Acute Coronary Syndrome_eMedicine

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Acute Coronary Syndrome

Last Updated: March 27, 2006

Synonyms and related keywords:ACS, angina, myocardial ischemia, acute myocardialischemia, myocardial infarction, MI, coronary artery disease, coronary heart disease, heart

disease, chest pain, atherosclerotic plaques, variant angina, Prinzmetal angina, coronaryvasospasm, stable angina, unstable angina, hypertension, diabetes mellitus, smoking,

hypercholesterolemia, hyperlipidemia

AUTHOR INFORMATION Section 1 of 10

Author Information Introduction Clinical Differentials Workup TreatmentMedicationFollow-upMiscellaneousBibliography

Author: Drew E. Fenton, MD, Emergency Physician, Department of Emergency

Medicine, St. Mary Medical Center

Coauthor(s):Brigitte M Baumann, MD, DTM & H, Assistant Professor, Head, Division

of Research, Department of Emergency Medicine, University of Medicine and Dentistryof New Jersey, Robert Wood Johnson Medical School; Sarah Stahmer, MD, Residency

Director, Associate Professor, Department of Emergency Medicine, University of

Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School

Drew E. Fenton, MD, is a member of the following medical societies: American Academy

of Emergency Medicine

Editor(s): Edward Bessman, MD, Chairman, Department of Emergency Medicine, JohnHopkins Bayview Medical Center; Assistant Professor, Department of Emergency

Medicine, Johns Hopkins University; Francisco Talavera, PharmD, PhD, Senior

Pharmacy Editor, eMedicine; Gary Setnik, MD, Chair, Department of Emergency

Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine,

Harvard Medical School; John Halamka, MD, Chief Information Officer, CareGroupHealthcare System, Assistant Professor of Medicine, Department of Emergency Medicine,

Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard MedicalSchool; and Jonathan Adler, MD, Attending Physician, Department of Emergency

Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard

Medical School

Disclosure

INTRODUCTION Section 2 of 10

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Background: The initial diagnosis of acute coronary syndrome (ACS) may be based

entirely on history, risk factors, and, to a lesser extent, ECG findings. The symptoms are

due to myocardial ischemia, the underlying cause of which is an imbalance betweensupply and demand of myocardial oxygen.

Patients with ACS include those whose clinical presentations cover the following rangeof diagnoses: unstable angina, nonST-elevation myocardial infarction (NSTEMI), and

ST-elevation myocardial infarction (STEMI). This ACS spectrum concept is a usefulframework for developing therapeutic strategies.

Pathophysiology: Myocardial ischemia is most often due to atherosclerotic plaques,

which reduce the blood supply to a portion of myocardium. Initially, the plaques allow

sufficient blood flow to match myocardial demand. When myocardial demand increases,the areas of narrowing may become clinically significant and precipitate angina. Angina

that is reproduced by exercise, eating, and/or stress and is subsequently relieved with rest,

and without recent change in frequency or severity of activity that produce symptoms, is

called chronic stable angina. Over time, the plaques may thicken and rupture, exposing athrombogenic surface upon which platelets aggregate and thrombus forms. The patient

may note a change in symptoms of cardiac ischemia with a change in severity or ofduration of symptoms. This condition is referred to as unstable angina.

Patients with STEMI have a high likelihood of a coronary thrombus occluding the infarct

artery. Angiographic evidence of coronary thrombus formation may be seen in more than

90% of patients with STEMI but in only 1% of patients with stable angina and about 35-75% of patients with unstable angina or NSTEMI. However, not every STEMI evolves

into a Q-wave MI; likewise, a patient with NSTEMI may develop Q waves.

The excessive mortality rate of coronary heart disease is primarily due to rupture andthrombosis of the atherosclerotic plaque. Inflammation plays a critical role in plaquedestabilization and is widespread in the coronary and remote vascular beds. Systemic

inflammatory, thrombotic, and hemodynamic factors are relevant to the outcome.

Evidence indicates that platelets contribute to promoting plaque inflammation as well asthrombosis. A new theory of unbalanced cytokine-mediated inflammation is emerging,

providing an opportunity for intervention.

A less common cause of angina is dynamic obstruction, which may be caused by intense

focal spasm of a segment of an epicardial artery (Prinzmetal angina). Coronaryvasospasm is a frequent complication in patients with connective tissue disease. Other

causes include arterial inflammation and secondary unstable angina. Arterial

inflammation may be caused by or related to infection. Secondary unstable angina occurswhen the precipitating cause is extrinsic to the coronary arterial bed, such as fever,

tachycardia, thyrotoxicosis, hypotension, anemia, or hypoxemia. Most patients who

experience secondary unstable angina have chronic stable angina as a baseline medical

condition.


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Spontaneous and cocaine-related coronary artery dissection remains an unusual cause of

ACS and should be included in the differential diagnosis, especially when a younger

female or cocaine user is being evaluated. An early clinical suspicion of this disease isnecessary for a good outcome. Cardiology consultation should be obtained for

consideration for urgent percutaneous coronary intervention.

Although rare, pediatric and adult ACS may result from the following (see Myocardial

Infarction in Childhood):

ACS may occur with Marfan syndrome; Kawasaki disease; Takayasu arteritis; or

cystic medial necrosis with aortic root dilatation, aneurysm formation, and

dissection into the coronary artery.

Anomalous origin of the left coronary artery from the pulmonary artery mayoccur as unexplained sudden death in a neonate.

Coronary artery ostial stenosis may occur after repair of a transposition of the

great arteries in the neonatal period.

An aberrant left main coronary artery with its origin at the right sinus of Valsalvamay cause ACS, especially with exertion.

Traumatic myocardial infarction can occur in patients at any age.

Accelerated atherosclerosis is known to occur in cardiac transplant recipients on

immunosuppressive therapy.

Progeria

Irrespective of the cause of unstable angina, the result of persistent ischemia ismyocardial infarction (MI).

