Alan Dwi Setiawan

01071200089

LO dan WO Week 4 Cardio (Jumat)

1. All about ACS

 Bedanya CAD dan ACS

CAD =

Coronary artery disease is a narrowing or blockage of your coronary arteries usually caused
by the buildup of fatty material called plaque. Coronary artery disease is also called coronary
heart disease, ischemic heart disease and heart disease.

Coronary artery disease is caused by atherosclerosis. Atherosclerosis is the buildup of plaque

inside your arteries. Plaque consists of cholesterol, fatty substances, waste products, calcium
and the clot-making substance fibrin. As plaque continues to collect on your artery walls,
your arteries narrow and stiffen. Plaque can clog or damage your arteries, which limits or
stops blood flow to your heart muscle. If your heart does not get enough blood, it can't get the
oxygen and nutrients it needs to work properly. This condition is called ischemia. Not getting
enough blood supply to your heart muscle can lead to chest discomfort or chest pain
(called angina). It also puts you at risk for a heart attack.

You have an increased risk of coronary artery disease if you:

 Have a high cholesterol level (especially a high LDL “bad” cholesterol level and a

low HDL “good” cholesterol level).
 Have high blood pressure.
 Family history of heart disease.
 Have diabetes.
 Are a smoker.
 Are a man over 45 years of age or a post-menopausal woman.
 Are overweight.
 Are physically inactive.
 Are Black, Mexican American, Native American, Native Hawaiian or an Asian
American. The increased risks are caused by higher rates of high blood pressure,
obesity and diabetes in these populations.

Sumber = https://my.clevelandclinic.org/health/diseases/16898-coronary-artery-
disease

ACS =

Acute coronary syndrome is a term used to describe a range of conditions associated with
sudden, reduced blood flow to the heart.
One such condition is a heart attack (myocardial infarction) — when cell death results in
damaged or destroyed heart tissue. Even when acute coronary syndrome causes no cell death,
the reduced blood flow changes how your heart works and is a sign of a high risk of heart
attack.

Acute coronary syndrome often causes severe chest pain or discomfort. It is a medical
emergency that requires prompt diagnosis and care. The goals of treatment include improving
blood flow, treating complications and preventing future problems.

Symptoms

The signs and symptoms of acute coronary syndrome usually begin abruptly. They include:

 Chest pain (angina) or discomfort, often described as aching, pressure, tightness or

burning

 Pain spreading from the chest to the shoulders, arms, upper abdomen, back, neck or
jaw

 Nausea or vomiting

 Indigestion

 Shortness of breath (dyspnea)

 Sudden, heavy sweating (diaphoresis)

 Lightheadedness, dizziness or fainting

 Unusual or unexplained fatigue

 Feeling restless or apprehensive

Causes

Acute coronary syndrome usually results from the buildup of fatty deposits (plaques) in and
on the walls of coronary arteries, the blood vessels delivering oxygen and nutrients to heart
muscles.

When a plaque deposit ruptures or splits, a blood clot forms. This clot blocks the flow of
blood to heart muscles.
When the supply of oxygen to cells is too low, cells of the heart muscles can die. The death
of cells — resulting in damage to muscle tissues — is a heart attack (myocardial infarction).

Even when there is no cell death, the decrease in oxygen still results in heart muscles that
don't work the way they should. This change may be temporary or permanent. When acute
coronary syndrome doesn't result in cell death, it is called unstable angina.

Risk factors

The risk factors for acute coronary syndrome are the same as those for other types of heart
disease. Acute coronary syndrome risk factors include:

 Aging

 High blood pressure

 High blood cholesterol

 Cigarette smoking

 Lack of physical activity

 Unhealthy diet

 Obesity or overweight

 Diabetes

 Family history of chest pain, heart disease or stroke

 History of high blood pressure, preeclampsia or diabetes during pregnancy

 COVID-19 infection

Sumber : https://www.mayoclinic.org/diseases-conditions/acute-coronary-
syndrome/symptoms-causes/syc-20352136

 Bedanya apa, mana lebih bahaya, characteristics chest pain, mana yg ACS
mana yg CAD

Coronary artery disease can lead to:

  Chest pain (angina). When your coronary arteries narrow, your heart may not
receive enough blood when demand is greatest — particularly during physical activity.
This can cause chest pain (angina) or shortness of breath.

 Heart attack. If a cholesterol plaque ruptures and a blood clot forms, complete
blockage of your heart artery may trigger a heart attack. The lack of blood flow to your
heart may damage your heart muscle. The amount of damage depends in part on how
quickly you receive treatment.

 Heart failure. If some areas of your heart are chronically deprived of oxygen and
nutrients because of reduced blood flow, or if your heart has been damaged by a heart
attack, your heart may become too weak to pump enough blood to meet your body's
needs. This condition is known as heart failure.

 Abnormal heart rhythm (arrhythmia). Inadequate blood supply to the heart or

damage to heart tissue can interfere with your heart's electrical impulses, causing
abnormal heart rhythms.

Acute coronary syndrome (ACS) refers to a spectrum of clinical presentations ranging from
those for ST-segment elevation myocardial infarction (STEMI) to presentations found in
non–ST-segment elevation myocardial infarction (NSTEMI) or in unstable angina. It is
almost always associated with rupture of an atherosclerotic plaque and partial or complete
Signs and symptoms

Atherosclerosis is the primary cause of ACS, with most cases occurring from the disruption
of a previously nonsevere lesion. Complaints reported by patients with ACS include the
following:
 Palpitations
 Pain, which is usually described as pressure, squeezing, or a burning sensation across
the precordium and may radiate to the neck, shoulder, jaw, back, upper abdomen, or
either arm
 Exertional dyspnea that resolves with pain or rest
 Diaphoresis from sympathetic discharge
 Nausea from vagal stimulation
 Decreased exercise tolerance

Physical findings can range from normal to any of the following:

 Hypotension: Indicates ventricular dysfunction due to myocardial ischemia,
myocardial infarction (MI), or acute valvular dysfunction
 Hypertension: May precipitate angina or reflect elevated catecholamine levels due to
anxiety or to exogenous sympathomimetic stimulation
 Diaphoresis
 Pulmonary edema and other signs of left heart failure
 Extracardiac vascular disease
 Jugular venous distention
 Cool, clammy skin and diaphoresis in patients with cardiogenic shock
 A third heart sound (S3) and, frequently, a fourth heart sound (S4)
 A systolic murmur related to dynamic obstruction of the left ventricular outflow tract
  Rales on pulmonary examination (suggestive of left ventricular dysfunction or mitral
regurgitation)

Potential complications include the following:

 Ischemia: Pulmonary edema
 Myocardial infarction: Rupture of the papillary muscle, left ventricular free wall, and
ventricular septum
Sumber : https://emedicine.medscape.com/article/1910735-overview

 ( UA , NSTEMI, STEMI) mana yg paling bahaya, terapi untuk masing-

masing jenis, yang mana yg kemasuk UA, mana yg NSTEMI, mana yang
STEMI.

The term “acute coronary syndrome” encompasses unstable angina and non–ST-segment
elevation myocardial infarction (UA/NSTEMI) and ST-segment elevation myocardial
infarction (STEMI). UA/NSTEMI is the combination of two closely related clinical entities
(i.e., a syndrome), whereas STEMI is a distinct clinical entity. UA/NSTEMI is characterized
by an imbalance between myocardial oxygen supply and demand. Most often, the syndrome
develops because of decreased myocardial perfusion resulting from coronary narrowing
caused by nonocclusive thrombus formation subsequent to disruption of an atherosclerotic
plaque. In contrast, STEMI results from an occlusive thrombus. Each year, more than 5
million patients present to U.S. emergency departments with chest pain and related
symptoms.1 Approximately 1.4 million of these patients are admitted for management of
UA/NSTEMI.1 Because of the scope of the problem, it is important for family physicians to
understand the diagnosis, risk assessment, and treatment of this syndrome.

To help standardize the assessment and treatment of patients with UA/NSTEMI, the
American College of Cardiology (ACC) and the American Heart Association (AHA)
convened a task force to produce a management guideline. The ACC/AHA guideline, which
was published in 20001 and updated in 2002,2,3  divides the management of suspected
UA/NSTEMI into four components: initial evaluation and management; hospital care;
coronary revascularization; and hospital discharge and post-hospital care.

ACC/AHA Classification of Evidence Used in the UA/NSTEMI Guideline

Class I: conditions for which there is evidence or general agreement that a given procedure or
treatment is useful and effective
Class II: conditions for which there is conflicting evidence or a divergence of opinion about the
usefulness or efficacy of a procedure or treatment

Class IIa: weight of evidence or opinion favors usefulness or efficacy

Class IIb: usefulness or efficacy is less well established by evidence or opinion

Class III: conditions for which there is evidence or general agreement that a given procedure or
treatment is not useful or effective, and in some cases may be harmful

High-Risk Indicators Favoring an Early Invasive Strategy in Patients with UA/NSTEMI

Recurrent angina or ischemia at rest or with low-level activity, despite intensive anti-ischemic therapy

Elevated cardiac-specific troponin level (troponin I or T)

New or presumably new ST-segment depression

Recurrent angina or ischemia with symptoms of congestive heart failure, an S3 gallop, pulmonary
edema, worsening rales, or new or worsening mitral regurgitation

High-risk findings on noninvasive stress testing

Depressed left ventricular function (e.g., ejection fraction < 40% on noninvasive study)

Hemodynamic instability

Sustained ventricular tachycardia

Percutaneous coronary intervention within previous six months

Previous coronary artery bypass grafting

ANTI-ISCHEMIC THERAPY

ACC/AHA class I anti-ischemic interventions include supplemental oxygen, sublingually or

intravenously administered nitroglycerin for relief of recurrent ischemia and associated
symptoms and, in the absence of contraindications, an intravenously administered beta
blocker for management of ongoing chest pain followed by an orally administered beta
blocker.2,3 Beta blockers should be used cautiously in patients with marked first-degree
atrioventricular block, second- and third-degree atrioventricular block without a pacemaker,
asthma, severe left ventricular dysfunction with congestive heart failure, significant chronic
obstructive pulmonary disease, and significant sinus bradycardia or hypotension.2,3

ANTIPLATELET THERAPY

Three classes of antiplatelet agents have important roles in the management of UA/NSTEMI:
aspirin, thienopyridines, and platelet glycoprotein IIb/IIIa inhibitors.

