Mi

ACS/Myocardial
Infarction
Dr. Prasad B. Chinchole
Doctor of Pharmacy
SCOP, Almala
©Dr.Prasad Chinchole

Index
1. Introduction
2. Terminology
3. Definition
4. Epidemiology
5. Etiology
6. Risk factors
7. Pathogenesis
8. Complications
9. Signs and Symptoms
10.Diagnosis
11.Management (Treatment Goals)
12. Non-pharmacological Treatment
13.Pharmacological Treatment
14.Evaluation of Therapeutic Management
15.Conclusion
©Dr.Prasad Chinchole

Introduction
▪ Acute coronary syndromes (ACSs), including unstable angina and
myocardial infarction (MI), are forms of coronary heart disease (CHD)
that constitute the most common cause of CVD death.
▪ The cause of an ACS is erosion or rupture of an atherosclerotic plaque
with subsequent platelet adherence, activation, aggregation, and
activation of the clotting cascade. Ultimately, a clot composed of fibrin
and platelets forms.
▪ Myocardial infarction (MI), commonly known as a heart attack,
occurs when blood flow decreases or stops to a part of the heart, causing
damage to the heart muscle.
▪ The most common symptom is chest pain or discomfort which may travel
into the shoulder, arm, back, neck, or jaw.
@Dr.Prasad Chinchole

▪ Often it is in the center or left side of the chest and lasts for more than
a few minutes.
▪ The discomfort may occasionally feel like heartburn.
▪ Other symptoms may include shortness of breath, nausea, feeling faint,
a cold sweat, or feeling tired.
▪ About 30% of people have atypical symptoms.
▪ Women more often have atypical symptoms than men.
▪ Among those over 75 years old, about 5% have had an MI with little or
no history of symptoms. An MI may cause heart failure, an irregular
heartbeat, cardiogenic shock, or cardiac arrest.

Terminology
▪ Myocardial infarction (MI) refers to tissue death (infarction) of the
heart muscle (myocardium)
▪ It is a type of acute coronary syndrome, which describes a sudden or
short-term change in symptoms related to blood flow to the heart.
▪ The phrase "heart attack" is often used non-specifically to refer to a
myocardial infarction and to sudden cardiac death.
▪ An MI is different from—but can cause—cardiac arrest, where the
heart is not contracting at all or so poorly that all vital organs cease to
function.
▪ It is also distinct from heart failure, in which the pumping action of the
heart is impaired. However, an MI may lead to heart failure

Definition
▪ The term "myocardial infarction" focuses on the myocardium (the heart
muscle) and the changes that occur in it due to the sudden deprivation
of circulating blood.
▪ The main change is necrosis (death) of myocardial tissue.
▪ The word "infarction" comes from the Latin "infarcire" meaning "to
plug up or cram."
▪ It refers to the clogging of the artery.

Epidemiology
▪ Myocardial infarction is a common presentation of coronary artery
disease. The World Health Organization estimated in 2004, that 12.2%
of worldwide deaths were from ischemic heart disease.
▪ Worldwide, more than 3 million people have STEMIs and 4 million
have NSTEMIs a year.
▪ STEMIs occur about twice as often in men as women.
▪ In contrast, IHD is becoming a more common cause of death in the
developing world.
▪ For example, in India, IHD had become the leading cause of death by
2004, accounting for 1.46 million deaths (14% of total deaths) and
deaths due to IHD were expected to double during 1985–2015.

Etiology & Risk factors
1. Atherosclerotic plaques
2. Inflammation
3. Genetic
4. Decrease synthesis of nitric oxide
5. Evolution of endothelial
dysfunction
6. Atherosclerosis
7. including hypertension
8. Age
9. Male gender
10. Tobacco use
11. Diabetes Mellitus
12. Obesity
13. Dyslipidemias
14. Lack of physical activity
15. Illegal drug use
16. A history of preeclampsia

Pathogenesis

SPECTRUM OF ACS
▪ Acute coronary syndromes (ACSs) is a term that includes all
clinical syndromes compatible with acute myocardial ischemia
resulting from an imbalance between myocardial oxygen demand
and supply.
▪ In contrast to stable angina, an ACS results primarily from
diminished myocardial blood flow secondary to an occlusive or
partially occlusive coronary artery thrombus.
▪ ACSs are classified according to electrocardiographic (ECG)
changes into STE ACS, also called STEMI, and NSTE ACS, which
includes NSTE MI and unstable angina