Frequency:

In the US: Although the exact incidence of ACS is difficult to ascertain, hospital

discharge data indicate that 1,680,000 unique discharges for ACS occurred in2001.

Internationally: In Britain, annual incidence of angina is estimated at 1.1 cases

per 1000 males and 0.5 cases per 1000 females aged 31-70 years. In Sweden,

chest pain of ischemic origin is thought to affect 5% of all males aged 50-57years. In industrialized countries, annual incidence of unstable angina is

approximately 6 cases per 10,000 people.

Mortality/Morbidity: When the only treatment for angina was nitroglycerin andlimitation of activity, patients with newly diagnosed angina had a 40% incidence of MIand a 17% mortality rate within 3 months. A recent study shows that the 30-day mortality

from ACS has decreased as treatment has improved, a statistically significant 47%

relative decrease in 30-day mortality among newly diagnosed ACS from 1987-2000. Thisdecrease in mortality is attributed to aspirin, glycoprotein (GP) IIb/IIIa blockers, and

coronary revascularization via medical intervention or procedures.
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Clinical characteristics associated with a poor prognosis include advanced age, male sex,

prior MI, diabetes, hypertension, and multiple-vessel or left-mainstem disease.

Sex: Incidence is higher in males among all patients younger than 70 years. This is due tothe cardioprotective effect of estrogen in females. At 15 years postmenopause, the

incidence of angina occurs with equal frequency in both sexes. Evidence exists thatwomen more often have coronary events without typical symptoms, which might explain

the frequent failure to initially diagnose ACS in women.

Age: ACS becomes progressively more common with increasing age. In persons aged

40-70 years, ACS is diagnosed more often in men than in women. In persons older than

70 years, men and women are affected equally.

CLINICAL Section 3 of 10


History:

Typically, angina is a symptom of myocardial ischemia that appears in

circumstances of increased oxygen demand. It usually is described as a sensationof chest pressure or heaviness that is reproduced by activities or conditions that

increase myocardial oxygen demand.

Not all patients experience chest pain. Some present with only neck, jaw, ear,

arm, or epigastric discomfort. Other symptoms, such as shortness of breath or severe weakness, may represent

anginal equivalents.

A patient may present to the ED because of a change in pattern or severity ofsymptoms. A new case of angina is more difficult to diagnose because symptoms

are often vague and similar to those caused by other conditions (eg, indigestion,

anxiety).

Patients may have no pain and may only complain of episodic shortness of breath,weakness, lightheadedness, diaphoresis, or nausea and vomiting.

Patients may complain of the following:

o Palpitations

o Pain, which is usually described as pressure, squeezing, or a burning

sensation across the precordium and may radiate to neck, shoulder, jaw,

back, upper abdomen, or either arm
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o Exertional dyspnea that resolves with pain or rest

o Diaphoresis from sympathetic discharge

o Nausea from vagal stimulation

o Decreased exercise tolerance

o Patients with diabetes and elderly patients are more likely to have atypical

presentations and offer only vague complaints, such as weakness, dyspnea,

lightheadedness, and nausea.

Stable angina

o Involves episodic pain lasting 5-15 minutes

o Provoked by exertion

o Relieved by rest or nitroglycerin

Unstable angina: Patients have increased risk for adverse cardiac events, such as

MI or death. Three clinically distinct forms exist, as follows:

o New-onset exertional angina

o Angina of increasing frequency or duration or refractory to nitroglycerin

o Angina at rest

Variant angina (Prinzmetal angina)

o Occurs primarily at rest

o Triggered by smoking

o Thought to be due to coronary vasospasm

Physical:

Physical examination results are frequently normal. If chest pain is ongoing, thepatient usually will lie quietly in bed and may appear anxious, diaphoretic, andpale.

Hypertension may precipitate angina or reflect elevated catecholamines due to

either anxiety or exogenous sympathomimetic stimulation.


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Hypotension indicates ventricular dysfunction due to myocardial ischemia,

infarction, or acute valvular dysfunction.

Congestive heart failure (CHF)

Jugular venous distention

o Third heart sound (S3)

o A new murmur may reflect papillary muscle dysfunction

o Rales on pulmonary examination, suggesting left ventricular (LV)

dysfunction or mitral regurgitation

o Presence of a fourth heart sound (S4), a common finding in patients with

poor ventricular compliance due to preexisting ischemic heart disease or

hypertension

Causes:

Atherosclerotic plaque is the predominant cause. Coronary artery vasospasm isless common.

Alternative causes of angina include the following:

o Ventricular hypertrophy due to hypertension, valvular disease, or

cardiomyopathy

o Embolic occlusion of the coronary arteries

o Hypoxia, as in carbon monoxide poisoning or acute pulmonary disorders

o Cocaine and amphetamines, which increase myocardial oxygen demand

and may cause coronary vasospasm

o Underlying coronary artery disease, which may be unmasked by severe

anemia

o Inflammation of epicardial arteries

o Coronary artery dissection

Risk factors for ACS should be documented and include the following:

o Male gender


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o Diabetes mellitus (DM)

o Smoking history

o Hypertension

o Increased age

o Hypercholesterolemia

o Hyperlipidemia

o Prior cerebrovascular accident (CVA) - These patients constitute 7.5% of

patients with ACS and have high-risk features.

o Inherited metabolic disorders

o Methamphetamine use

o Occupational stress

o Connective tissue disease

DIFFERENTIALS Section 4 of 10


AnxietyAortic Stenosis

AsthmaCardiomyopathy, Dilated

Esophagitis

GastroenteritisHypertensive Emergencies

Myocardial Infarction
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Myocarditis

Pericarditis and Cardiac Tamponade

Pneumothorax, Iatrogenic, Spontaneous and PneumomediastinumPulmonary Embolism

WORKUP Section 5 of 10


Lab Studies:

Troponin I is considered the preferred biomarker for diagnosing myocardial

necrosis. Troponins have the greatest sensitivity and specificity in detecting MI,

and elevated serum levels are considered diagnostic of MI. They also haveprognostic value.

o For early detection of myocardial necrosis, sensitivity of troponin is

superior to that of the creatine kinaseMB (CK-MB). Troponin I isdetectable in serum 3-6 hours after an MI, and its level remains elevated

for 14 days.

o Troponin is a contractile protein that normally is not found in serum. It is

released only when myocardial necrosis occurs.

o Troponin should be used as the optimum biomarkers for the evaluation of

patients with ACS who have coexistent skeletal muscle injury.