Aspirin

A cornerstone of management in acute coronary syndromes, aspirin has been shown to reduce
cardiovascular events by 50 to 70 percent.16 In the absence of known contraindications,
aspirin therapy should be used in all patients with suspected, probable, or definite acute
coronary syndrome.

Clopidogrel

The updated ACC/AHA guideline2,3 recommends use of the thienopyridine clopidogrel

(Plavix) in patients who cannot tolerate aspirin17 (ACC/AHA class I). Because of its safety
profile (compared with ticlopidine [Ticlid]), clopidogrel currently is the preferred
thienopyridine.1 Clopidogrel is a potent antiplatelet agent that acts by irreversibly blocking
the P2Y12 adenosine diphosphate receptor on the platelet surface, thereby interrupting
platelet activation and aggregation.

One of the major changes in the care of patients with UA/NSTEMI has been the ACC/AHA
class I indication for use of clopidogrel in addition to aspirin in patients with acute coronary
syndromes.2,3 This change occurred because of the findings of recent major clinical trials. The
Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE)
trial18 randomized more than 12,000 patients with UA/NSTEMI to receive clopidogrel or
placebo in addition to aspirin. Patients were followed for three to 12 months. In the CURE
trial, death, myocardial infarction, or stroke occurred in 9.3 percent of the patients treated
with clopidogrel, compared with 11.5 percent of those who received placebo. The
improvement occurred at the cost of a small, but significant increase in bleeding (relative
risk: 27 percent), especially in patients who underwent coronary artery bypass grafting within
five days of discontinuing clopidogrel therapy.

In an analysis of patients undergoing percutaneous coronary intervention (PCI-CURE

study),19 patients were treated with clopidogrel or placebo for a median of 10 days before the
intervention (all patients also received aspirin). After the intervention, patients in the PCI-
CURE study received open-label clopidogrel or ticlopidine for four weeks, followed by the
initial study drug (clopidogrel or placebo) for an average of eight months. The clopidogrel-
treated patients had fewer early (30-day) and long-term cardiovascular events.

As a result of the study findings, the 2002 ACC/AHA guideline2,3 considers the use of
clopidogrel in addition to aspirin to have a class I indication in patients with UA/NSTEMI
who are undergoing an early noninterventional or interventional approach and are not at high
risk for bleeding. Clopidogrel therapy is recommended for at least one month and may be
continued for up to nine months. Aspirin, unless contraindicaetd, should be continued for life.
When elective coronary artery bypass grafting is planned, clopidogrel should be withheld for
five to seven days.

Platelet Glycoprotein IIb/IIIa Inhibitors

These agents constitute a third class of antiplatelet agents that may be used in patients
hospitalized with UA/NSTEMI. Three agents in this class currently are available for clinical
use: abciximab (ReoPro), which is a monoclonal anti-body; and eptifibatide (Integrelin) and
tirofiban (Aggrastat), which are “small molecule” glycoprotein IIb/IIIa inhibitors. These
potent inhibitors of platelet aggregation are administered intravenously.

Clinical trials have shown that platelet glycoprotein IIb/IIIa inhibitor therapy is beneficial in
selected patients with UA/NSTEMI.20 However, benefit appears to be greater in patients for
whom an early invasive strategy is planned (i.e., cardiac catheterization and percutaneous
coronary intervention)20,21 and patients who have elevated cardiac-specific troponin levels22 or
other high-risk indicators such as an elevated TIMI risk score9 or diabetes mellitus.23 In
patients for whom an early invasive strategy is not planned, the Global Utilization of
Strategies to Open Occluded Coronary Arteries IV–Acute Coronary Syndromes (GUSTO IV-
ACS) randomized trial24 showed no benefit for abciximab compared with placebo. As a result
of the GUSTO IV-ACS study findings, use of abciximab is contraindicated in patients for
whom an early invasive strategy is not planned (ACC/AHA class III).

Based on the combined study findings,20–23,25 platelet glycoprotein IIb/IIIa inhibitors have an

ACC/AHA class I indication in patients for whom catheterization and percutaneous coronary
intervention are planned. These agents should be administered in addition to aspirin and
heparin. An ACC/AHA class IIa recommendation is given to the use of eptifibatide or
tirofiban in addition to aspirin and heparin in patients with continuing ischemia, elevated
cardiac-specific troponin levels, or other high-risk features for whom an invasive strategy is
not planned.

ANTITHROMBOTIC THERAPY

The final component of medical therapy to consider in patients with UA/NSTEMI is

antithrombotic/anticoagulant therapy. Unfractionated heparin results in anti-coagulation by
facilitating the action of antithrombin which, in turn, inactivates factor IIa (thrombin), factor
IXa, and factor Xa. Treatment with unfractionated heparin has been shown to be superior to
aspirin therapy alone in patients with UA/NSTEMI.26 Low-molecular-weight (LMW) heparin
(e.g., enoxaparin) is obtained through cleavage of heparin to provide chains with different
molecular weights. Compared with unfractionated heparin, the LMW heparins are relatively
more potent inhibitors of factor Xa. LMW heparins also have a more predictable
pharmacology, which means that laboratory monitoring of anticoagulation status is not
needed.26 Anticoagulation with unfractionated heparin or LMW heparin has an ACC/AHA
class I indication.27 One of these agents is to be used in addition to aspirin or clopidogrel.

Recent trial data28 have shown superior results with the use of enoxaparin compared with
unfractionated heparin in patients with UA/NSTEMI. Consequently, the guideline2,3 indicates
a ACC/AHA class IIa recommendation for the use of enoxaparin, rather than unfractionated
heparin, in patients with UA/NSTEMI. Although data are not conclusive, recent trials have
shown that LMW heparin is safe to use in combination with glycoprotein IIb/IIIa
inhibitors29,30 and in percutaneous coronary intervention.31–33
Despite the role of thrombosis in UA/NSTEMI, thrombolytic agents have not been shown to
provide benefit in patients with UA/NSTEMI; in fact, there is a trend toward worse
outcomes.34–36 Consequently, thrombolytic agents are contraindicated for use in the treatment
of patients who have UA/NSTEMI.

Sumber : https://www.aafp.org/afp/2004/0801/p525.html

 Pathogenesis and pathophysiology ACS

Pathophysiology
The underlying pathophysiology in ACS is decreased blood flow to part of heart musculature
which is usually secondary to plaque rupture and formation of thrombus. Sometimes ACS
can be secondary to vasospasm with or without underlying atherosclerosis. The result is
decreased blood flow to a part of heart musculature resulting first in ischemia and then
infarction of that part of the heart.

History and Physical

The classic symptom of ACS is substernal chest pain, often described as crushing or
pressure-like feeling, radiating to the jaw and/or left arm. This classic presentation is not seen
always, and the presenting complaint can be very vague and subtle with chief complaints
often being difficulty breathing, lightheadedness, isolated jaw or left arm pain, nausea,
epigastric pain, diaphoresis, and weakness.  Female gender, patients with diabetes, and older
age are all associated with ACS presenting with vague symptoms. A high degree of suspicion
is warranted in such cases.
In the physical exam, general distress and diaphoresis are often seen. Heart sounds are
frequently normal. At times, gallop and murmur can be heard. Lung exam is normal, although
at times crackles may be heard pointing toward associated congestive heart failure (CHF).
Bilateral leg edema may be present indicating CHF. The rest of the systems are typically
within normal limits unless co-pathologies are present. The presence of abdominal tenderness
to palpation should make the provider consider other pathologies like pancreatitis and
gastritis. The presence of unequal pulses warrants consideration of aortic dissection. The
presence of unilateral leg swelling should warrant work-up for pulmonary emboli. Hence a
thorough physical exam is very important to rule out other life-threatening differentials.

Evaluation
The first step of evaluation is an ECG, which helps differentiate between STEMI and
NSTEMI unstable angina. American Heart Association guidelines maintain that any patient
with complaints suspicious of ACS should get an ECG within 10 minutes of arrival. Cath lab
should be activated as soon as STEMI is confirmed in a percutaneous coronary intervention
(PCI) center. Cardiac enzymes especially troponin, CK-MB/CK ratio is important in
assessing the NSTEMI versus myocardial ischemia without tissue destruction. A chest x-ray
is useful in diagnosing causes other than MI presenting with chest pain like pneumonia and
pneumothorax. The same applies for blood work like complete blood count (CBC),
chemistry, liver function test, and lipase which can help differentiate intraabdominal
pathology presenting with chest pain. Aortic dissection and pulmonary emboli should be kept
in differential and investigated when the situation warrants. 
Sumber : https://www.ncbi.nlm.nih.gov/books/NBK459157/

 Kenapa bisa rupture, kenapa bisa terbentuk thrombus. Apa yg terjadi sama
myocyte ( early and late changes of infarction), kapan reversible kapan
irreversible

A cascade of events leads to plaque rupture. Accumulation of lipid in the lesion leads to
dramatically increased stress on the fibrous cap of the lesion. In addition, lipid acccumulation
promotes inflammation through chemotactic factors and upregulation of adhesion molecules.
The combination of increased mechanical stress on the fibrous cap and weakening of the
fibrous cap extracellular matrix leads to plaque rupture.
Coronary artery thrombus occurs due to rupture or erosion of preexisting coronary artery
plaque, resulting in the artery's complete occlusion. [1] It manifests clinically as an acute
coronary syndrome, including ST-elevation MI, Non-ST elevation myocardial infarction, and
unstable angina[2]. The coronary thrombus can occur in both symptomatic and asymptomatic
patients with significant or less than 50% stenosis. Coronary thrombus is one of the frequent
causes of sudden cardiac death[3][4]. The literature review shows that coronary thrombus
causes one-third of the sudden cardiac death, complete occluding the culprit artery on
autopsy. The amount and duration of coronary thrombus play an essential role in determining
the prognosis of ACS patients. [5] The coronary thrombus has a crucial impact on
percutaneous coronary intervention's performance and outcome (PCI). [6] It is a strong
predictor of PCI-induced major adverse coronary events, distal embolization, and stent
thrombosis. [7] This chapter will review etiology, epidemiology, pathophysiology,
histopathology, history and physical examination, treatment, differential diagnosis, staging,
and prognosis of coronary thrombus.