PLAQUE RUPTURE AND CLOT FORMATION

VENTRICULAR REMODELING FOLLOWING
AN ACUTE MI

COMPLICATIONS
▪ it is important for clinicians to recognize complications of MI because
they are associated with increased mortality.
▪ The most serious complication is cardiogenic shock, which occurs in
approximately 5% to 6% of patients presenting with STEMI and in less
than 2% of those presenting with NSTE ACS.
▪ Other complications that may result from MI are heart failure, valvular
dysfunction, ventricular and atrial tachyarrhythmias, bradycardia, heart
block, pericarditis, stroke secondary to LV thrombus embolization,
venous thromboembolism, and LV free-wall rupture.
▪ More than 25% of MI patients die, presumably of ventricular
fibrillation, prior to reaching the hospital.

Signs and Symptoms
CLINICAL PRESENTATION
Symptoms
▪ The classic symptom of ACS is
midline anterior chest discomfort.
Accompanying symptoms may
include arm, back or jaw pain,
nausea, vomiting, or shortness of
breath.
▪ Patients less likely to present with
classic symptoms include elderly
patients, diabetic patients, and
women.
Signs
▪ No signs are classic for ACS.
▪ However, patients with ACS may
present with signs of acute heart
failure, including jugular venous
distension, rales, and S3 sound on
auscultation.
▪ Patients may present with
arrhythmias and therefore may
have tachycardia, bradycardia, or
heart block.

Diagnosis
1. SYMPTOMS AND PHYSICAL EXAMINATION FINDINGS
▪ The classic symptom of an ACS is midline anterior anginal chest
discomfort, most often at rest, severe new-onset angina, or increasing
angina at least 20 minutes in duration.
▪ The chest discomfort may radiate to the shoulder, down the left arm,
to the back, or to the jaw.
▪ Associated symptoms that may accompany chest discomfort include
nausea, vomiting, diaphoresis, and shortness of breath.

▪ Typically, patients with STE ACS present with unremitting chest
discomfort.
▪ Patients with NSTE ACS may present with (1) rest angina, (2) new
onset (<2 months) angina, or (3) angina that increases in frequency,
duration, or intensity. All healthcare professionals should review these
warning symptoms with patients at high risk for CHD.
▪ On physical examination, no specific features are indicative of ACS.

2. TWELVE-LEAD ECG
▪ Key features of a 12-lead ECG identify and risk stratify patients with an
ACS.
▪ Within 10 minutes of a patient presenting to an emergency department with
symptoms of ischemic chest discomfort, a 12-lead ECG should be obtained
and interpreted.
▪ Key findings on review of a 12-lead ECG indicating myocardial ischemia
or MI are ST-segment elevation, ST-segment depression, and T-wave
inversion.
▪ ST-segment and/or T-wave changes in contiguous leads help to identify the
location of the coronary artery that is the cause of the ischemia or
infarction.

▪ In addition, the appearance of a new left bundle-branch block
accompanied by chest discomfort is highly specific for acute MI.
▪ Approximately 65% of patients diagnosed with MI present with STE
on ECG; the remainder have ST-segment depression, T-wave inversion,
or in some instances, no ECG changes.
▪ Some parts of the heart are more “electrically silent” than others, and
myocardial ischemia may not be detected on surface ECG.
▪ Therefore, it is important to review findings from the ECG in
conjunction with biochemical markers of myocardial necrosis.

3. BIOCHEMICAL MARKERS
▪ Biochemical markers of myocardial cell death are important for confirming
the diagnosis of MI.
▪ These are termed positive biochemical markers for MI.
▪ Although troponins and CK MB appear in the blood within 6 hours of
infarction, troponins stay elevated in the blood for up to 10 days, whereas
CK MB returns to normal values within 48 hours.
▪ Therefore, if a patient is admitted with elevated troponin and CK MB
concentrations and several days later experiences recurrent chest discomfort,
the troponin will be less sensitive for detecting new myocardial damage
because the level still is elevated from the earlier event.

▪ If early re-infarction is suspected, CK MB concentration determination
is the preferred diagnostic test.
▪ Biochemical markers, such as troponin measurements, that are below
the detectable limit of hospital laboratories are termed negative, and the
diagnosis of MI is excluded.
▪ CK MB normal Value 5 to 25 IU/L.
▪ Troponin normal Value less than 0.01 ng/mL.