Troponin T has similar release kinetics to troponin I and remains elevated for 14

days. False-positive results may occur in patients with renal failure. Minorelevations in troponin T also identify patients at risk for subsequent cardiac

events.

Elevated troponin levels may also point to minor myocardial injury due to other

causes. Zellweger et al described 4 patients with elevated troponin levels aftersupraventricular tachycardia without evidence of coronary artery disease and very

low risk scores for ACS. Similarly, Koller found that endurance athletes may

show elevated serum troponin levels in the absence of ACS.

CK-MB levels begin to rise within 4 hours after MI, peak at 18-24 hours, andsubside over 3-4 days. A level within the reference range does not exclude

myocardial necrosis.

o The upper limit of normal for CK-MB is 3-6% of total CK. A normal level

in the ED does not exclude the possibility of MI. A single assay in the EDhas a 34% sensitivity for MI. Serial sampling over periods of 6-9 hours
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increases sensitivity to approximately 90%. Serial CK-MB over 24 hours

detects myocardial necrosis with a sensitivity near 100% and a specificity

of 98%.

o Occasionally, a very small infarct will be missed by CK-MB; therefore,

troponin levels should be measured for patients suspected to have MI whohave negative results from serial CK-MB tests.

o One study looked at using the 2-hour delta (increase or decrease) of

cardiac markers as 1 of 6 criteria in making the diagnosis of ACS and MI.

According to one of the Erlanger criteria, an increase in the CK-MB level

of 1.5 ng/mL or greater or an increase of the cardiac troponin I level of 0.2ng/mL or greater over 2 hours in itself would allow one to make the

provisional diagnosis of ACS with a high degree of sensitivity and

specificity, even if the total levels were within the normal range. Patients

with recent MI were also identified by a decreasing curve of CK-MB.

Using this 2-hour delta of cardiac markers greatly reduces the number ofcases of MI and ACS that are overlooked in patients who are then

inappropriately discharged home.

Myoglobin, a low-molecular-weight heme protein found in cardiac and skeletal

muscle, is released more rapidly from infarcted myocardium than troponin and

CK-MB and may be detected as early as 2 hours after MI. Myoglobin levels,

although highly sensitive, are not cardiac specific. They may be useful for earlydetection of MI when performed with other studies.

Cardiac markers should be used liberally to evaluate patients with prolonged

episodes of ischemic pain, with new changes on ECG, or with nondiagnostic ornormal ECGs in whom the diagnosis of ACS or MI is being considered.

Complete blood count is indicated to determine if anemia is a precipitant.

Transfusion with packed red blood cells may be indicated.

Chemistry profile: Obtain a basic metabolic profile, including a check of blood

sugar level, renal function, and electrolytes levels, for patients with new-onsetangina. Potassium and magnesium levels should be monitored and corrected.

Creatinine levels must be considered before using an angiotensin-converting

enzyme (ACE) inhibitor.

Other biochemical markers

o C-reactive protein (CRP) is a marker of acute inflammation. Patients

without biochemical evidence of myocardial necrosis but elevated CRP

level are at increased risk of an adverse event.


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o Interleukin 6 is the major determinant of acute-phase reactant proteins in

the liver, and serum amyloid A is another acute-phase reactant. Elevations

of either of these can be predictive in determining increased risk ofadverse outcomes in patients with unstable angina.

In one study, patients presenting to the ED with suspected myocardial ischemiashowing higher levels of inflammatory cytokines were associated with an

increased risk of a serious cardiac event during the subsequent 3 months.However, the cytokines have limited ability to predict a serious adverse cardiac

event.

Erythrocyte sedimentation rate rises above reference range values within 3 daysand may remain elevated for weeks.

Serum lactase dehydrogenase level rises above the reference range within 24

hours of MI, reaches a peak within 3-6 days, and returns to the baseline within 8-

12 days.

Imaging Studies:

Chest radiograph may demonstrate complications of ischemia, such as pulmonary

edema, or provide clues to alternative causes of symptoms, such as thoracic

aneurysm or pneumonia.

Echocardiogram often demonstrates wall motion abnormalities due to ischemia. Itis of limited value in patients whose symptoms have resolved or in those with

preexisting wall motion abnormalities. However, echocardiogram may be useful

in identifying precipitants for ischemia, such as ventricular hypertrophy andvalvular disease.

Radionuclide myocardial perfusion imaging has been shown to have favorable

diagnostic and prognostic value in this setting, with an excellent early sensitivity

to detect acute myocardial infarction (MI) not achieved by other testingmodalities.

o A normal resting perfusion imaging study has been shown to have a

negative predictive value of more than 99% in excluding MI.Observational and randomized trials of both rest and stress imaging in the

ED evaluation of patients with chest pain have demonstrated reductions in

unnecessary hospitalizations and cost savings compared with routine care.o Perfusion imaging has also been used in risk stratification after MI and for

measurement of infarct size to evaluate reperfusion therapies. Novel "hot

spot" imaging radiopharmaceuticals that visualize infarction or ischemia

are currently undergoing evaluation and hold promise for future imagingof ACS. (See Myocardial Ischemia - Nuclear Medicine and Risk

Stratification.)
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Multislice spiral computed tomography (MSCT) is a new, noninvasive imaging

technique for detecting coronary artery disease. It allows direct visualization of

not only the lumen of the coronary arteries but also plaque within the artery. Afew studies are present in the literature with more underway that may eventually

allow MSCT angiography to determine in real-time presence or absence of

significant coronary artery stenosis or occlusion. This modality does not yet havea weight of evidence to allow its use in the ED as a standard of care to determine

or rule-out coronary artery disease.