Etiology
The risk factors involved in coronary thrombus initiation include smoking, diabetes mellitus,
hypertension, hyperlipidemia, stress, and family history of atherosclerosis.
Epidemiology
Coronary thrombosis with acute myocardial infarction is a life-threatening condition and
associated with increased morbidity and mortality globally.[8] Coronary thrombus causes
death in 200,000 persons a year in the United States, affecting males more than females

Pathophysiology
Understanding the structure of thrombus and its physical characteristics are essential to make
proper treatment choices in the revascularization of atherosclerotic lesions. [9] Following the
rupture of the plaque's fibrous cap, the internal necrotic core becomes exposed to the arterial
lumen. This contact of a highly thrombogenic subendothelial matrix with the circulating
platelets and white blood cells activates the coagulation cascade. It activates the platelets and
promotes their adhesion and aggregation. Activated platelets release strong mediators of
vasoconstriction and aggregation like serotonin, adenosine diphosphate (ADP), thromboxane
A2 (TXA2), and endothelin, among others. The released tissue factor from the subendothelial
matrix directly activates the extrinsic coagulation cascade and results in fibrin accumulation.
All this finally accumulates to form a thrombus, which causes acute occlusion and impaired
distal flow, with resultant clinical ischemic complications. [10] A thrombus comprises a
conglomerate of platelets, red blood cells, vasoconstrictors, and procoagulant anchored to a
scaffolding matrix of crisscrossing fibrin fibers. Two distinct types of branching fibrin fibers
exist. The dense, thin fibers resist deforming mechanical forces and are poorly dissolve by
thrombolytic agents. Thick fibrin fibers are susceptible to external mechanical forces and get
dissolved by thrombolytic agents.[11][12]

Histopathology
A thrombus comprises a conglomerate of platelets, red blood cells, vasoconstrictors, and
procoagulant anchored to a scaffolding matrix of crisscrossing fibrin fibers. Two distinct
types of branching fibrin fibers exist. The dense, thin fibers resist deforming mechanical
forces and are poorly dissolve by thrombolytic agents. Thick fibrin fibers are susceptible to
external mechanical forces and get dissolved by thrombolytic agents.

Staging
Grading systems are essential for the adequate assessment of thrombus burden to assist
management decisions before and during interventions. The TIMI Study Group introduced
the most commonly used thrombus grading classification. Their method based on a visual
angiographic assessment of the thrombus size using a score that ranges from grade 0 to grade
5. [29]
 Grade 0: No angiographic characteristic of thrombus
 Grade 1: Possibility of thrombus on angiography, decreased density, haziness,
irregular lesion contour
 Grade 2: Definite thrombus, significant filling defects, the greatest dimension is 1/2 of
vessel diameter
 Grade 3: Definite thrombus with the greatest dimension is greater than 1/2 to less than
2 vessel diameter
 Grade 4: Definite large thrombus with the greatest dimension is greater than 2 vessel
diameter
 Grade 5: Complete thrombotic occlusion
Sumber : https://www.ncbi.nlm.nih.gov/books/NBK534808/

2. Describe clinical features of acute coronary syndromes

 Sumber : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755812/

3. Define the role of ECG in diagnosis in myocardial ischemia and acute coronary
syndrome

Recording an ECG during an episode of the presenting symptoms is valuable. Transient ST-
segment changes (>0.05 mV) that develop during a symptomatic period and that resolve
when the symptoms do are strongly predictive of underlying CAD and have prognostic value.
Comparison with previous ECGs is often helpful.
Alternative causes of ST-segment and T-wave changes are left ventricular aneurysm,
pericarditis, Prinzmetal angina, early repolarization, Wolff-Parkinson-White syndrome, and
drug therapy (eg, with tricyclic antidepressants, phenothiazines).
In the emergency setting, ECG is the most important ED diagnostic test for angina. It may
show changes during symptoms and in response to treatment, confirm a cardiac basis for
symptoms. It also may demonstrate preexisting structural or ischemic heart 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 episodes include the following:
 Transient ST-segment elevations
 Dynamic T-wave changes - Inversions, normalizations, or hyperacute changes
 ST depressions - May be junctional, downsloping, or horizontal
In patients with transient ST-segment elevations, consider LV aneurysm, pericarditis,
Prinzmetal angina, early repolarization, and Wolff-Parkinson-White syndrome as possible
diagnoses. Fixed changes suggest acute myocardial infarction.
When deep T-wave inversions are present, consider the possibility of central nervous system
(CNS) events or drug therapy with tricyclic antidepressants or phenothiazines as the cause.
Diagnostic sensitivity may be increased by performing right-sided leads (V 4 R), posterior
leads (V8, V9), and serial recordings.

Sumber : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391175/

4. Define the role of cardiac enzymes in diagnosis of Acute Myocardial Infarction

Cardiac enzymes have been in use since the mid 20th century in evaluating patients with
suspected acute myocardial infarction (MI). The biomarkers used back then are not clinically
relevant today as more sensitive and specific biomarkers have replaced them. Troponins are
the most widely recognized and important cardiac enzymes used in the diagnosis of acute
myocardial ischemia in modern medicine. The majority of patients with an acute MI will
have elevation in troponins within 2 to 3 hours of arrival at the emergency department, versus
6 to 12 hours with creatine kinase.

Diagnostic Tests
The first biomarker used to aid in the diagnosis of acute MI was aspartate aminotransferase
(AST). In 1954, Ladue et al. proposed that AST released from cardiomyocytes undergoing
necrosis would be useful in diagnosing acute MI.[1] AST increases in the blood 3 to 4 hours
after an acute MI, peaks at 15 to 28 hours and returns to baseline within 5 days. In current
clinical practice, AST has fallen out of favor for diagnosing acute MI because it is not a
specific marker for cardiac myocytes. AST levels in the blood elevate in hepatic disease (e.g.,
hepatitis, hepatic congestion), pericarditis, pulmonary embolism, and shock and as a result, is
not used in the diagnosis of acute MI anymore.
After discovering that AST was released from ischemic cardiac myocytes, lactate
dehydrogenase (LDH) emerged as another potential biomarker for detecting myocardial
ischemia. LDH increases in the blood 6 to 12 hours after an acute MI, peaks within 24 to 72
hours and normalizes within 8 to 14 days. In the past, a ratio of LDH1 (an isoform found in
the heart) to LDH2 greater than 1 was considered to be specific for an acute MI.[2] Since it is
not a specific marker for cardiac myocytes, and its levels can also increase in many other
conditions, LDH is no longer used in the diagnosis of myocardial infarction. Nowadays, the
only usage for LDH in the evaluation of acute MI is to differentiate acute from subacute MI
in patients with elevated troponin levels and normal creatine kinase (CK) and CK-MB levels.
[3] Blood LDH levels are still valuable for detecting erythrocyte hemolysis and for evaluating
the management and prognosis of certain tumors such as testicular germ cell tumors.[4] 
Myoglobin is a heme protein found in cardiac and skeletal muscle tissue. Due to its low
molecular weight, myoglobin can be detected in the blood 1 hour after myocardial injury,
peaks within 4 to 12 hours, and then immediately return to baseline levels.[5] As a result, it
had some diagnostic value alongside CK-MB for faster detection of acute MI. Although
troponins have largely replaced myoglobin in the detection of acute MI, myoglobin is still
valuable in the evaluation of skeletal muscle injury due to rhabdomyolysis.
Heart-type fatty acid-binding protein (H-FABP) is a protein involved in fatty acid metabolism
in cardiac myocytes. In a study by Kabekkodu et al., the sensitivity of H-FABP in detecting
acute MI in patients who present within 4 hours of the onset of symptoms was 60%, which
was significantly higher than that of troponin (18.8%) and CK-MB (12.5%). The sensitivity
of H-FABP in detecting acute MI between 4 to 12 hours after symptom onset was 86.96%,
which was comparable to troponin (90.9%) and higher than CK-MB (77.3%).[6] However, it
is also important to note that the specificity of H-FABP in detecting acute MI was less than
that of troponin and CK-MB.[6] Despite its high sensitivity in detecting myocardial ischemia,
H-FABP is not clinically used in the United States and has yet to undergo rigorous testing
against high sensitivity troponin assays. (hs-TnT). Thus, H-FABP is not suitable as a stand-
alone test for diagnosing acute MI but may have some value as an adjunctive test in specific
patient populations.
CK-MB still holds some diagnostic value in cardiac and non-cardiac conditions. CK-MB is
detected in the serum 4 hours after myocardial injury, peaks by 24 hours, and normalizes
within 48 to 72 hours. CK-MB is a useful biomarker for detecting acute MI as it has a relative
specificity for cardiac tissue but can still become elevated in non-cardiac conditions such as
skeletal muscle injury, hypothyroidism, chronic renal failure, and severe exercise. The ratio
of CK-MB2 to CK-MB1 greater than or equal to 1.5 and a CK-MB relative index (CK-
MB/total CK x 100) greater than or equal to 2.5 improve specificity for cardiac tissue and are
indicative of acute MI.[7] Since CK-MB normalizes 48 to 72 hours after myocardial ischemia
(vs. troponins, which can persist for days), it can be useful in detecting re-infarction if levels
rise again after declining.
Cardiac troponin is currently the first-line test for evaluating patients with suspected acute
MI. Troponin is a protein found in both cardiac and skeletal muscles that play a role in
muscle contraction. It is comprised up of three subunits, troponin C, troponin I and troponin
T. Troponin I and troponin T in the heart are structurally different than the ones found in
skeletal muscle, making them specific and sensitive biomarkers of cardiac myocyte injury. As
a result, the European Society of Cardiology and American College of Cardiology guidelines
released in September 2000, defined acute MI as an elevation in serum troponin greater than
the level that expected from the 99 percentile of a healthy reference population supported by
signs and symptoms of cardiac ischemia.[8] This was also corroborated by the 2007 World
Task Force definition of MI, which stated that acute MI is accurately determined based on at
least one troponin value over the 99th percentile of the upper reference limit in tandem with
signs and symptoms of cardiac ischemia, electrocardiogram changes, and/or imaging findings
suggestive of wall motion abnormalities or the loss of viable myocardium.[9] Troponin T and
troponin I levels in the blood rise as early as 4 hours from the onset of acute MI symptoms,
peaks in 24 to 48 hours, and remain elevated for multiple days thereby making them useful
for detecting initial ischemic events but not reliable to detect re-infarction.[10] High-
sensitivity troponin assay (hs-TnT), a test developed to detect troponin at much lower
concentrations than what the conventional troponin tests can detect, allows for more
rapid diagnosis in patients admitted to the hospital suspected to have acute MI. In a Japnese
multicenter study, hs-TnT was found to have superior diagnostic value, compared to other
cardiac biomarkers, in diagnosing acute MI within the first 3 hours of admission in patients
with negative initial troponin T levels. Researchers also noted that this test
had 100% sensitivity and negative predictive value in diagnosing acute MI, but the specificity
was limited.[11]