RISK STRATIFICATION
▪ Patient signs and symptoms, medical history, ECG, and troponin or CK MB
determinations are used to stratify patients as having low, medium, or high
risk of death or MI or likelihood of not responding to pharmacotherapy and
requiring urgent coronary angiography and Percutaneous coronary
intervention PCI.
▪ The ACC/AHA defines a target time to initiate reperfusion treatment for
STEMI within 30 minutes of hospital presentation for fibrinolytics and within
no more than 90 minutes from resentation for primary PCI.
▪ Approximately 83% of eligible patients presenting to the hospital with
STEMI underwent reperfusion therapy; 62% of the patients were treated with
primary PCI, 17% fibrinolysis alone, 1% fibrinolysis followed by immediate
PCI, and 2% immediate CABG surgery.

Management
A. DESIRED OUTCOMES
▪ The short-term goals of treatment for the ACS patient are as follows:
1. Early restoration of blood flow to the infarct-related artery to prevent
infarct expansion (in the case of MI) or prevent complete occlusion and
MI (in unstable angina)
2. Prevention of death and other complications
3. Prevention of coronary artery reocclusion
4. Relief of ischemic chest discomfort
5. Maintenance of normoglycemia

GENERAL APPROACH TO TREATMENT
▪ General treatment measures for all STE ACSs and high- and
intermediate-risk NSTE ACS patients include admission to hospital,
oxygen administration (if oxygen saturation is low, i.e., <90%).
▪ Continuous multilead ST-segment monitoring for arrhythmias and
ischemia, glycemic control, frequent measurement of vital signs,
bedrest for 12 hours in hemodynamically stable patients, avoidance of
Valsalva maneuver (prescribe stool softeners routinely), and pain relief.
▪ If these test results are negative, the patient may be admitted to a
general medical floor with ECG telemetry monitoring for ischemic
changes and arrhythmias, undergo a noninvasive stress test, or be
discharged from the emergency department.

NONPHARMACOLOGIC THERAPY
▪ Either fibrinolysis or immediate primary PCI is the treatment of choice
for reestablishing coronary artery blood flow in patients with STE ACS
when the patient presents within 3 hours of symptom onset and both
options are available at the institution.
▪ For primary PCI, the patient is taken from the emergency department
to the cardiac catheterization laboratory and undergoes coronary
angiography with either balloon angioplasty or placement of a bare-
metal or drug-eluting intracoronary stent.
▪ Compliance—give careful advice about disease, treatment, and self
help strategies
▪ Diet—ensure adequate general nutrition and, in obese patients, weight
reduction

▪ Salt—advise patients to avoid high salt content foods and not to add salt
(particularly in severe cases of congestive heart failure)
▪ Fluid—urge overloaded patients and those with severe congestive heart
failure to restrict their fluid intake
▪ Alcohol—advise moderate alcohol consumption (abstinence in alcohol
related cardiomyopathy)
▪ Smoking—avoid smoking (adverse effects on coronary disease, adverse
haemodynamic effects)
▪ Exercise—regular exercise should be encouraged
▪ Vaccination—patients should consider influenza and pneumococcal
vaccinations
▪ Contraceptive advice

Commonly consumed processed foods that have a
high sodium content
▪ Cheese
▪ Sausages
▪ Crisps, salted peanuts
▪ Milk and white chocolate
▪ Tinned soup and tinned vegetables
▪ Ham, bacon, tinned meat (eg. corned beef)
▪ Tinned fish (eg. sardines, salmon, tuna)
▪ Smoked fish

EARLY PHARMACOTHERAPY FOR STE ACS

▪ According to the ACC/AHA STE ACS practice guidelines, early
pharmacotherapy of STE ACS should include intranasal oxygen (if
oxygen saturation is <90%), sublingual (SL) nitroglycerin (NTG),
aspirin, a β-blocker, unfractionated heparin (UFH) or enoxaparin, and
fibrinolysis in eligible candidates.
▪ Morphine is administered to patients with refractory angina as an
analgesic and a venodilator that lowers preload.
▪ These agents should be administered early, while the patient is still in
the emergency department. An ACE inhibitor should be started within
24 hours of presentation, particularly in patients with LVEF ≤40%,
signs of heart failure, or an anterior wall MI, in the absence of
contraindications.

