarction: is timing (almost) everything? Am JCardiol 92:824, 2003. D

37. Kleiman NS et al: Profound inhibition of platelet aggregation with monoclonalantibody 7E3 Fab after thrombolytic therapy: results of the Thrombolysis andAngioplasty in Myocardial Infarction (TAMI)-8 pilot study, J Am Coll Cardiol22:381, 1993. B

38. de Lemos J et al: Abciximab improves both epicardial flow and myocardialreperfusion in ST-elevation myocardial infarction: observations from the TIMI 14trial, Circulation 101:239, 2000. B

39. Strategies for Patency Enhancement in the Emergency Department (SPEED)Group: Trial of abciximab with and without low dose reteplase for acutemyocardial infarction, Circulation 100:2788, 2000. B


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40. ASSENT-3 Investigators: Efficacy and safety of tenecteplase in combination withenoxaparin, abciximab, or unfractionated heparin: the ASSENT 3 randomised trialin acute myocardial infarction, Lancet 358:605, 2001. A

41. GUSTO-V Investigators: Reperfusion therapy for acute myocardial infarction withfibrinolytic therapy or combination reduced fibrinolytic therapy and plateletglycoprotein IIb/IIIa inhibition: the GUSTO-V randomised trial, Lancet 357:1905,2001. A

42. Montalescot G et al: Abciximab before direct angioplasty and stenting inmyocardial infarction regarding acute and long-term follow-up, N Engl J Med344:1895, 2001. B

43. Stone GW et al: Comparison of angioplasty with stenting, with or withoutabciximab, in acute myocardial infarction, N Engl J Med 346:957, 2002. A

44. Reeder GS: Identification and treatment of complications of myocardial infarction,Mayo Clin Proc 70:880, 1995. B

45. O’Connor GT et al: Geographic variation in the treatment of acute myocardialinfarction, JAMA 281:627, 1999. B

46. Stafford RS, DC Radley: The underutilization of cardiac medications of provenbenefit, 1990 to 2002, J Am Coll Cardiol 41:56, 2003. B

47. Salpeter SR et al: Cardioselective b-blockers in patients with reactive airwaydisease: a meta-analysis, Ann Intern Med 137:715, 2002. C

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