Interfering Factors
Cardiac troponins are the standard, first-line blood test used to diagnose acute MI. However,
cardiac troponins may be elevated in cases unrelated to cardiac ischemia. Elevated levels of
cardiac troponins can occur due to open-heart surgery, post percutaneous coronary
intervention, acute pulmonary embolism, end-stage renal disease, pericarditis, myocarditis,
Stanford A aortic dissection, acute or chronic heart failure, strenuous exercise, cardiotoxic
chemotherapy, radiofrequency catheter ablation of arrhythmias, cardioversion of atrial
fibrillation or atrial flutter, defibrillation for ventricular fibrillation or tachycardia,
amyloidosis, cardiac contusion from blunt chest wall trauma, sepsis, and rhabdomyolysis.
[12] Another study has shown that aortic valve disease, apical balloon syndrome,
bradyarrhythmia, endomyocardial biopsy, hypertrophic cardiomyopathy, tachyarrhythmias
and non-cardiac causes such as acute pulmonary edema, chronic obstructive pulmonary
disease, pulmonary hypertension, stroke, and subarachnoid hemorrhage can also cause
cardiac troponins to become elevated in the blood.[7] These conditions may increase cardiac
troponin concentration in the blood due to a mismatch between cardiac oxygen supply and
demand even in the absence of coronary artery disease. 
The diagnosis of myocardial infarction requires that cardiac troponin levels must be above
the 99 percentile upper reference limit for the assay in use and that there is clinical evidence
of myocardial ischemia. Thus an elevated cardiac troponin level in the blood without clinical
evidence of myocardial ischemia (e.g., symptoms of acute MI, ECG abnormalities, wall
motion abnormalities) should prompt a search for other underlying conditions.

Results, Reporting, Critical Findings

Current recommendations recommend that troponin testing should be available in all
hospitals 24/7 with a turnaround time of 60 minutes.
In addition to its application as a diagnostic marker for MI, elevated levels of troponin also
have prognostic significance; high levels suggest an elevated risk for adverse cardiac events.
Further, data show that increasing levels of troponin and creatinine are strong predictors of
worsening of congestive heart failure.

Clinical Significance
Cardiac troponins are specific and sensitive biomarkers of cardiac ischemia, and they are the
preferred blood test in the evaluation of patients suspected to have acute MI. There
are sensitive and highly sensitive assays to detect cardiac troponin levels in the blood. The
highly sensitive troponin assay obtained approval for use in the USA in 2017. Although CK-
MB has a high sensitivity for cardiac myocytes, it should not be used as a first-line diagnostic
test if cardiac troponin assays are available. In the absence of cardiac troponin assays, CK-
MB can be useful in the evaluation of acute MI, but it is far less sensitive and specific than
cardiac troponins. Since cardiac troponin levels remain elevated in the blood for multiple
days after an acute MI, they are not useful in evaluating for re-infarction of cardiac myocytes
(another MI). CK-MB levels normalize 48 to 72 hours after an acute MI, so a rising level in
the blood after normalization can confirm that another MI has occurred.
Clinicians need to understand that cardiac markers are not mandatory in patients who present
with acute chest pain mimicking angina and ECG evidence of ST-segment elevation. These
individuals are candidates for primary coronary intervention or thrombolytic therapy. One
should not delay treatment waiting for cardiac markers because their sensitivity is not high in
the early hours after an infarct.

Enhancing Healthcare Team Outcomes

The correct diagnosis of acute MI requires an interprofessional team of healthcare
professionals that includes laboratory technologists, nurses, and physicians. Measuring the
blood levels of cardiac troponins is one of the first steps in reaching a diagnosis. Swift
diagnosis of acute MI is crucial, as the less the time from symptom onset to reperfusion
therapy is vital for improved long-term outcome of heart function.[13] The path to diagnosing
acute MI starts with the physician ordering a cardiac troponin blood test, the nurses drawing
blood and sending it to the appropriate laboratory and the laboratory technologists accurately
measuring blood titers of cardiac troponins and posting the result on the electronic medical
records.
Sumber : https://www.ncbi.nlm.nih.gov/books/NBK545216/
Cardiac enzymes ― also known as cardiac biomarkers ― include myoglobin, troponin and

creatine kinase.

Historically, lactate dehydrogenase, or LDH, was also used but is non-specific. Cardiac

enzymes are released into the circulation when myocardial necrosis occurs, as seen in

myocardial infarction.

Myoglobin

Myoglobin is released into circulation with any damage to muscle tissue, including

myocardial necrosis. Because skeletal muscle contains myoglobin, this measurement is quite

nonspecific for MIs. The benefit in myoglobin is that a detectable increase is seen only 30

minutes after injury occurs, unlike in troponin and creatine kinase, which can take between 3

and 4 hours.

Troponin

The enzymes troponin I and troponin T are normal proteins that are important in the

contractile apparatus of the cardiac myocyte. The proteins are released into the circulation

between 3 and 4 hours after myocardial infarction and remain detectable for 10 days

following. This long half-life allows for the late diagnosis of MI but makes it difficult to

detect re-infarction, as can occur in acute stent thrombosis after percutaneous coronary

intervention, or PCI. There are a number causes for troponin elevation not related to

myocardial infarction; however, troponin elevation is much more sensitive than myoglobin

and even creatine kinase.

Creatine kinase (CK)

Creatine kinase ― also known as creatine phosphokinase, or CPK ― is a muscle enzyme that

exists as isoenzymes. The MB type is specific to myocardial cells, whereas MM and BB are

specific to skeletal muscle and brain tissue, respectively. The CK level increases

approximately 3 to 4 hours after MI and remains elevated for 3 to 4 days. This makes it

useful for detecting re-infarction in the window of 4 to 10 days after the initial insult;

troponin remains elevated for 10 days, making it less useful for this purpose.

5. Define clinical management of ischemic heart disease

TREATMENT
Comprehensive management of angina and stable CHD entails multiple therapeutic
approaches, including the following:
 Identification and treatment of associated diseases that can precipitate or worsen
angina and ischemia;
 Cardiac risk factor identification and intervention;
 Application of pharmacological and nonpharmacological interventions for secondary
prevention;
 Pharmacological and symptomatic management of angina and ischemia; and
 Myocardial revascularization with PCI or CABG surgery, when indicated.
A multidimensional management approach integrates all of these considerations, often
simultaneously, in each patient. Among pharmacotherapies, three drug classes have been
demonstrated to reduce mortality and morbidity in patients with stable CHD and preserved
left ventricular (LV) function: aspirin, angiotensin-converting enzyme (ACE) inhibition, and
effective lipid lowering. Beta-blockers have been shown to reduce mortal ity in patients with
prior MI (CAPRICORN Investigators, 2001). Other therapies such as nitrates, beta-blockers,
calcium channel blockers, and ranolazine have been shown to improve angina and exercise
performance and to reduce ischemia, but have not been proven to reduce mortality in patients
with stable CHD.
Clinical practice guidelines for the diagnosis and treatment of chronic stable angina (Fraker et
al., 2007; Gibbons et al., 2002a), unstable angina/non-ST-segment elevation myocardial
infarction (Anderson et al., 2007), and ST-segment elevation myocardial infarction (Antman
et al., 2004; Kushner et al., 2009), have been jointly published by AHA and the American
College of Cardiology (ACC). These guidelines detail the indications and timing of medical
therapy (including lifestyle modification) and revascularization with PCI and/or CABG
(Eagle et al., 2004) and provide guidance for secondary prevention that includes risk factor
reduction (Smith et al., 2006). Although revascularization has specific indications, treatment
with medical therapy, lifestyle modification, and risk factor reduction is recommended across
the spectrum of CHD in both stable and unstable patients and following a coronary event or
revascularization.

Recent Advances
The most recent advance in medical therapy consists of the introduction of ranolazine
(Chaitman, 2006; Chaitman et al., 2004; Morrow et al., 2007). Nonpharmacologic treatments
include spinal cord stimulation (Taylor et al., 2009) and enhanced external counterpulsation
(EECP) (Akhtar et al., 2006; Michaels et al., 2004; Soran et al., 2006) for the treatment of
angina and ischemia. Advances in revascularization include development of drug-eluting
stents (Novack et al., 2009), the introduction of percutaneous support devices in patients
undergoing PCI (Goldstein et al., 1998), and increased use of off-pump techniques, as well as
minimal access and robotic procedures in patients undergoing CABG (Poston et al., 2008;
Sabik et al., 2002). Interest and experience also have been growing in the performance of
hybrid revascularization procedures (Stahl et al., 2002) using a collaborative approach
between interventional cardiologists and cardiothoracic surgeons.
Ranolazine is the newest antianginal agent approved by the Food and Drug Administration
and the first new drug class for angina since calcium channel blockers (CCBs) were
introduced 30 years ago. Ranolazine acts by reducing intracellular calcium overload in
ischemic myocytes by inhibiting late inward sodium current entry. The net effect of reduced
late inward sodium current is a reduction in LV wall tension and myocardial oxygen demand,
thereby reducing angina and ischemia. Ranolazine increases exercise tolerance in patients
with stable angina, reduces episodes of recurrent ischemia, and provides additional
antianginal benefit in patients who are already on intensive antianginal therapy with beta-
blockers and CCBs. While multiple nonspecific side effects of ranolazine have been reported,
the drug is well tolerated in clinical practice. The most common side effects are dizziness (6.2
percent), headache (5.5 percent), constipation (4.5 percent), and nausea (4.4 percent), which
are more commonly observed at the 1,000 mg twice a day dose. Mean QT prolongation noted
in clinical trials ranges from 6 to 8 milliseconds; the clinical relevance of the modest QT
prolongation that occurs in a dose-related manner is unclear, but there has been no increased
risk of a serious proarrhythmic effect (torsades de pointes) or sudden cardiac death reported
in a large, placebo-controlled trial of more than 6,500 patients (MERLIN Trial) (Morrow et
al., 2007).
EECP is an alternative treatment for patients with refractory angina. It is generally
administered as 35 sequential treatments (1 hour daily; 5 days per week) over 7 weeks. EECP
was shown to increase the time to ST-segment depression during exercise testing, reduce
angina, and improve health-related quality of life for at least 1 year in a randomized, double-
blind study of patients with chronic stable angina (Soran et al., 2006). EECP does not reduce
ischemia on myocardial perfusion imaging, and the mechanisms underlying its effects are
poorly understood.