▪ Intravenous (IV) NTG and β-blockers should be administered to
selected patients without contraindications.
▪ Dosing and contraindications for SL and IV NTG, aspirin, β-blockers,
UFH, enoxaparin, ACE inhibitors, and fibrinolytics are

Fibrinolytic Therapy
▪ Fibrinolytic drug, also called thrombolytic drug, any agent that is
capable of stimulating the dissolution of a blood clot (thrombus).
▪ Fibrinolytic drugs work by activating the so-called fibrinolytic
pathway.
▪ This distinguishes them from the anticoagulant drugs (coumarin
derivatives and heparin), which prevent the formation of blood clots by
suppressing the synthesis or function of various clotting factors that are
normally present in the blood.
▪ Administration of a fibrinolytic agent is indicated in patients with STE
ACS who present to the hospital within 12 hours of onset of chest
discomfort and have at least 1 mm of STE in two or more contiguous
ECG leads or a new left bundle-branch block.

▪ Fibrinolytic therapy also should be considered in patients presenting
within 12–24 hours of onset of chest discomfort and have persistent
symptoms of ischemia and at least 1 mm of STE in two or more
contiguous leads.
▪ Because administration of fibrinolytics results in clot lysis, patients at
high risk for major bleeding, including those with ICH, have either
relative or absolute contraindications.
▪ Patients presenting with an absolute contraindication likely will not
receive fibrinolytic therapy, and primary PCI is preferred.
▪ Fibrinolytic therapy is controversial in patients older than 75 years.
▪ Stroke rates also grow in number with increasing patient age.

Adverse Drug Reactions
▪ Non-cardiogenic pulmonary edema.
▪ Hypotension.
▪ Fever and shivering.
▪ History of cerebrovascular hemorrhage at any time.
▪ Nonhemorrhagic stroke or other cerebrovascular event within the past year.
▪ Marked hypertension ( reliably determined systolic arterial pressure >180
mmHg and/or a diastolic pressure >110 mmHg) at any time during
presentation.
▪ Suspicion of aortic dissection.
▪ Active internal bleeding (excluding menses).

Relative contraindications to thrombolytic therapy
▪ Current use of anticoagulats (INR 2).
▪ A recent (<2 weeks) invasive or surgical procedure or prolonged (10
min) cardiopulmonaty resuscitation .
▪ Known bleeding diathesis.
▪ Pregnancy.
▪ Hemorrhagic ophthalmic condition.
▪ Active peptic ulcer disease.
▪ History of severe hypertension that is currently adequately controlled

Aspirin
▪ Based on several randomized trials, aspirin has become the preferred
antiplatelet agent for treatment of all ACSs.
▪ Early aspirin administration to all patients without contraindications
within the first 24 hours of hospital admission is a quality care
indicator.
▪ The antiplatelet effects of aspirin are mediated by inhibition of
thromboxane A2 synthesis through irreversible inhibition of platelet
cyclooxygenase- 1 (COX-1).
▪ Following administration of a non–enteric-coated formulation, aspirin
rapidly (<10 minutes) inhibits thromboxane A2 production in the
platelets.

▪ Aspirin also has anti-inflammatory actions, which decrease C-reactive
protein and may contribute to its effectiveness in ACS.
▪ In patients experiencing an ACS, an initial dose equal to greater than
160 mg nonenteric aspirin is necessary to achieve rapid platelet
inhibition.
▪ This first dose can be chewed in order to achieve high blood
concentrations and rapid platelet inhibition.
▪ Current data suggest that although an initial dose of 160 to 325 mg is
required, long-term therapy with doses of 75 to 150 mg daily are as
effective as higher doses and, therefore,48 a daily maintenance dose of
75 to 160 mg is recommended in most patients to inhibit the 10% of
the total platelet pool that is regenerated daily.

MOA ADR
▪ Abdominal or Stomach Pain, Cramping, or
Burning, Black, Tarry Stools, Bloody or Cloudy
Urine.
▪ Change In Consciousness, Chest Pain or
Discomfort, Confusion, Constipation.
▪ Decreased Frequency or Amount of Urine,
Diarrhea.
▪ Difficult Breathing, Drowsiness, Fainting, Fast
Breathing.