Technetium-99m (99mTc) tetrofosmin single-photon emission computed

tomography (SPECT) is a useful method to exclude high-risk patients amongpatients with chest pain in the emergency department.

Resting cardiac magnetic resonance (MR) imaging has exhibited diagnostic

operating characteristics suitable for triage of patients with chest pain in the ED.

Performed urgently to evaluate chest pain, MR accurately detected a high fraction

of patients with ACS, including patients with enzyme-negative unstable angina.MR can identify wall thinning, scar, delayed enhancement (infarction), and wall

motion abnormalities (ischemia). Coronary artery assessment may be coupledwith MR angiography in the future.

Other Tests:

ECG is the most important ED diagnostic test for angina. It may show changes

during symptoms and in response to treatment, which would confirm a cardiac

basis for symptoms. It also may demonstrate preexisting structural or ischemicheart disease (left ventricular hypertrophy, Q waves). A normal ECG or one that

remains unchanged from the baseline does not exclude the possibility that chest pain is ischemic in origin. Changes that may be seen during anginal episodesinclude the following:

o Transient ST-segment elevations (fixed changes suggest acute MI): In

patients with elevated ST segments, consider LV aneurysm, pericarditis,

Prinzmetal angina, early repolarization, and Wolff-Parkinson-Whitesyndrome as possible diagnoses.

o Dynamic T-wave changes (inversions, normalizations, or hyperacute

changes): In patients with deep T-wave inversions, consider also CNS

events or drug therapy with tricyclic antidepressants or phenothiazines.

o ST depressions that may be junctional, downsloping, or horizontal

o Diagnostic sensitivity may be increased by performing right-sided leads

(V4R), posterior leads (V8, V9), and serial recordings.

TREATMENT Section 6 of 10
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Prehospital Care: Generally, patients transported with chest pain should initially bemanaged under the assumption that the pain is ischemic in origin. Prehospital

interventions should be guided by the nature of the presenting complaint, individual riskfactors, and associated symptoms (eg, breathing difficulty, hemodynamic instability,

appearance of ectopy). Airway, breathing, and circulation should be rapidly assessed withinstitution of CPR, ACLS-guided interventions, or other measures as indicated for the

unstable patient.

Obtain IV access.

Administer supplemental oxygen.

Aspirin may be given in the field, 162-325 mg PO.

Telemetry and prehospital ECG, if available, may be helpful in selectedcircumstances. Certain EMS systems have investigated protocols for prehospital

administration of thrombolytic therapy. This has not become a trend due tounproven benefit and due to the increase in availability of percutaneous coronary

intervention (PCI) in many medical centers as an alternative to thrombolysis for

STEMI.

Perform pulse oximetry.

Administer sublingual or aerosolized nitroglycerin if chest pain is ongoing and is

felt to be cardiac in origin.

Emergency Department Care: The ACS spectrum concept is a useful framework for

developing therapeutic strategies. Antithrombin therapy and antiplatelet therapy shouldbe administered to all patients with an ACS regardless of the presence or the absence of

ST-segment elevation. Patients presenting with persistent ST-segment elevation are

candidates for reperfusion therapy (either pharmacological or catheter based) to restoreflow promptly in the occluded epicardial infarct-related artery. Patients presenting

without ST-segment elevation are not candidates for immediate pharmacological

reperfusion but should receive anti-ischemic therapy and PCI when appropriate. "Time is

myocardium" is a dictum to be remembered as survival has been shown to correlate withtime to reperfusion in patients with acute MI. Many centers set goals for, and routinely

record, door-to-ECG, door-to-needle (thrombolytic therapy), or door-to-vascular access(for patients receiving PCI) times as measures of quality of care provided.

Goals of ED care are rapid identification of patients with STEMI, exclusion ofalternative causes of nonischemic chest pain, and stratification of patients with

acute coronary ischemia into low- and high-risk groups.
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Obtain IV access, administer supplemental oxygen, and provide telemetry

monitoring if these procedures have not already been accomplished in the

prehospital phase. In addition, obtain a 12-lead ECG as soon as possible afterarrival.

Complete a history and physical examination, with focus on risk factors forcoronary ischemia; onset, duration, and pattern of symptoms; and early

identification of complications of myocardial ischemia (eg, new murmurs, CHF).

Perform frequent reassessment of vital signs and symptoms in response to

administered therapies.

Serial ECGs and continuous ST segment monitoring may be useful.

Many EDs have an observation unit that may be an appropriate disposition for

patients who meet admission criteria.

Medical therapy as discussed inMedication.

Consultations: Cardiology or interventional cardiology consultation may be indicated

for patients with any of the following:

STEMI - Depending on the center, the patient may be a candidate for PCI and

immediate interventional cardiology consultation is indicated.

o Ongoing symptoms highly suggestive of acute coronary ischemia and

nondiagnostic ECG (eg, left bundle-branch block [LBBB])

o Ongoing symptoms refractory to aggressive medical therapy

o Hemodynamic instability

o Evidence of acute valvular dysfunction

o Shock

o Known severe aortic stenosis and ongoing symptoms

o Uncertainty of the diagnosis

MEDICATION Section 7 of 10


The goals of treatment are to preserve patency of the coronary artery, augment blood

flow through stenotic lesions, and reduce myocardial oxygen demand. All patients should
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receive antiplatelet agents, and patients with evidence of ongoing ischemia should receive

aggressive medical intervention until signs of ischemia, as determined by symptoms and

ECG, resolve.