Side Effects of Treatments

Nitroglycerin and nitrates can cause vasodilation-induced headache, a decrease in blood
pressure, and, more rarely, severe hypotension with bradycardia. The vasodilation by
nitroglycerin may be markedly exaggerated and prolonged in the presence of the
phosphodiesterase inhibitors sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), so
these agents should not be used concurrently with nitrates.
Most of the adverse effects of beta-blockers occur as a consequence of the known properties
of these drugs and include cardiac effects (e.g., severe sinus bradycardia, sinus arrest, reduced
LV contractility), bronchoconstriction, fatigue, mental depression, nightmares,
gastrointestinal upset, sexual dysfunction, intensification of insulin-induced hypoglycemia,
and cutaneous reactions. Lethargy, weakness, and fatigue may be caused by reduced cardiac
output or may arise from a direct effect on the central nervous system. Bronchoconstriction
results from blockade of beta2 receptors in the tracheobronchial tree. As a consequence,
reversible obstructive lung disease (e.g., asthma) may be considered as relative
contraindications to beta-blockers, even to beta1-selective agents (Egred et al., 2005).
Calcium channel blockers are potent vasodilators, which may lead to dizziness, hypotension,
and reflex tachycardia—particularly with some dihydropyridines. Peripheral edema can
occur, usually with the dihydropyri dines. Both verapamil and diltiazem can cause
bradycardia or conduction disturbances, particularly if coadministered with beta-blockers.
Diltiazem and verapamil may exacerbate or precipitate heart failure in patients with reduced
LV ejection fraction.

Trends in Morbidity and Mortality

Data from the Framingham Heart Study showed the overall death rates from CHD decreased
by 64 percent from 1950 to 1999. From 1996 to 2006, the annual death rate due to CHD
declined by 36.4 percent, and the actual number of deaths declined by 21.9 percent (Lloyd-
Jones et al., 2010). An analysis of NHANES CHD mortality data between 1980 and 2000
revealed that approximately 47 percent of the decline in mortality could be explained by the
use of medical and surgical treatment (including secondary prevention therapies after
myocardial infarction or revascularization, initial treatment of MI or unstable angina,
treatment of heart failure, revascularization for chronic angina, and other therapies, including
antihypertensive and lipid-lowering primary prevention strategies), whereas approximately
44 percent of the mortality decline was attributed to changes in risk factors (including lower
total cholesterol, systolic blood pressure, and smoking prevalence, and decreased physical
inactivity) (Lloyd-Jones et al., 2010).
According to data from the National Registry of Myocardial Infarction, in-hospital mortality
following acute MI declined from 11.2 percent in 1940 to 9.4 percent in 1999 (Lloyd-Jones et
al., 2010). Moreover, a recent analysis of the Medicare fee-for-service population revealed
that the adjusted hospitalization rate for acute MI declined by 5.8 percent per year from 2002
through 2007, although there was a slower rate of decline in African American patients
compared with white patients
Sumber : https://www.ncbi.nlm.nih.gov/books/NBK209964/

6. Define clinical management of acute coronary syndrome

UNSTABLE ANGINA/NSTEMI
The 2007 ACC/AHA guidelines state that the goal of immediate treatment of patients with
UA/NSTEMI is to provide relief of ischemia and to prevent the recurrence of adverse
ischemic events.42 Treatment with anti-ischemic, antiplatelet, and anticoagulant agents is
fundamental to achieving this goal. In addition to aggressive medical therapy, 2 treatment
pathways have emerged for treating UA/NSTEMI patients: an early invasive strategy and an
initial conservative strategy. Risk stratification helps to determine how aggressive we should
be with respect to both medical therapy (Table 5) and treatment strategy.
TABLE 5.
Class I Recommendations for Anti-Ischemic Therapy

Early Invasive Strategy or Initial Conservative Strategy

An early invasive strategy involves routine cardiac catheterization, generally within 4 to 24
hours after admission, followed by revascularization with percutaneous coronary intervention
(PCI) or coronary artery bypass grafting (CABG), as appropriate, depending on the coronary
anatomy. A conservative strategy, in contrast, consists of initial medical management,
followed by catheterization and revascularization only if ischemia recurs despite vigorous
medical therapy, either when the patient is at rest or during a noninvasive stress test. The
2007 ACC/AHA guidelines have given the early invasive strategy a class I, level of evidence
A recommendation for patients with UA/NSTEMI who are at high risk (Table 6).42 The
guidelines recommend either a conservative or an invasive strategy for low-risk patients
because the outcomes achieved by these approaches are similar for these patients. However,
the guidelines give the conservative strategy a class I recommendation for women with low-
risk characteristics.

TABLE 6.
Selection of Initial Treatment Strategy: Invasive vs Conservative

To date, 10 randomized trials have assessed these 2 general strategies. Although the first 3
trials and the most recent trial found no substantial differences between the strategies in
outcomes, the remaining 6 trials have shown that an early invasive strategy provides
substantial benefits.
The FRISC II (Framingham and Fast Revascularization During Instability in Coronary Artery
Disease II) trial, which involved 2457 patients with UA/NSTEMI, found that the early
invasive strategy achieved a significantly lower rate of the primary end point of death or MI
at 6 months (9.4%) than did the conservative strategy (12.1%; P=.031).89 The TACTICS-
TIMI 18 (Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or
Conservative Strategy—Thrombolysis in Myocardial Infarction 18) trial randomly assigned
2200 patients, who were treated with aspirin, heparin, and tirofiban, to an early invasive or a
conservative strategy.40 At 6 months, the rate of the primary end point of death, MI, or
rehospitalization for ACS was 19.4% for the conservative strategy group and 15.9% for the
early invasive group (odds ratio, 0.78; P=.025).40 Patients with elevated troponin
concentrations, ST-segment changes, and a high TIMI risk score (≥3) derived the most
benefit from the early invasive strategy. The most recent trial, the ICTUS (Invasive Versus
Conservative Treatment in Unstable Coronary Syndromes), randomly assigned 1200 patients
with ACS to an early invasive strategy or a conservative strategy and found no significant
differences between the groups at 1 year90 and at 3 years91 in the rate of the primary end point
of death, MI, or rehospitalization for angina.
A meta-analysis of contemporary randomized trials of treatments for NSTEMI found that the
early invasive strategy was associated with a statistically significant 25% lower incidence of
all-cause mortality than was the conservative strategy (P=.001).92 Another meta-analysis of 8
randomized trials comparing invasive and conservative strategies for women and men with
non—ST-segment elevation ACS found that an early invasive strategy was equally beneficial
for men and for women who were considered to have high-risk disease on the basis of
elevated levels of biomarkers of necrosis.93
A recent randomized trial, the TIMACS (Timing of Intervention in Patients With Acute
Coronary Syndromes), compared the outcomes achieved by an early invasive strategy
(intervention within 24 hours of presentation) and a delayed invasive strategy (intervention at
any time >36 hours after presentation) for 3031 high-risk patients with UA/NSTEMI.94 The
early invasive strategy was not superior to the delayed invasive strategy in reducing the
primary end point of death, MI, or stroke at 6 months (9.6% vs 11.3%; hazard ratio [HR],
0.85; 95% confidence interval [CI], 0.68-1.06; P=.15), except for high-risk patients with a
GRACE risk score higher than 140 (13.9% vs 21.0%; HR, 0.65; 95% CI, 0.48-0.89; P=.006).

ANTI-ISCHEMIC THERAPY
The ACC/AHA class I recommendations for anti-ischemic therapy are listed in Table 5 and
include both nonpharmacological and pharmacological measures.

Nitroglycerin
Nitroglycerin is a vasodilator that reduces myocardial oxygen demand by decreasing
ventricular preload via venodilation; it enhances myocardial oxygen delivery by dilating large
coronary arteries and improving collateral flow to ischemic areas. Nitroglycerin should
initially be given sublingually or by buccal spray (0.3-0.6 mg) every 5 minutes for a total of 3
doses. If pain persists, the administration of intravenous (IV) nitroglycerin should be initiated
(initial rate of 5-10 μg/min with increases of 10 μg/min every 3 to 5 minutes until symptoms
are relieved or if systolic blood pressure falls below 100 mm Hg). Topical or oral nitrates can
be used if the episode of pain has resolved, and they may replace IV nitroglycerin if the
patient has been pain-free for 12 to 24 hours. Absolute contraindications to the use of
nitroglycerin are hypotension or the use of sildenafil within the previous 24 hours or of
tadalafil within the previous 48 hours.95

Morphine and Other Analgesics

Morphine is recommended when ischemia-related symptoms are unrelieved after 3 doses of
nitroglycerin or when such symptoms recur during treatment. In such cases, 1 to 5 mg of
morphine sulfate can be administered intravenously every 5 to 30 minutes as needed, with
careful monitoring of blood pressure and respiratory rate. Morphine acts as a potent analgesic
and anxiolytic; in addition, its hemodynamic effects may be beneficial in treating
UA/NSTEMI. The 2007 ACC/AHA guidelines downgraded the recommendation for the use
of morphine for uncontrolled ischemic discomfort from class I to class IIa because data from
a large observational registry, although subject to uncontrolled selection biases, suggested
that the adjusted likelihood of death was higher when morphine was used.96
The ACC/AHA guidelines state that the use of nonsteroidal anti-inflammatory drugs, both
nonselective agents and cyclooxygenase-2 selective agents (except for aspirin), should be
discontinued when a patient presents with UA/NSTEMI because of the known cardiovascular
risks associated with these agents,97 and also because the EXTRACT-TIMI 25 (Enoxaparin
and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment—Thrombolysis In
Myocardial Infarction 25) trial found that these agents were associated with an increased risk
of adverse cardiovascular events.98