Dose
Indication Administrati
on
Initial loading dose Maintenance dose
Dose Interval Dose Interval
Headache oral 500 mg 4 to 6 hours - -
Platelet
inhibition*
oral 100 mg 24 hours 100 mg 24 hours

Thienopyridines
▪ Although aspirin is effective in the setting of ACS, it is a relatively
weak platelet inhibitor that blocks platelet aggregation through only
one pathway.
▪ The thienopyridines clopidogrel and ticlopidine are antiplatelet agents
that mediate their antiplatelet effects through a blockade of ADP
P2Y12 receptors on platelets.
▪ Because ticlopidine is associated with the occurrence of neutropenia
that requires frequent monitoring of the complete blood count during
the first 3 months of use.
▪ Clopidogrel is the preferred thienopyridine for ACS and PCI patients.

ADR
▪ Diarrhea
▪ Nausea
▪ Dyspepsia
▪ Rash
▪ Abdominal pain
▪ Neutropenia, Thrombocytopenia, Thrombotic Thrombocytopenic
Purpura (TTP), and Aplastic Anemia.

Contraindications
▪ Increased risk of bleeding (i.e. frequent falls, gastrointestinal bleeds)
▪ History of hematological disease
▪ Severe liver disease
▪ History of allergic reaction to ticlopidine or any thienopyridine drug
such as clopidogrel
▪ Because of the increased risk of bleeding, patients taking ticlopidine
should discontinue the medication 10–14 days before surgery.
▪ Pregnancy and lactation

GP IIb/IIIa Receptor Inhibitors
▪ Abciximab is a first-line GP IIb/IIIa receptor inhibitor for patients
undergoing primary PCI who have not received fibrinolytics.
▪ It should not be administered for medical management of patients with
STE ACS who will not be undergoing PCI.
▪ Abciximab, in combination with aspirin, a thienopyridine, and UFH
reduced mortality and reinfarction without increasing the risk of major
bleeding.

MOA
GP IIb/IIIa receptor inhibitors block the final
common pathway of platelet aggregation,
namely, cross-linking of platelets by fibrinogen
bridges between the GP IIb/IIIa receptors on
the platelet surface.

ADR
▪ allergic reaction
▪ headache, back pain, nausea/vomiting
▪ dizziness/lightheadness/ fainting, and
▪ pain at the injection site.

Dose
GP IIb/IIIa Receptor
Inhibitors
Recommended Dose Duration of Therapy
Abciximab Bolus: 0.25mg/kg
Continuous: 0.125mg/kg/min
Continue 12h post
procedure
Tirofiban Bolus: 0.25mg/kg
Continuous: 0.125mg/kg/min
Continue 12-18h post
procedure
Eptifibatide Bolus: 180mcg/kg × 2 bolus
dose
Continuous: 2mcg/kg/min

1. Indirect Thrombin Inhibitors (Heparin)
▪ UFH, administered as an IV bolus followed by a continuous infusion, is
a first-line anticoagulant for treatment of patients with STE ACS, both
for medical therapy and for patients undergoing PCI.
▪ UFH binds to antithrombin and then inhibits the activity of clotting
factors Xa and IIa (thrombin).
▪ Anticoagulant therapy should be initiated in the emergency
department and continued for at least 48 hours in selected patients
who will be bridged over to receive chronic warfarin anticoagulation
following acute MI.
▪ If a patient undergoes PCI, UFH is discontinued immediately afterthe
procedure.

▪ For more than 40 years UFH has been the traditional anticoagulant
administered to patients with STE ACS for prevention of infarct
artery reocclusion.
▪ Other beneficial effects of anticoagulation in patients with ACS are
prevention of cardioembolic stroke and venous thromboembolism.
▪ LMWH, because their composition is mostly short saccharide
chain lengths, they preferentially inhibit factor Xa over factor IIa,
which requires larger chain lengths for binding and inhibition.
▪ Although the bleeding rates were increased in patients older than
75 years compared to younger patients.

▪ Fondaparinux is an indirect-acting specific inhibitor of factor Xa
that has recently been studied in the setting of STE ACS.
▪ Unlike UFH and LMWHs, fondaparinux does not cause heparin-
induced thrombocytopenia.