Drug Category: Antiplatelet agents -- Inhibit the cyclooxygenase system, decreasing the

level of thromboxane A2, which is a potent platelet activator. Antiplatelet therapy hasbeen shown to reduce mortality by reducing the risk of fatal strokes and fatal myocardial

infarctions.

Drug Name

Aspirin (Anacin, Ascriptin, Bayer Aspirin) -- Early

administration of aspirin in patients with AMI may reduce

cardiac mortality in first mo.

Adult Dose160-324 mg PO or chewed; suppository if patient is unableto take PO medications

Pediatric Dose Not established

ContraindicationsDocumented hypersensitivity; liver damage;hypoprothrombinemia; vitamin K deficiency; bleeding

disorders; asthma; children (2 g/d maypotentiate glucose-lowering effect of sulfonylurea drugs

Pregnancy D - Unsafe in pregnancy

Precautions

May cause transient decrease in renal function and

aggravate chronic kidney disease; avoid use in severe

anemia, history of blood coagulation defects, or patientstaking anticoagulants

Drug Category: Nitrates -- These agents oppose coronary artery spasm and reducemyocardial oxygen demand by reducing both preload and afterload.

Drug Name

Nitroglycerin (Nitro-Bid) -- Causes relaxation of the

vascular smooth muscle via stimulation of intracellularcyclic guanosine monophosphate production, causing adecrease in blood pressure.

Adult Dose 400 mcg SL or spray q5min, repeated up to 3 times

If symptoms persist, administer 5-10 mcg/min IV infusion

Dose should be titrated to reduce MAP by 10%, relievesymptoms, limit adverse effects of hypotension (>30%


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reduction in MAP or


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Drug Category: Anticoagulants -- These agents are used to prevent recurrence of clot

after a spontaneous fibrinolysis.

Drug Name

Heparin -- Augments activity of antithrombin III and

prevents conversion of fibrinogen to fibrin. Does not

actively lyse but is able to inhibit further thrombogenesis.Prevents recurrence of a clot after spontaneous fibrinolysis.

Adult Dose 80 U/kg IV bolus, followed by an infusion of 18 U/kg/h


Contraindications

Documented hypersensitivity; diagnosed subacute bacterialendocarditis; active bleeding; history of heparin-induced

thrombocytopenia

Interactions

Digoxin, nicotine, tetracycline, and antihistamines may

decrease effects; NSAIDs, aspirin, dextran, dipyridamole,and hydroxychloroquine may increase heparin toxicity

PregnancyC - Safety for use during pregnancy has not been

established.

Precautions

Observe for prolonged or excessive bleeding at

venipuncture sites; some preparations contain benzylalcohol as a preservative; benzyl alcohol, used in large

amounts, has been associated with fetal toxicity (gasping

syndrome); use of preservative-free heparin isrecommended in neonates; use with caution in patients

diagnosed with shock or severe hypotension

Drug Category: Beta-adrenergic blockers -- These agents have antiarrhythmic andantihypertensive properties as well as the ability to reduce ischemia. They minimize the

imbalance between myocardial supply and demand by reducing afterload and wall stress.In patients with acute MI, they have been shown to decrease infarct size as well as short-

and long-term mortality, which is a function of their anti-ischemic and antiarrhythmic

properties.

Drug Name

Metoprolol (Lopressor) -- Selective beta1-adrenergicreceptor blocker that decreases the automaticity of

contractions.

During IV administration, carefully monitor blood pressure,

heart rate, and ECG. Goal of treatment is to reduce heartrate to 60-90 beats/min.

Adult Dose5 mg slow IV infusion q5min; to a maximum dose of 15 mg

or desired heart rate


Contraindications Documented hypersensitivity; uncompensated congestiveheart failure; bradycardia; asthma; cardiogenic shock; AV


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conduction abnormalities

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium

salts, cholestyramine, and rifampin may decrease

bioavailability and plasma levels of metoprolol, possiblyresulting in decreased pharmacologic effects; toxicity of

metoprolol may increase with coadministration ofsparfloxacin, phenothiazines, astemizole (recalled from US

market), calcium channel blockers, quinidine, flecainide,

and contraceptives; metoprolol may increase toxicity of

digoxin, flecainide, clonidine, epinephrine, nifedipine,prazosin, verapamil, and lidocaine


established.

Precautions

Beta-adrenergic blockade may reduce signs and symptoms

of acute hypoglycemia and may decrease clinical signs of

hyperthyroidism; abrupt withdrawal may exacerbatesymptoms of hyperthyroidism, including thyroid storm;

monitor patients closely and withdraw the drug slowly;during IV administration, carefully monitor blood pressure,

heart rate, and ECG

Drug Name

Esmolol (Brevibloc) -- Excellent drug for use in patients at

risk for complications from beta-blockers, particularly

reactive airway disease, mild-to-moderate LV dysfunction,and peripheral vascular disease. Short half-life of 8 min

allows for titration to desired effect with ability to stop

quickly prn.

Adult Dose

Initial maintenance dose: 0.1 mg/kg/min IV; titrate inincrements of 0.05 mg/kg/min q10-15min to a total dose of

0.2 mg/kg/min

Optional loading dose: 0.5 mg/kg slow IV infusion


Contraindications

Documented hypersensitivity; uncompensated congestiveheart failure; bradycardia; cardiogenic shock; AV

conduction abnormalities

Interactions Aluminum salts, barbiturates, NSAIDs, penicillins, calcium

salts, cholestyramine, and rifampin may decrease

bioavailability and plasma levels, possibly resulting in adecreased pharmacologic effect; conversely, cardiotoxicity

of sotalol may increase when coadministered withsparfloxacin, astemizole (recalled from US market),

calcium channel blockers, quinidine, flecainide, or

contraceptivesToxicity of sotalol increases when administered


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concurrently with digoxin, flecainide, acetaminophen,

clonidine, epinephrine, nifedipine, prazosin, haloperidol,

phenothiazines, or catecholamine-depleting agents

PregnancyC - Safety for use during pregnancy has not beenestablished.