β-Blockers
β-Blockers inhibit β-1 adrenergic receptors in the myocardium and decrease myocardial
contractility and heart rate, thereby reducing myocardial oxygen demand. The 2007
ACC/AHA guidelines state that, in the absence of contraindications, therapy with oral β-
blockers should be initiated within the first 24 hours after onset of ACS (class I
recommendation).42 For all patients, the oral dose should be adjusted to achieve a target
resting heart rate of 50 to 60 beats/min. It is reasonable to administer IV β-blockers to
patients who are hypertensive at the time of presentation (class IIa recommendation). The
COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction) trial found that the risk of
cardiogenic shock was higher for patients treated with intravenous β-blockers than for those
who were not (especially for patients with tachycardia, hypotension, or in Killip class II or III
CHF). Because of this finding, the 2007 ACC/AHA guidelines suggest caution in the use of
IV β-blockers.99 Contraindications to β-blockade include severe sinus bradycardia (heart rate
<50 beats/min), marked first-degree atrioventricular block (ECG P-R interval >0.24 second)
or any second-degree or third-degree atrioventricular block, persistent hypotension,
pulmonary edema, history of bronchospasm, evidence of a low-output state (eg, oliguria), and
increased risk of cardiogenic shock.42 Several placebo-controlled trials involving patients
with UA/NSTEMI have demonstrated the benefit of β-blockers in reducing the incidence of
subsequent MI, recurrent ischemia, or both.100-103

Calcium Channel Blockers

Calcium channel blockers inhibit the contraction of both the myocardium (thereby reducing
myocardial oxygen demand) and the vascular smooth muscle (thereby causing coronary
vasodilatation and improving myocardial blood flow). The ACC/AHA guidelines recommend
these agents for patients with persistent or recurrent symptoms after treatment with full-dose
nitrates and β-blockers, for patients with contraindications to β-blockade, and for patients
with Prinzmetal variant angina.42 For such patients, calcium channel blockers that slow the
heart rate (eg, diltiazem or verapamil) are recommended. These agents should not be
administered to patients with severe LV dysfunction or pulmonary edema.104 DAVIT (Danish
Verapamil Infarction Trial) is the largest randomized trial to date to have evaluated the
efficacy of a calcium channel blocker for patients with ACS. The results showed a trend
toward lower rates of death or MI when verapamil was administered to patients with
suspected ACS.105,106 Similar decreases in the rates of MI and refractory angina have been
found with diltiazem.107 Nifedipine, which does not reduce the heart rate, has been shown to
be harmful to patients with acute MI when it is administered without the simultaneous
administration of a β-blocker.108 The newer dihydropyridine calcium antagonists amlodipine
and felodipine have not been evaluated specifically for administration to patients with ACS,
but trials involving normotensive patients with CAD109 or hypertensive patients with
cardiovascular risk factors110 have demonstrated that these agents provide significant benefits.

Inhibitors of the Renin-Angiotensin-Aldosterone System

The 2007 ACC/AHA guidelines recommend that, in the absence of hypotension or other
known contraindications, an angiotensin-converting enzyme (ACE) inhibitor (or an
angiotensin II receptor blocker for patients who cannot tolerate ACE inhibitors) should be
administered orally within the first 24 hours to patients with pulmonary congestion or an LV
ejection fraction of 40% or lower (class I recommendation) and should be considered for
administration to patients without these features (class IIa recommendation).42 The
recommendation for ACE inhibitor therapy is based on the results of several large trials
showing that mortality rates were substantially reduced when ACE inhibitors were initiated
within 24 hours of MI.111,112 The angiotensin II receptor blocker valsartan was found to be as
effective as captopril for patients at high risk of cardiovascular events after MI; however,
administering a combination of the 2 agents was found to be harmful.113 Long-term use of
ACE inhibitors is indicated for many patients with high-risk chronic CAD.114,115
EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and
Survival Study) found that the selective aldosterone receptor blocker eplerenone reduced
morbidity and mortality rates for patients with MI complicated by LV dysfunction and either
CHF or diabetes mellitus.116 Long-term administration of eplerenone is indicated for such
patients in the absence of severe renal dysfunction or hyperkalemia.42

Other Anti-Ischemic Therapies

Ranolazine is a recently approved anti-ischemic agent that is indicated for use alone or in
combination with nitrates, β-blockers, or amlodipine for the treatment of chronic refractory
angina. The MERLIN-TIMI 36 (Metabolic Efficiency with Ranolazine for Less Ischemia in
Non—ST-Elevation Acute Coronary Syndromes—Thrombolysis in Myocardial Infarction
36) trial demonstrated that ranolazine had a benefit over placebo in reducing the incidence of
recurrent ischemia (HR, 0.87; 95% CI, 0.76-0.99; P=.03) when administered within 48 hours
of the onset of UA/NSTEMI. However, ranolazine had no effect on the composite end point
of cardiovascular death, MI, or recurrent ischemia (HR, 0.92; 95% CI, 0.83-
1.02; P=.11).117,118

ANTITHROMBOTIC THERAPY
Antithrombotic therapy is the cornerstone of treatment for patients with UA/NSTEMI. It has
2 components: (1) antiplatelet therapy, which reduces platelet activation and aggregation,
integral steps in the formation of a thrombus after plaque disruption, and (2) anticoagulant
therapy, which targets the clotting cascade to prevent the deposition of fibrin strands in the
clot. The ACC/AHA guidelines recommend tailoring the specific antithrombotic agents to the
treatment strategy selected. Figure 3 shows the algorithm for choosing agents for patients
managed with an invasive strategy, and Figure 4 shows the algorithm for patients managed
with a conservative strategy.
FIGURE 3.

Algorithm for patients with UA/NSTEMI managed by an initial invasive strategy. When
multiple drugs are listed, they are in alphabetical order and not in order of preference. GP =
glycoprotein; IV = intravenous; LOE = level of evidence; NSTEMI = non—ST-segment
elevation myocardial infarction; UA = unstable angina; UFH = unfractionated heparin.
a
 For full dosing information, see Table 13 in reference 42.
b
 Evidence exists that GP IIb/IIIa inhibitors may not be necessary if the patient received a
preloading dose of at least 300 mg of clopidogrel at least 6 h earlier (class I, LOE: B for
clopidogrel administration) and bivalirudin is selected as the anticoagulant (class IIa, LOE:
B).
c
For more details on management of patients with UA/NSTEMI after diagnostic angiography,
see Figure 9 of reference 42.
From J Am Coll Cardiol,42 with permission from Elsevier.
FIGURE 4.

Algorithm for patients with UA/NSTEMI managed by an initial conservative strategy. When
multiple drugs are listed, they are in alphabetical order and not in order of preference. EF =
ejection fraction; GP = glycoprotein; LOE = level of evidence; LVEF = left ventricular
ejection fraction; NSTEMI = non—ST-segment elevation myocardial infarction; UA =
unstable angina; UFH = unfractionated heparin.
a
 For full dosing information, see Table 13 in reference 42.
b
 For example, recurrent symptoms/ischemia, heart failure, or serious arrhythmia.
c
 For more details on management of patients with UA/NSTEMI after diagnostic
angiography, see Figure 9 of reference 42.
d
 See recommendations in section 3.2.3 of reference 42.
From J Am Coll Cardiol,42 with permission from Elsevier.