ADR
▪ A possible side effect of anticoagulants is excessive bleeding (haemorrhage),
because these medicines increase the time it takes for blood clots to form.
▪ Excessive bleeding
Signs of excessive bleeding can include:
 Passing blood in your urine, passing blood when you poo or having black poo
 Severe bruising, prolonged nosebleeds (lasting longer than 10 minutes)
 Bleeding gums, vomiting blood or coughing up blood
 Sudden severe back pain, difficulty breathing or chest pain
 In women, heavy or increased bleeding during your periods, or any other
bleeding from your vagina

▪ Diarrhoea or Constipation
▪ Feeling and being sick
▪ Indigestion
▪ Dizziness
▪ Headaches
▪ Rashes
▪ Itchy Skin
▪ Hair Loss
▪ Jaundice

Fondaparinux 2.5 mg SC OD 5mg (<50kg), 7.5mg (50-100),
10mg (>100kg) SC OD
0.25 s.c. once day

2. Direct Thrombin Inhibitors
 Direct thrombin inhibitors (DTIs) are a class of medication that act
as anticoagulants (delaying blood clotting) by directly inhibiting
the enzyme thrombin (factor II).
 Some are in clinical use, while others are undergoing clinical
development.
 Several members of the class are expected to replace heparin (and
derivatives) and warfarin in various clinical scenarios.
 Bivalent DTIs enjoy limited use in circumstances where heparin would
be indicated such as the acute coronary syndrome ("unstable angina"),
but cannot be used. As they are administered by injection
(intravenous, intramuscular or subcutaneous), they are less suitable for
long-term treatment.

Direct Thrombin Inhibitors types
Univalent Bivalent Allosteric Inhibitors
Hirudin
Bivalirudin
Lepirudin
Desirudin
Argatroban
Inogatran
Melagatran
Dabigatran
β-O4 lignin (SbO4L)

3. Vitamin K Epoxide reductase inhibitors or Vit. K
Antagonist
▪ Vitamin K antagonists (VKA) are a group of substances that
reduce blood clotting by reducing the action of vitamin K.
▪ They are used as anticoagulant medications in the prevention
of thrombosis, and in pest control, as rodenticides.
▪ deplete the active form of the vitamin by inhibiting the enzyme vitamin
K epoxide reductase and thus the recycling of the inactive vitamin K
epoxide back to the active reduced form of vitamin K.

1. Coumarins Derivatives
The most commonly used VKA is warfarin.
Others, Coumatetralyl, Phenprocoumon etc.
2. Indandiones
Pindone, chlorophacinone, and diphacinone are used as rodenticides.
Anisindione, fluindione, and phenindione are oral anticoagulant
medicines with actions similar to warfarin.

Nitrates
▪ Nitrates promote the release of nitric oxide from the endothelium, which
results in venous and arterial vasodilation at higher doses.
▪ Venodilation lowers preload and myocardial oxygen demand.
▪ Arterial vasodilation may lower blood pressure, thus reducing myocardial
oxygen demand.
▪ One SL NTG tablet (0.4 mg) should be administered every 5 minutes for
up to three doses to relieve myocardial ischemia.
▪ IV NTG is indicated in patients with ACS who do not have a
contraindication and who have persistent ischemic symptoms, heart failure,
or uncontrolled blood pressure.
▪ It should be continued for approximately 24 hours after ischemia is
relieved

▪ The most significant adverse effects of nitrates are tachycardia,
flushing, headache, and hypotension.
▪ Nitrate administration is contraindicated in patients who have received
oral phosphodiesterase- 5 inhibitors, such as sildenafil and vardenafil,
within the past 24 hours and tadalafil within the past 48 hours.

β-Blockers
▪ Aβ-blocker should be administered early in the care of patients with
STE ACS and continued indefinitely.
▪ In ACS, the benefit of β-blockers results mainly from the competitive
blockade of β1-adrenergic receptors located on the myocardium.
▪ β1-blockade produces a reduction in heart rate, myocardial
contractility, and blood pressure, decreasing myocardial oxygen
demand.
▪ In addition, the reduction in heart rate increases diastolic time, thus
improving ventricular filling and coronary artery perfusion.
▪ β-blockers reduce the risk for recurrent ischemic, infarct size, risk of
reinfarction, and occurrence of ventricular arrhythmias in the hours and
days following MI.

▪ The most serious side effects of β-blocker administration early in ACS
are hypotension, acute heart failure, bradycardia, and heart block.
▪ In patients in whom a major concern exists regarding a possible
intolerance to β-blockers, such as patients with bronchospastic
pulmonary disease, a short-acting β-blocker, such as metoprolol or
esmolol, initially should be administered IV.
▪ β-Blockers are continued indefinitely

Calcium Channel Blockers
▪ Administration of calcium channel blockers in the setting of STE ACS is reserved for
patients who have contraindications to β-blockers and is given for relief of ischemic
symptoms.
▪ Calcium channel blockers inhibit calcium influx into myocardial and vascular smooth
muscle cells, causing vasodilation.
▪ Although all calcium channel blockers produce coronary vasodilation and decrease
blood pressure, other effects are more heterogeneous between agents.
▪ Verapamil, diltiazem, and first-generation dihydropyridines also should be avoided in
patients with decompensated heart failure or LV dysfunction because these drugs can
worsen heart failure and potentially increase mortality secondary to their negative
inotropic effects.