Precautions

Do not use in cocaine-related ischemia; beta-adrenergic

blockade may decrease the signs and symptoms of acute

hypoglycemia and the clinical signs of hyperthyroidism;abrupt withdrawal may exacerbate symptoms of

hyperthyroidism, including thyroid storm; slowly withdraw

drug; closely monitor patients

Drug Category: Glycoprotein IIB/IIA inhibitors -- Glycoprotein (GP) IIb/IIIa antagonists

prevent the binding of fibrinogen, thereby blocking platelet aggregation. Studies to datesuggest that as a class, the addition of intravenous GP IIb/IIIa inhibitors to aspirin and

heparin improves both early and late outcomes, including mortality, Q-wave MI, need forrevascularization procedures, and length of hospital stay.

Currently, IIb/IIIb antagonists in combination with aspirin are considered standardantiplatelet therapy for patients at high risk for unstable angina. Adenosine diphosphate

(ADP) antagonists are not considered standard therapy but may be used in patients unable

to tolerate aspirin.

Drug Name

Abciximab (ReoPro) -- Chimeric human-murinemonoclonal antibody. Binds to receptor with high affinity

and reduces platelet aggregation by 80%. Inhibition of

platelet aggregation persists for up to 48 h after end ofinfusion.

Abciximab has been approved for use in

elective/urgent/emergent percutaneous coronaryintervention.

Adult Dose0.25 mg/kg bolus IV followed by an infusion of 0.125

mcg/kg/min; maximum 10 mcg/min for 12 h


Contraindications

Documented hypersensitivity; bleeding diathesis;

thrombocytopenia (>100,000 cells/mcL); recent trauma;

intracranial tumor and/or hemorrhage; severe uncontrolledhypertension; history of vasculitis; cerebrovascular accident

within 2 years; active internal bleeding; intracranialhemorrhage; hemorrhagic stroke; severe HTN (systolic BP

>200 mm Hg, or diastolic BP >110 mm Hg); major surgical

procedure within the past mo

InteractionsToxicity increases with coadministration of anticoagulants,antiplatelets, and thrombolytics


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established.

Precautions

Bleeding complications may occur in patients 65

years, with history of GI disease, or recently receivedthrombolytic therapy; severe thrombocytopenia may occur

within first 24 h of usePatients receiving other drugs that affect hemostasis (eg,thrombolytics, NSAIDs, dipyridamole, ticlopidine,

clopidogrel)

Drug Name

Eptifibatide (Integrilin) -- Antagonist of the platelet GP

IIb/IIIa receptor, which reversibly prevents von Willebrand

factor, fibrinogen, and other adhesion ligands from bindingto the GP IIb/IIIa receptor. End effect is the inhibition of

platelet aggregation. Effects persist over duration of

maintenance infusion and are reversed when infusion ends.

Adult Dose

Unstable angina: 180 mcg/kg IV bolus, followed by acontinuous infusion of 2 mcg/kg/min until discharge or

surgery

Patients undergoing PCI: 135 mcg/kg IV bolus; administer before PCI, followed by a continuous infusion of 0.5

mcg/kg/min


Contraindications

Documented hypersensitivity; severe hypertension (SBP

>200 mm Hg); active internal bleeding; history ofintracranial hemorrhage; intracranial neoplasm,

arteriovenous malformation, or aneurysm; acute pericarditis;

bleeding diathesis; trauma or stroke within previous 30 d;platelet count 2 mg/dL (for 180mcg/kg bolus and 2 mcg/kg/min infusion) or >4 mg/dL (for

135 mcg/kg bolus and 0.5 mcg/kg/min infusion)

History of bleeding diathesis within 30 d; intracranialhemorrhage; history of hemorrhagic stroke; severe HTN

(systolic BP >200 mm Hg, or diastolic BP >110 mm Hg);

major surgical procedure within the past mo

Interactions

When used with heparin and aspirin, an increase inbleeding, compared with using heparin and aspirin alone,

can occur

If using concurrently with other drugs that affect hemostasis

(eg, warfarin), closely monitor patients


established.


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Precautions

Most common complications encountered during therapy

with eptifibatide are bleeding events; caution in patients

with a platelet count 200 mm Hg, or diastolic BP >110 mm Hg);

major surgical procedure within the past mo

Interactions When used with heparin and aspirin, an increase in


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bleeding, compared with using heparin and aspirin alone,

can occur

If using concurrently with other drugs that affect hemostasis(eg, warfarin), closely monitor patients

Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions

Most common complications in therapy with tirofiban are

bleeding events; caution in patients with platelet counts


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combination of eptifibatide with enoxaparin appears to have a more potent antithrombotic

effect than that of eptifibatide and unfractionated heparin (UFH).

Drug Name

Enoxaparin (Lovenox) -- LMWH is produced by partial

chemical or enzymatic depolymerization of UFH. Binds to

antithrombin III, enhancing its therapeutic effect. Theheparin-antithrombin III complex binds to and inactivates

activated factor X (Xa) and factor II (thrombin). LMWHdiffers from unfractionated heparin by having a higher ratio

of antifactor Xa to antifactor IIa compared to UFH.

Adult Dose

1 mg/kg administered SC q12h in conjunction with oral

aspirin (100-325 mg/d); maximum antifactor Xa andantithrombin activities occur 3-5 h postadministration


ContraindicationsDocumented hypersensitivity; major bleeding;

thrombocytopenia

Interactions

Platelet inhibitors or oral anticoagulants (eg, dipyridamole,salicylates, aspirin, NSAIDs, sulfinpyrazone, ticlopidine)

may increase risk of bleeding


Precautions

If thromboembolic event occurs despite LMWH

prophylaxis, discontinue drug and initiate alternate therapy;elevation of hepatic transaminases may occur but is

reversible; heparin-associated thrombocytopenia may occur

with fractionated LMWHs; 1 mg of protamine sulfate will

reverse effect of approximately 1 mg of enoxaparin ifsignificant bleeding complications develop

Drug Category:Direct thrombin inhibitors -- Hirudin is the prototype of direct thrombin

inhibitors. Hirudin binds directly to the anion binding site and the catalytic sites of

thrombin to produce potent and predictable anticoagulation.