Antiplatelet Therapy
Aspirin. Aspirin blocks the synthesis of thromboxane A2 by irreversibly inhibiting
cyclooxygenase 1, thereby diminishing platelet aggregation. Four randomized trials have
each demonstrated that, compared with placebo, aspirin reduces the risk of death or MI by
more than 50% for patients presenting with UA/NSTEMI.35,36,119,120 The ACC/AHA guidelines
recommend an initial daily dose of 162 to 325 mg, followed by a daily dose of 75 to 162 mg
for long-term secondary prevention.42 Absolute contraindications to aspirin therapy include
documented aspirin allergy (eg, asthma or anaphylaxis), active bleeding, or a known platelet
disorder. Clopidogrel is a recommended alternative for patients who cannot tolerate aspirin.42
Clopidogrel. Clopidogrel is a thienopyridine derivative that blocks the P2Y12 adenosine
diphosphate (ADP) receptor on platelets. This action decreases platelet activation and
aggregation, increases bleeding time, and reduces blood viscosity. Therapy with clopidogrel
and aspirin is recommended for essentially all patients with UA/NSTEMI.
The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial randomly
assigned 12,562 patients to receive either aspirin alone (75-325 mg/d) or aspirin plus
clopidogrel (300-mg loading dose, then 75 mg/d).121 The incidence of the primary end point
of cardiovascular death, MI, or stroke was 20% lower for both low-risk and high-risk patients
with UA/NSTEMI who received aspirin plus clopidogrel (11.4%) than for those who
received aspirin alone (9.3%; P<.0001).38 Benefit was seen as early as 24 hours after the
initiation of treatment (the Kaplan-Meier curves began diverging after just 2 hours) and
continued throughout the trial's 1-year treatment period. Clopidogrel was associated with
substantially more instances of major bleeding but not with more instances of life-threatening
bleeding. The prespecified subgroup analysis, PCI-CURE, found that treatment with
clopidogrel before PCI was also associated with a substantial benefit: the reduction in cardiac
events was 31% at 30 days and at 1 year.122
On the basis of the results of the PCI-CURE trial, the CREDO (Clopidogrel for the Reduction
of Events During Observation) trial and the CLARITY-TIMI 28 (Clopidogrel as Adjunctive
Reperfusion Therapy—Thrombolysis in Myocardial Infarction 28) trial, together with the
results of a meta-analysis (which found that, in comparison with no pretreatment, clopidogrel
pretreatment reduced the incidence of cardiovascular death, MI, or stroke from randomization
through 30 days by 41%; P=.001123), the 2005 guidelines from the ACC, the AHA, and the
Society for Coronary Angiography and Interventions contain a class I, level of evidence A
recommendation for clopidogrel pretreatment before PCI.124,125
The risk of major bleeding was increased when patients had received clopidogrel within 5
days before undergoing CABG.38 Therefore, the ACC/AHA guidelines recommend
discontinuing the administration of clopidogrel at least 5 days before surgery, if
possible.42,126 The current practice in most hospitals is either to initiate clopidogrel
administration at the time of admission (this action affords the benefits of reducing the
incidence of early ischemic events and of pretreatment before PCI) or to delay treatment until
after coronary angiography has been performed, in which case the drug can be either
administered while PCI is carried out or withheld until after CABG has been performed.
Newer P2Y12 ADP Inhibitors. A high rate of recurrent atherothrombotic events despite the
administration of dual-antiplatelet therapy with aspirin and clopidogrel has sparked great
interest in finding more potent inhibitors of the P2Y12 ADP receptor.
Prasugrel is an irreversible P2Y12 ADP receptor antagonist that was recently approved by the
US Food and Drug Administration. Several studies have shown that prasugrel achieves much
higher (nearly double) levels of platelet inhibition than does daily clopidogrel dosing of 75
mg or even 150 mg.127 The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic
Outcomes by Optimizing Platelet Inhibition With Prasugrel—Thrombolysis in Myocardial
Infarction 38) trial administered prasugrel (a 60-mg loading dose and a 10-mg daily
maintenance dose) or clopidogrel to 13,608 high-risk patients with ACS who were scheduled
for PCI.128 The incidence of the primary end point of cardiovascular death, MI, or stroke at 6
to 15 months was significantly lower in the prasugrel group (9.9%) than in the clopidogrel
group (12.1%; P<.001). The incidence of stent thrombosis was 52% lower with prasugrel
(1.1%) than with clopidogrel (2.4%; P<.001). The risk of TIMI major bleeding, including the
risk of fatal bleeding, was higher for the patients receiving prasugrel (2.4%) than for those
receiving clopidogrel (1.8%; P=.03).
Ticagrelor (AZD6140) is a reversible oral P2Y12 receptor antagonist with a half-life of
approximately 12 hours. The recently completed PLATO (Study of Platelet Inhibition and
Patient Outcomes) randomized 18,624 patients with ACS to either ticagrelor (loading dose of
180 mg followed by 90 mg twice daily) or clopidogrel for up to 12 months.129 The primary
end point of death from vascular causes, MI, or stroke occurred in 9.8% of patients receiving
ticagrelor vs 11.7% of those receiving clopidogrel (HR, 0.84; 95% CI, 0.77-0.92; P<.001).
The rate of death from any cause was also reduced with ticagrelor vs clopidogrel (4.5% vs
5.9%; P<.001). The rates of major bleeding overall were similar between the ticagrelor and
clopidogrel groups (11.6% vs 11.2%; P=.43).
GP IIb/IIIa Inhibitors. The platelet GP IIb/IIIa inhibitors are potent and specific inhibitors
of platelet aggregation. They act by interrupting the final common pathway of fibrinogen-
mediated cross-linkage of platelets. Several large trials involving patients with UA/NSTEMI
have shown that the GP IIb/IIIa inhibitors are of substantial benefit for patients at high risk,
those undergoing PCI, or both.39,130 Three agents are currently available for use: abciximab,
eptifibatide, and tirofiban. Abciximab is indicated only if angiography will not be appreciably
delayed and PCI is likely to be performed; otherwise, IV eptifibatide or tirofiban is the
preferred choice. The main risk associated with GP IIb/IIIa inhibitors is an increased rate of
hemorrhage, usually at the site of vascular intervention. Therefore, patients should be
monitored closely for bleeding, and complete blood cell counts should be determined
regularly.
The benefit of GP IIb/IIIa inhibition appears to be greatest for patients at higher risk of
complications, eg, those with elevated troponin concentrations,62,63 diabetes,66 ST-segment
changes,39 recurrent angina,39,131 previous aspirin use,132 or a TIMI risk score of 4 or
higher.83 The benefit of GP IIb/IIIa inhibition has been confirmed even for patients who have
been pretreated with clopidogrel.133 The optimal timing for the initiation of GP IIb/IIIa
inhibitors has been debated. The EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in
Non-ST-Segment Elevation Acute Coronary Syndrome) trial involved 9492 patients who
were randomly assigned either to early GP IIb/IIIa inhibition or to the provisional use of GP
IIb/IIIa inhibitors after angiography. The results showed that early eptifibatide exerted no
statistically significant benefit in reducing the composite end point of adverse cardiovascular
events but was associated with a statistically significant increase in bleeding rates.134
The 2007 ACC/AHA guidelines recommend that, for patients with UA/NSTEMI who will be
treated initially according to an invasive strategy, either an intravenous GP IIb/IIIa inhibitor
or clopidogrel should be added to aspirin and anticoagulant therapy (upstream) before
diagnostic angiography is performed (class I recommendation). They also state that adding
both agents is reasonable (class IIa recommendation).42

Anticoagulant Therapy
The 2007 ACC/AHA UA/NSTEMI guidelines recommend the initiation of anticoagulant
therapy for all patients (without contraindications) as soon as possible after presentation
(class I recommendation). The guidelines recommend 4 agents as options: unfractionated
heparin (UFH), enoxaparin, fondaparinux, and bivalirudin (approved only for patients
managed according to an invasive strategy).
Unfractionated Heparin. The results of several randomized trials suggest that UFH is
associated with lower rates of death or MI than is aspirin alone.36,120,135 The anticoagulant
effects of UFH are variable.136 The ACC/AHA guidelines recommend weight-adjusted dosing
of UFH (60 U/kg bolus and 12 U/kg/hr infusion), frequent monitoring of activated partial
thromboplastin time (every 6 hours until 2 consecutive values are within the target range, and
every 24 hours thereafter), and titration of UFH according to a standardized nomogram with a
target range of activated partial thromboplastin time between 1.5 and 2.0 times that of
control, or approximately 50 to 70 seconds.42 Administration of UFH should continue for at
least 48 hours after presentation with UA/NSTEMI.42
Complete blood cell counts should be determined at least daily during therapy with UFH.
Autoimmune heparin-induced thrombocytopenia in association with thrombosis is a rare but
dangerous complication of UFH administration (incidence is <0.2%).137 When clinical
findings suggest that this complication has occurred, all heparin therapy should be
immediately discontinued.
Low—Molecular-Weight Heparin. Because the rates of recurrence of ischemic events
remain high even when UFH is administered, low—molecular-weight heparins (LMWHs)
were developed with the goal of providing improved anticoagulation. They are active against
both factor Xa and factor IIa; therefore, they inhibit both the action and the generation of
thrombin. Their other advantages over UFH include a lower rate of
thrombocytopenia,138 more bioavailability, and less binding to plasma proteins, a factor that
renders monitoring the level of anticoagulation unnecessary.
Various LMWHs (dalteparin, enoxaparin, and nadroparin) have been compared with UFH for
the treatment of UA/NSTEMI, but only enoxaparin has been found to have a clear benefit.
Early trials, such as ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-
Wave Coronary Events) and the TIMI 11B, showed that, compared with UFH, enoxaparin
achieved a 20% reduction in the incidence of death, MI, recurrent ischemia, or some
combination of these factors.139 The SYNERGY (Superior Yield of the New Strategy of
Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors) trial found that
enoxaparin was not inferior to UFH in the setting of an early invasive strategy.140 However,
enoxaparin achieved a clear benefit over UFH in the setting of a conservative strategy, as
shown by the older trials and the more recent A-to-Z (Aggrastat to Zocor) trial.141 The 2007
ACC/AHA guidelines contain a class IIa recommendation stating that enoxaparin or
fondaparinux (see Factor Xa Inhibitors) is preferable to UFH as anticoagulant therapy for
UA/NSTEMI patients who will be treated conservatively, unless CABG is planned within 24
hours.42 The benefit of enoxaparin is greater for patients at higher risk, such as those with ST-
segment deviation,142 elevated troponin concentrations,143 and high TIMI risk scores.82 The
rates of major bleeding associated with LMWHs have been found to be similar to those
associated with UFH, with 1 exception: the SYNERGY trial found a statistically significant
increase in the incidence of major bleeding in association with enoxaparin administration.140
Direct Thrombin Inhibitors. Direct thrombin inhibitors have several potential advantages
over indirect thrombin inhibitors (such as UFH or LMWH): they do not require a cofactor
such as antithrombin for their action and can thus directly inhibit clot-bound thrombin; they
do not interact with plasma proteins; and they do not cause thrombocytopenia.
The administration of bivalirudin to patients with UA/NSTEMI was recently studied in the
ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, which
randomly assigned 13,819 patients with ACS managed with an early invasive strategy to one
of 3 antithrombotic regimens: UFH (or enoxaparin) plus a GP IIb/IIIa inhibitor, bivalirudin
plus a GP IIb/IIIa inhibitor, or bivalirudin alone.144 No differences in the rates of the primary
end point (composite of death, MI, unplanned revascularization for ischemia, and major
bleeding at 30 days) were observed between the group receiving UFH plus a GP IIb/IIIa
inhibitor and the group receiving bivalirudin plus a GP IIb/IIIa inhibitor. However, the 30-
day net clinical outcomes were significantly better for the group receiving bivalirudin alone
than for the group receiving UFH plus a GP IIb/IIIa inhibitor (rates of primary end point,
10.1% vs 11.7%; P=.015); this difference was due primarily to a substantially reduced rate of
major bleeding. The ACC/AHA guidelines have given bivalirudin a class I recommendation
for the treatment of patients with UA/NSTEMI selected for an early invasive strategy. The
guidelines further state that it is reasonable to omit the administration of an intravenous GP
IIb/IIIa antagonist if a thienopyridine is administered simultaneously with bivalirudin (class
IIa recommendation).42
The 2007 ACC/AHA guidelines recommend the use of other direct thrombin inhibitors, such
as lepirudin (recombinant hirudin) and argatroban, only for patients with heparin-induced
thrombocytopenia.42
Factor Xa Inhibitors. Fondaparinux is a synthetic pentasaccharide that is an indirect factor
Xa inhibitor and requires antithrombin for its action. The OASIS-5 (Fifth Organization to
Assess Strategies in Acute Ischemic Syndromes) trial, which involved 20,078 patients with
high-risk UA/NSTEMI, compared subcutaneous fondaparinux at a once-daily dose of 2.5 mg
with standard-dose enoxaparin.145 Fondaparinux was found to be not inferior to enoxaparin in
reducing the incidence of the primary outcomes of death, MI, or refractory ischemia at 9
days. The rate of major bleeding, however, was almost 50% lower in the fondaparinux arm
than in the enoxaparin arm, and analyses using the composite variable of the primary
outcome and major bleeding at 9 days demonstrated an advantage of fondaparinux over
enoxaparin (incidence, 7.3% vs 9.0%; HR, 0.81; P<.001). Fondaparinux was also associated
with a statistically significant reduction in 30-day and 6-month mortality rates. In the subset
of patients undergoing PCI, the risk of catheter-related thrombi was more than 3 times higher
in the fondaparinux arm than in the enoxaparin arm; supplemental UFH at the time of
catheterization appeared to minimize the risk of this complication.
The 2007 ACC/AHA guidelines contain a class I recommendation for fondaparinux as
treatment for patients with UA/NSTEMI who will be managed by either a conservative
strategy or an early invasive strategy, unless CABG is planned within 24 hours.42 They
further state that fondaparinux is preferred over other anticoagulants for patients who are
selected for a conservative treatment strategy and who are at an increased risk of bleeding
(class I recommendation).
Oral Anticoagulation. Trials of oral anticoagulation with warfarin after ACS have
demonstrated the benefit of the combination of warfarin plus aspirin over aspirin alone,
provided a sufficient degree of anticoagulation was achieved.146-148 However, a similar degree
of benefit is seen with clopidogrel plus aspirin rather than with aspirin alone, without the
drawback of monitoring the international normalized ratio, as is necessary with warfarin
therapy. In addition, the use of clopidogrel is well established for patients with ACS who
undergo PCI and stenting. Thus, the clinical use of aspirin plus warfarin is limited.
Occasionally, an indication for warfarin, in addition to aspirin and clopidogrel, arises after
UA/NSTEMI (eg, for patients with atrial fibrillation, a mechanical prosthetic valve, or LV
thrombus).
Discharge Antithrombotic Therapy. The 2007 ACC/AHA guidelines provide clear
recommendations for antithrombotic therapy at the time of discharge; these recommendations
are based on the management strategy (Figure 5). The benefits and risks of triple
antithrombotic therapy with aspirin, clopidogrel, and warfarin have not been clearly
established. Such therapy should be selected only when clear indications are present and
should be administered for the shortest possible time and at the lowest effective doses:
aspirin, 81 mg; warfarin, titrated to the dosage necessary to sustain an international
normalized ratio of 2.0 to 2.5 (class IIb recommendation).42