EARLY PHARMACOTHERAPY FOR NSTE ACS

▪ In general, early pharmacotherapy for NSTE ACS is similar to that for
STE ACS with three exceptions:
1. Fibrinolytic therapy is not administered.
2. GP IIb/IIIa receptor blockers are administered to high-risk patients.
3. There are no standard quality performance measures for patients with
NSTE ACS with unstable angina (not diagnosed with MI).
▪ According to the ACC/AHA NSTE ACS practice guidelines, early
pharmacotherapy for NSTE ACS should include intranasal oxygen (if
oxygen saturation is <90%), SL NTG, aspirin, an oral β- blocker (IV β-
blocker optional), and an anticoagulant (UFH, LMWH [enoxaparin],
fondaparinux, or bivalirudin).

▪ Morphine is also administered to patients with refractory angina,
as described previously in Early Pharmacotherapy for STE ACS.
▪ IV NTG should be administered in selected patients without
contraindications.

SECONDARY PREVENTION FOLLOWING MI
▪ The long-term goals following MI are as follow:
1. Control modifiable CHD risk factors
2. Prevent development of systolic heart failure
3. Prevent recurrent MI and stroke
4. Prevent death, including sudden cardiac death
▪ Pharmacotherapy that has been proven to decrease mortality, heart
failure, reinfarction, or stroke should be initiated prior to hospital
discharge for secondary prevention.

▪ Guidelines from the ACC/AHA suggest that following MI from either STE or NSTE
ACS, patients should receive indefinite treatment with aspirin, a β-blocker, and an ACE
inhibitor.
▪ All patients should receive SL NTG or lingual spray and instructions for use in case of
recurrent ischemic chest discomfort.
▪ Clopidogrel should be considered for most patients, but the duration of therapy is
individualized according to the type of ACS.
▪ Newer therapies include eplerenone, an aldosterone antagonist for heart failure.
▪ For all ACS patients, treatment and control of modifiable risk factors, such as
hypertension, dyslipidemia, and diabetes mellitus, are essential.
▪ Most patients with CHD will require drug therapy for dyslipidemia, usually with a
statin

Aspirin
▪ Aspirin decreases the risk of death, recurrent MI, and stroke following MI.
▪ The clinical value of aspirin in secondary prevention of ACS and other
vascular diseases was demonstrated in a large number of clinical trials.
▪ The risk of major bleeding from chronic aspirin therapy is approximately
2% and is dose related. (Dose related)
▪ After an initial dose of 325 mg, chronic therapy with aspirin should be 75 to
81 mg once daily.
▪ AHA/ACC recommend 162–325 mg of aspirin once daily for at least 30
days
▪ To minimize the risk of bleeding combinations should be avoided unless the
combination is clinically indicated.

Thienopyridines
▪ For patients with NSTE ACS, clopidogrel decreases the risk of
developing death, MI, or stroke.
▪ The benefit derives primarily from reducing the rate of MI.
▪ Most patients with NSTE ACS should receive clopidogrel, in addition
to aspirin, for up to 12 months.
▪ The most common adverse effects in patients receiving clopidogrel are
rash (5%) and gastrointestinal upset (3%).

Anticoagulation
▪ Warfarin should be considered in selected patients following an ACS,
including patients with an LV thrombus, patients demonstrating
extensive ventricular wall-motion abnormalities on cardiac
echocardiogram, and patients with a history of thromboembolic disease
or chronic atrial fibrillation.

β-Blockers, Nitrates, and Calcium
Channel Blockers
▪ Current treatment guidelines recommend that, following an ACS, patients
should receive a β-blocker indefinitely, whether or not they have residual
symptoms of angina.
▪ benefit from β-blockers appears to be maintained for at least 6 years
following an MI.
▪ β-blockers should be avoided in patients with decompensated heart failure
from LV systolic dysfunction complicating an MI.
▪ All patients should be prescribed short-acting SL NTG or lingual NTG spray
to relieve any anginal symptoms when necessary and should be instructed on
its use.
▪ Chronic long-acting nitrate therapy has not been shown to reduce CHD
events following MI.