Drug Name

Hirudin (Lepirudin, Refludan) -- When compared tounfractionated heparin in unstable angina trials, hirudin

demonstrated a modest short-term reduction in the

composite end point of death or nonfatal MI. Risk of

bleeding is increased modestly. Currently, hirudin isindicated only in patients unable to receive heparin because

of heparin-induced thrombocytopenia.

Adult Dose

0.4 mg/kg IV bolus over 15-20 s, followed by a continuousinfusion of 0.15 mg/kg/h; goal is to increase aPTT 1.5-2.5

times the control; adjust dosing in renal impairment



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Contraindications Documented hypersensitivity

Interactions

Intracranial bleeding may be life threatening following

concomitant thrombolytic therapy with rt-PA or

streptokinase


Precautions

Associated with an increased need for transfusion

(compared to unfractionated heparin) and increased risk of

intracranial hemorrhage; no specific antidote exists; if life-threatening bleeding occurs, stop administration, determine

coagulation profiles, send T/S, and prepare for blood

transfusion

Drug Name

Bivalirudin (Angiomax) -- Used for anticoagulation in

unstable angina undergoing PTCA. Synthetic analogue ofrecombinant hirudin. Inhibits thrombin. Potential

advantages over conventional heparin therapy include more

predictable and precise levels of anticoagulation, activityagainst clot-bound thrombin, absence of natural inhibitors

(eg, platelet factor 4, heparinase), and continued efficacy

following clearance from plasma (because of binding to

thrombin).

Adult Dose

1 mg/kg IV bolus initially; followed by 2.5 mg/kg/h IV for 4

h; may administer additional IV infusion at 0.2 mg/kg/h (not

to exceed 20 h); administer with aspirin 325 mg/d


Contraindications

Documented hypersensitivity; cerebral aneurysm;

intracranial hemorrhage, general uncontrollablehemorrhage, or active major bleeding

Interactions

Coadministration with antiplatelets (other than aspirin) or

other anticoagulants has not been evaluated fully, usecaution


Precautions

Caution in renal impairment (adjust dose), recent surgery or

trauma, GI ulceration; risk of bleeding; may cause back

pain, nausea, headache, hypotension

Drug Category: Adenosine diphosphate receptor antagonists -- Two thienopyridines,ticlopidine and clopidogrel, are ADP antagonists that are approved for antiplatelet

activity. Both have irreversible antiplatelet activity but take several days to become

manifest. A potential additive benefit exists when ADP antagonists are used in

conjunction with aspirin.These drugs may be considered alternatives to aspirin in patients intolerant or allergic to

aspirin.


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Drug Name

Clopidogrel (Plavix) -- Generally preferred over ticlopidine

because it more rapidly inhibits platelets and appears to

have a more favorable safety profile.

Adult Dose 300 mg PO loading dose, followed by 75 mg PO qd


ContraindicationsDocumented hypersensitivity; active bleeding; peptic ulcer

or CNS hemorrhage

Interactions

Safety of concomitant use of heparin not established;

coadministration with NSAIDS is associated with increasedgastrointestinal bleeding


Precautions

TTP has been reported rarely after use of Plavix; caution in

patients at risk of bleeding from trauma, surgery, or other

pathological conditions; caution in prolonged bleeding

time/liver disease

Drug Name

Ticlopidine (Ticlid) -- Beneficial effects were noted in

patients with UA after 2 wk of use in one randomized trial.

When compared to controls, ticlopidine use decreasedvascular deaths and nonfatal MIs.

Adult Dose 250 mg PO bid


Contraindications

Documented hypersensitivity; presence of neutropenia or

thrombocytopenia or a past history of either TTP or aplastic

anemia; hemostatic disorder or active bleeding; severe liver

impairment

Interactions

Effects may decrease with coadministration of

corticosteroids and antacids; toxicity increases when taken

concurrently with theophylline, cimetidine, aspirin, andNSAIDS


Precautions

Discontinue if absolute neutrophil count decreases to


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Patients with unstable angina and/or ECG changes should be admitted to a

telemetry bed. A certain subset of patients with stable angina may be treated as

outpatients with antianginal agents, but close follow-up is necessary.

Patients with symptoms refractory to aggressive medical treatment, shock,

suspected or known aortic stenosis, or new or worsening mitral regurgitation areat high risk. Management for these patients should include the following:

o Admission to an intensive care unit setting

o Cardiology consultation

Consideration for intra-aortic balloon pump (IABP) and early angiography to

delineate anatomy

Continue antiplatelet and antianginal medications initiated in the ED. Subsequent

dosing is determined by symptomatic response and tolerance of side effects.

The routine use of lidocaine as prophylaxis for ventricular arrhythmias in patients

with ACS is not indicated. In MI, it has been shown to increase mortality rates.

Lidocaine may be used for patients with complex ventricular ectopy or for

patients with hemodynamically significant, nonsustained, or sustained ventriculartachycardia.

Further Outpatient Care:

Patients with chronic stable angina may be considered for discharge after

occurrence of the following:

o Symptom duration is brief and identical to symptoms experienced in the

past.

o ECG is normal or unchanged.

o Patient has access to timely follow-up with a primary care physician.

When in doubt, admit. The usual reason for a patient with chronic stable angina topresent to the ED is a change in pattern or severity of symptoms, which makes

their angina unstable.

