Acute coronary

syndromes
 DEFINITIONS

• Acute coronary syndromes (ACSs) include all clinical

syndromes compatible with acute myocardial ischemia
resulting from an imbalance between myocardial oxygen
demand and supply

• results primarily from diminished myocardial blood flow

secondary to an occlusive or partially occlusive coronary
artery thrombus
 Acute Coronary Syndrome (ACS)

• Definition: The spectrum of acute ischemia related syndromes

ranging from UA to MI with or without ST elevation that are
secondary to acute plaque rupture or plaque erosion.

[----UA---------NSTEMI----------STEMI----]
Unstable
NSTEMI STEMI
Angina
Non-occlusive
thrombus Complete thrombus
Non occlusive sufficient to cause occlusion
thrombus tissue damage & mild
myocardial necrosis ST elevations on
Non specific ECG or new LBBB
ECG ST depression +/-
T wave inversion on Elevated cardiac
Normal cardiac ECG enzymes
enzymes
Elevated cardiac More severe
enzymes symptoms
 PATHOPHYSIOLOGY

• The formation of atherosclerotic plaques is the underlying

cause of coronary artery disease (CAD) and ACS in most
patients.

• Endothelial dysfunction leads to the formation of fatty streaks

in the coronary arteries and eventually to atherosclerotic
plaques.

• The cause of ACS in more than 90% of patients is rupture,

fissuring, or erosion of an unstable atheromatous plaque
 Pathophysiology of ACS
• Acute coronary syndromes can also be due to secondary
causes
– Thyrotoxicosis
– Anemia
– Tachycardia
– Hypotension
– Hypoxemia
– Aterial inflammation (infection, arteritis)
 CLINICAL PRESENTATION

• midline anterior chest discomfort (most often occurring at rest)

• The discomfort may radiate to the shoulder, down the left arm,
to the back, or to the jaw

• Accompanying symptoms may include nausea, vomiting,

diaphoresis, or shortness of breath
 ACS clinical presentation

Is a "clinical syndrome
characterized by discomfort in
the chest, jaw, shoulder, back, or
arm"

8
 Diagnosis of ACS
• At least 2 of the following

– History ( angina or angina

equivalent)

– Acute ischemic ECG changes

– Typical rise and fall of cardiac

markers

• troponin I or T, CK-MB

– Absence of another identifiable

etiology
 Treatment of ACS; Aspirin

• Aspirin is an antiplatelet agent that initiates the irreversible

inhibition of cyclooxygenase, thereby preventing platelet
production of thromboxane A2 and decreasing platelet
aggregation

• Administration of ASA in ACS reduces cardiac endpoints

ACC/AHA Guidelines for Aspirin Therapy

• Aspirin should be given in a dose of 75-325 mg/day to all

patients with ACS unless there is a contraindication (in which
case, clopidogrel should be given)
 Treatment of ACS; Nitrates

• Nitroglycerin is considered a cornerstone of anti-

anginal therapy, despite little objective evidence for
its benefit
• Benefit is thought to occur via reduction in
myocardial O2 demand secondary to venodilation
induced reduction in preload as well as coronary
vasodilation and afterload reduction
• Titrate to relief of chest pain; chest pain = death of
myocardial cells
• No documented mortality benefit
 Treatment of ACS; Beta Blockers

• Beta Blockers reduce myocardial oxygen demand by reducing

heart rate, contractility, and ventricular wall tension

• Administration of beta blockers in ACS reduces cardiac

endpoints
 Beta Blocker Trials

• metoprolol
• Beta Blocker Heart Attack Trial (propranolol)
• Esmolol vs. placebo
• Carvedilol vs. placebo
• Propranolol vs. placebo
– Overall, treatment with beta blockers reduces primary
endpoints when compared to placebo
AHA/ACC Guidelines for Beta Blocker Therapy

• Intravenous beta blockers should be used initially in all

patients (without contraindication) followed by oral beta
blockers with the goal being decrease in heart rate to 60 beats
per minute

• A combination of beta blockers and nitrates can be viewed as

first line therapy in all patients with ACS
 Treatment of ACS; Heparin

• Heparin (unfractionated heparin or UFH) has traditionally

been the mainstay of therapy in acute coronary syndromes as
its efficacy has been documented in several large, randomized
trials
• Heparin Trials
– UFH therapy generally results in an important clinical
benefit when compared to placebo.
– It is more effective when given in continuous infusion
rather than intermittent boluses
 Treatment of ACS; LMWH

• More recent studies indicate that low molecular weight heparin

is also effective in the reduction of end points such as
myocardial infarction or death

• Some studies report that LMWH, when used in combination

with ASA, may be superior to continuous infusion of Heparin

(LMWH + ASA VS Continuous Heparin)

ACC/AHA Guidelines for Heparin Therapy

• All patients with acute coronary syndromes should be treated

with a combination of ASA (325 mg/day) and heparin (bolus
followed by continuous infusion with goal of PTT 1-2.5X
control) or ASA and low molecular weight heparin unless one
of the drugs is contraindicated
 Treatment of ACS; ACE-I

• The best documented mechanism by which these agents act is

to reduce ventricular remodeling over days to weeks after
myocardial damage.

– However, there is data that a mortality benefit exists when

these agents are used early in the course of ACS

– Administration of ACE-I in ACS reduces cardiac endpoints

 AHA/ACC Guidelines for ACE-I Therapy

• ACE-I should be administered to all patients in the first 24

hours of ACS provided hypotension and other clear cut
contraindications are absent
 Treatment of ACS; Statins

• Statins may be of benefit in ACS

• Possible mechanisms include plaque stabilization, reversal of

endothelial dysfunction, decreased thrombogenicity, and
reduction of inflammation
Treatment of ACS; GP IIB / IIIA Inhibitors

• More potent inhibition of platelet aggregation may be of

importance in patients with ACS that is associated with
unstable coronary lesion and thrombus formation.

– This can be achieved by the use of GP IIB / IIIA inhibitors

• Administration of GP IIB/IIIA inhibitors reduces cardiac

endpoints
 AHA/ACC Guidelines for use of IIBIIIA
inhibitors

• GP IIB/IIIA inhibitor should be administered to all patients in

whom a percutaneous intervention is planned (in addition to
heparin/ASA)

• Eptifibatide or Tirofiban should be administered to patients

with ACS in whom PCI (percutaneous coronary intervention)
is not planned if other high risk features are present (TIMI risk
score >3)
 TIMI Risk Score

• Age >65 yrs

• Daily ASA Therapy (>7 days prior to event)

• Symptoms of Unstable Angina

• Documented CAD (stenosis > 50%)

• 3 or more traditional cardiac risk factors

• Elevated cardiac enzymes

• ECG changes
 TIMI Risk Score

• Score of 3 or less = low risk

• Score of 4-5 = intermediate risk (use Gp IIB/IIIA inhibitor)

• Score of 6-7 = high risk (use Gp IIB/IIIA inhibitor)

 Treatment of ACS; Clopidogrel

• Clopidogrel is a potent antiplatelet agent

• It should be administered to all patients who cannot take ASA

• Give 300 mg loading dose followed by 75 mg/day

 AHA/ACC Guidelines for Clopidogrel

• Clopidogrel should be administered to patients who cannot

take ASA because of hypersensitivity or gastrointestinal
intolerance
• In hospitalized patients in whom an early, noninterventional
approach is planned, clopidogrel should be added to ASA as
soon as possible on admission and administered for at least 1
month and up to 9 months.
• Do not use clopidogrel if there is any possibility patient may
be candidate for CABG (coronary artery bypass graft surgery)