ACE Inhibitors and Angiotensin
Receptor Blockers
▪ ACE inhibitors should be initiated in all patients following MI to
reduce mortality, decrease reinfarction, and prevent development of
heart failure.
▪ The benefit of ACE inhibitors in patients with MI most likely derives
from their ability to prevent cardiac remodeling.
▪ Other proposed mechanisms include improvement in endothelial
function, reduction in atrial and ventricular arrhythmias, and promotion
of angiogenesis, leading to a reduction in ischemic events.
▪ The largest reduction in mortality is observed for patients with LV
dysfunction (low LVEF) or heart failure symptoms.

▪ Many patients cannot tolerate chronic ACE inhibitor therapy secondary
to adverse effects.
▪ However, trials have documented that the angiotensin receptor blockers
candesartan and valsartan improve clinical outcomes in patients with
heart failure.
▪ Although some data have suggested that aspirin use may decrease the
benefits of ACE inhibitor treatment, a systematic review of more than
20,000 patients demonstrated that ACE inhibitors improve outcome
irrespective of treatment with aspirin.

Aldosterone Antagonists
▪ Administration of an aldosterone antagonist, either eplerenone or
spironolactone, should be considered within the first 2 weeks following
MI in all patients already receiving an ACE inhibitor who have EF
≤40% and either heart failure symptoms or a diagnosis of diabetes
mellitus to reduce mortality.
▪ Aldosterone plays an important role in heart failure and MI because it
promotes vascular and myocardial fibrosis, endothelial dysfunction,
hypertension, LV hypertrophy, sodium retention, potassium and
magnesium loss, and arrhythmias.

Lipid-Lowering Agents
▪ The benefits of statins in patients with CAD for the prevention of total
mortality, cardiovascular mortality, and stroke.
▪ dietary counseling, LDL <100 mg/dL.
▪ A fibrate or niacin should be considered in selective patients with a low
high-density lipoprotein (HDL) cholesterol concentration (<40 mg/dL)
and/or a high triglyceride level (>200 mg/dL).
▪ use of gemfibrozil (600 mg twice daily) significantly decreased the risk
of nonfatal MI or death from coronary causes.
▪ Due to the increased risk of myopathy, gemfibrozil is not
recommended in patients receiving a statin.

Fish Oils (Marine-Derived ω-3 Fatty Acids)
▪ Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are ω-3
polyunsaturated fatty acids that are most abundant in fatty fish such as
sardines, salmon, and mackerel.
▪ Although the exact mechanism responsible for the beneficial effects of
ω-3 fatty acids has not been clearly elucidated, potential mechanisms
include triglyceride-lowering effects, antithrombotic effects,
retardation in the progression of atherosclerosis, endothelial relaxation,
mild antihypertensive effects, and reduction in ventricular arrhythmias.
▪ Adverse effects from fish oils include fishy after taste, nausea, and
diarrhea.

Other Modifiable Risk Factors
▪ Smoking cessation, control of hypertension, weight loss, and tight
glucose control for patients with diabetes mellitus, in addition to
treatment of dyslipidemia, are important treatments for secondary
prevention of CHD events.
▪ All patients with CAD should receive annual influenza vaccination.
▪ Hypertension should be strictly controlled to a target blood pressure
<130/80 and even lower, and to <120/80 in patients with LV
dysfunction according to recently published guidelines from AHA.
▪ Patients who are overweight should be educated on the importance of
regular exercise, healthy eating habits, and of reaching and maintaining
an ideal weight.

▪ diabetics have up to a fourfold increased risk of mortality compared
with non-diabetics, the importance of tight glucose control, as well as
other CHD risk factor modification, cannot be understated.

Therapeutic Drug Monitoring for Adverse Effects of
Pharmacotherapy for Acute Coronary Syndromes

EVALUATION OF THERAPEUTIC OUTCOMES
The monitoring parameters for efficacy of non-pharmacologic and
pharmacotherapy for both STE and NSTE ACS are similar:
 Relief of ischemic discomfort
 Return of ECG changes to baseline
 Absence or resolution of heart failure signs

References
1)Joseph. T. Dipiro, Pharmacotherapy: A pathophysiologic approach, seventh
edition
2)Eric. T. Herfindal, Textbook of Therapeutics : Drug and Disease
Management, Eight edition
3) Roger Walker, Clinical Pharmacy And Therapeutics, Fourth Edition

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