A recent study by Bartholomew et al may be helpful in making the decision to

admit or discharge. This prospective thrombolysis in myocardial infarction riskscore (TIMI-RS) used 7 variables in patients with suspected ACS: (1) age older

than 65, (2) 3 or more cardiac risk factors, (3) ST deviation, (4) aspirin use within

7 days, (5) 2 or more anginal events over 24 hours, (6) history of coronary


26/29

stenosis, and (7) elevated troponin levels. Patients were contacted at 30 days and

data was collected concerning major adverse cardiac events.

o In patients presenting with chest pain, a higher TIMI-RS was associated

with an increase in major adverse cardiac events within 30 days. The

authors concluded that the 30-day event rate was 0% for a score of 1, 20%for a score of 2, 24% for a score of 3, 42% for a score of 4, 52% for a

score of 5, and 70% for a score of 6 or 7 (p < 0.0001).

o The TIMI-RS successfully differentiates early risk for major adverse

cardiac events in a general population presenting with symptoms

suggestive of ACS. A simple bedside calculation of the TIMI-RS providesrapid risk stratification, allowing facilitation of therapeutic decision-

making in patients with symptoms suggestive of ACS and may be helpful

with the patient's disposition.

In/Out Patient Meds:

Aspirin

o Use clopidogrel as a substitute for patients unable to take aspirin because

of a history of hypersensitivity or bleeding.

o Use a 300-mg loading dose, then 75 mg qd.

Nitrates

o Use topical or oral nitrates for those who are discharged or for those who

are stable inpatients.

o Intravenous infusion is preferable for those admitted with unstable

symptoms.

Beta-blockers

o Metoprolol and propranolol are excellent choices for inpatient and

outpatient management.

o Use esmolol for inpatient treatment, particularly those at risk for adverse

effects from beta-blockade.

Heparin: Use heparin for inpatient management of unstable angina. Some

preliminary data suggest that LMWH is a safe and effective alternative.

Significant clustering of recurrent ischemic events occurs within 24 hours after

cessation of both short-term UFH and enoxaparin treatment, and patients should


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be carefully monitored during that period. This early rebound may be prevented

by continuation of a fixed dose of enoxaparin.

Transfer:

Consider transfer only for particularly patients at particularly high risk and forthose who are being evaluated in a center without access to timely cardiac

catheterization, PTCA, or bypass.

High-risk criteria include the following:

o Symptoms refractory to medical management

o Hemodynamic instability, cardiogenic shock

o New or worsening mitral regurgitant murmur

o Known or suspected severe aortic stenosis

The risks of transferring these unstable patients must be carefully weighed against

the benefits of transfer.

Deterrence/Prevention:

Cessation of smoking

Assessment of lipid profile and dietary changes, where appropriate (Among

patients who have recently had an ACS, an intensive lipid-lowering statin regimenprovides greater protection against death or major cardiovascular events than astandard regimen [Cannon, 2004].)

Blood pressure control

Compliance with medications, particularly aspirin

Comprehensive risk assessment by primary care physician, including exercise

tolerance test (ETT) for individuals at high risk and identification of structuralheart disease (eg, left ventricular hypertrophy [LVH], aortic stenosis)

Complications:

Acute myocardial infarction

Cardiogenic shock

Ischemic mitral regurgitation


28/29

Arrhythmias

o Supraventricular arrhythmias (rare complication of ischemia, may actually

precipitate ischemic events)

o Ventricular arrhythmias; simple and complex premature ventricularcontractions (PVCs), and nonsustained ventricular tachycardia (NSVT)

Atrioventricular nodal blockade

o Usually transient in setting of reversible ischemia

o Treatment guided by location of block and hemodynamic stability.

Ventricular rupture occurs in the interventricular septum or the LV free wall. Thisrepresents a catastrophic event with mortality rates greater than 90%. Prompt

recognition, stabilization, and surgical repair are crucial to any hope of survival.An echocardiogram usually will define the abnormality, and a right heartcatheterization may show an oxygenation increase with septal rupture.

Prognosis:

Patients with angina either go on to infarct or have their disease stabilized by

medical and/or interventional therapies. Patients with angina are a heterogeneous

group; therefore, prognosis varies with respect to stability of disease,demographics, comorbidity, and current intervention.

Patients with ACS with atrial fibrillation (AF) are associated with increased

morbidity and mortality (Mehta, 2003). Patients with ACS and DM, especially those with ST elevation, had increased in-

hospital mortality. Among patients with ACS and DM, those receiving insulin had

worse outcomes. Outcomes were similar for those on hypoglycemic medication oron diet alone (Hasdai, 2003).

In chronic stable angina, prognosis is generally excellent. Factors that have been

shown to impact prognosis include the following:

o Aspirin reduces progression to both nonfatal MI and cardiac death.

o Beta-blockers control anginal symptoms and reduce cardiac complicationsin patients with hypertension.

o PTCA and revascularization improve the prognosis in high-risk patients.

o Poor prognostic factors include male sex, diabetes, and hypertension.


29/29

In unstable angina, prognosis is determined by the ability to control symptoms

acutely, preventing progression to AMI. Factors associated with a poorer

prognosis include the following:

o Evidence of myocardial necrosis, as determined by elevated troponin T

o Delays in angiography in patients at high risk (Early angiography allows

for triage to medical therapy, PTCA, or revascularization.)

Patient Education:

For patients being discharged home, emphasize the following:

o Timely follow-up with primary care physician

o Compliance with discharge medications, specifically aspirin and other

medications used to control symptoms

o Need to return to ED for any change in frequency or severity of symptoms

MISCELLANEOUS Section 9 of 10


Medical/Legal Pitfalls:

Failure to consider the diagnosis - Groups at risk include the following:

o Women, particularly premenopausal

o Diabetics

o Elderly

o Patients with cocaine-related ischemia

Inadequate risk stratification in ED

Failure to administer aspirin as first-line therapy

Overcautious use of beta-blockers in ED
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