FIGURE 5.

Long-term antithrombotic therapy at hospital discharge after unstable angina (UA)/non—ST-

segment elevation myocardial infarction (NSTEMI). LOE = level of evidence.
a
 For patients allergic to aspirin, use clopidogrel alone indefinitely, or try aspirin
desensitization.
b
 For patients allergic to clopidogrel, use ticlopidine, 250 mg by mouth twice daily.
c
 Continue aspirin indefinitely and warfarin longer term as indicated for such specific
conditions as atrial fibrillation; left ventricular thrombus; and cerebral, venous, or pulmonary
emboli.
d
 When warfarin is added to aspirin plus clopidogrel, an international normalized ratio of 2.0
to 2.5 is recommended.
From J Am Coll Cardiol,42 with permission from Elsevier.

LIPID-LOWERING THERAPY
In the absence of contraindications, lipid-lowering therapy with statins should be initiated for
all patients with UA/NSTEMI, regardless of baseline LDL cholesterol levels. If the LDL
cholesterol concentration is 100 mg/dL (to convert to mmol/L, multiply by 0.0259) or higher,
cholesterol-lowering therapy should be initiated or intensified with the goal of achieving an
LDL cholesterol concentration lower than 100 mg/dL. An update to both the Adult Treatment
Panel III guidelines149 and the 2007 ACC/AHA guidelines42 states that further titration to a
dose necessary to sustain an LDL cholesterol concentration of 70 mg/dL or lower is
reasonable (class IIa recommendation).
The LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial
demonstrated that, compared with placebo, pravastatin achieved a 26% reduction in mortality
rates (P=.004) for patients with UA, as well as statistically significant reductions in the
incidence of subsequent MI, coronary revascularization, and stroke.150 The PROVE IT
(Pravastatin or Atorvastatin Evaluation and Infection Therapy)-TIMI 22 trial found that,
compared with moderate lipid lowering after ACS with standard-dose pravastatin (40 mg/d),
intensive lipid lowering with high-dose atorvastatin (80 mg/d) achieved a 16% reduction in
the primary composite end point of all-cause death, MI, UA requiring rehospitalization or
revascularization, and stroke.151 The benefit was linked to statistically significant reductions
in both LDL cholesterol and CRP concentrations.
Sumber : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755812/

7. Perform ECG examination

Cara Menggunakan EKG untuk merekam listrik jantung :

Persiapan

A. Alat

 Mesin EKG, yang dilengkapi :

 kabel untuk sumber listrik
 kabel untuk bumi (ground)
 Kabel elektroda ekstremitas dan dada
 Plat elektroda ekstremitas beserta karet pengikat
 Balon penghisap elektroda dada
 Jelly
 Kertas tissue
 Kapas Alkohol
 Kertas EKG
 Spidol
B. Pasien

Penjelasan (informed consent)

- Tujuan pemeriksaan

- Hal-hal yang perlu diperhatikan saat perekaman

Dinding dada harus terbuka dan tidak ada perhiasan logam yang melekat.

Pasien diminta tenang atau tidak bergerak saat perekaman EKG

Cara memasang EKG

1. Pasang semua komponen/kabel-kabel pada mesin EKG

2. Nyalakan mesin EKG

3. Baringkan pasien dengan tenang di tempat tidur yang luas. Tangan dan kaki tidak saling
bersentuhan

4. Bersihkan dada, kedua pergelangan kaki dan tangan dengan kapas alcohol (kalau perlu
dada dan pergelangan kaki dicukur)

5. Keempat electrode ektremitas diberi jelly.

6. Pasang keempat elektrode ektremitas tersebut pada kedua pergelangan tangan dan kaki.
Untuk tangan kanan biasanya berwarna merah, tangan kiri berwarna kuning, kaki kiri
berwarna hijau dan kaki kanan berwarna hitam.

7. Dada diberi jelly sesuai dengan lokasi elektrode V1 s/d V6.

- V1 di garis parasternal kanan sejajar dengan ICS 4 berwarna merah

- V2 di garis parasternal kiri sejajar dengan ICS 4 berwarna kuning

-V3 di antara V2 dan V4, berwarna hijau

- V4 di garis mid klavikula kiri sejajar ICS 5, berwarna coklat

- V5 di garis aksila anterior kiri sejajar ICS 5, berwarna hitam

- V6 di garis mid aksila kiri sejajar ICS 5, berwarna ungu

1. Pasang elektrode dada dengan menekan karet penghisap.

2. Buat kalibrasi

3. Rekam setiap lead 3-4 beat (gelombang), kalau perlu lead II panjang (minimal 6 beat)

4. Kalau perlu buat kalibrasi setelah selesai perekaman

5. Semua electrode dilepas

6. Jelly dibersihkan dari tubuh pasien

7. Beritahu pasien bahwa perekaman sudah selesai

8. Matikan mesin EKG

9. Tulis pada hasil perekaman : nama, umur, jenis kelamin, jam, tanggal, bulan dan tahun
pembuatan, nama masing-masing lead serta nama orang yang merekam

10.Bersihkan dan rapikan alat

Perhatian :

 Sebelum bekerja periksa kecepatan mesin 25 mm/detik dan voltase 10 mm. Jika
kertas tidak cukup kaliberasi voltase diperkecil menjadi ½ kali atau 5 mm. Jika
gambaran EKG kecil, kaliberasi voltase diperbesar menjadi 2 kali atau 20 mm.
 Hindari gangguan listrik dan mekanik saat perekaman
 Saat merekam, operator harus menghadap pasien
Sumber : https://www.ncbi.nlm.nih.gov/books/NBK549803/

8. Interpret ECG results on ACS

ECG Findings for the Diagnosis of Acute Coronary Syndrome

NEGATIV
POSITIVE E
PREDICTI PREDICTI
ECG LESIO SENSITI SPECIFI VE VALUE VE VALUE
FINDINGS N VITY (%) CITY (%) (%) (%)

ST-segment Right 90 71 94 70
elevation greater coronary
in lead III than in artery
lead II plus ST-
segment
depression of > 1
mm in lead I, lead
aVL, or both

Absence of the Left 83 96 91 93

above circumfle
findings plus ST- x
segment elevation coronary
in leads I, aVL, artery
V5, and V6 and
ST-segment
depression in leads
V1, V2, and V3

ST-segment elevation in leads V1, V2, and V3 plus any of the features below:

ST-segment Proximal 12 100 100 61

elevation of > LAD
2.5 mm in lead coronary
 NEGATIV
POSITIVE E
PREDICTI PREDICTI
ECG LESIO SENSITI SPECIFI VE VALUE VE VALUE
FINDINGS N VITY (%) CITY (%) (%) (%)

V1, right artery

bundle branch
block with Q
wave, or both

ST-segment Proximal 34 98 93 68
depression of > LAD
1 mm in leads coronary
II, III, and aVF artery

ST-segment Distal 66 73 78 62
depression of ≤ LAD
1 mm or ST- coronary
segment artery
elevation in
leads II, III,
and aVF

In acute coronary syndrome, common electrocardiographic abnormalities include T-wave

tenting or inversion, ST-segment elevation or depression (including J-point elevation in
multiple leads), and pathologic Q waves.

Sumber : https://www.aafp.org/afp/2005/0701/p119.html