ACUTE CORONARY

SYNDROME
(ACS)
 Acute Coronary Syndrome (ACS)

• ACS  atherosclerotic plaque rupture:

a. with subsequent platelet adherence,
activation, aggregation,
b. activation of the clotting cascade.

• Formation of clot (fibrin and platelets).

 Pathophysiology
Spectrum of ACS
• ACSs  STEMI or non-STEMI and unstable angina

• ACS  diminished myocardial blood flow secondary to

an occlusive or partially occlusive coronary artery
thrombus.

• NSTEMI differs from UA in that ischemia is severe

enough to produce myocardial necrosis  release of a
detectable amount of biochemical markers (troponins T
or I and creatine kinase)
 Pathophysiology

Plaque Susceptible to Rupture

• Eccentric shape,
• Thin fibrous cap
• large fatty core,
• High inflammatory cells (macrophages and
lymphocytes)  thinning fibrous cap by MMP
• Limited amounts of smooth muscle.
 Pathophysiology
• Following plaque rupture  a partially occlusive or
completely occlusive thrombus (clot) forms on top of the
ruptured plaque.

• The thrombogenic contents of the plaque are exposed to

blood elements. Exposure of collagen and tissue factor
induce platelet adhesion and activation  release of
platelet-derived vasoactive substances, including ADP &
TXA2  vasoconstriction &potentiate platelet activation.

• A change in the conformation in the glycoprotein (GP)

IIb/IIIa surface receptors of platelets occurs that cross-links
platelets to each other through fibrinogen bridges.

• Inclusion of platelets gives the clot a WHITE appearance.

 Pathophysiology

• Simultaneously, the extrinsic coagulation cascade

pathway is activated as a result of exposure of blood
components to the thrombogenic lipid core and
endothelium, which are rich in tissue factor  production
of thrombin (factor IIa)  converts fibrinogen to fibrin
through enzymatic activity.

• Fibrin stabilizes the clot and traps red blood cells  give
the clot a RED appearance.

• The clot is composed of cross-linked PLATELET and

FIBRIN strands
 Pathophysiology

• Non-STEMI  A thrombus containing more platelets

than fibrin (“white” clot)  an incomplete occlusion
of the coronary lumen.

• STEMI  the vessel is completely occluded by a “re

d” clot (larger amounts of fibrin and red blood cells but
a smaller amount of platelets compared with a “white”
clot.

• Myocardial ischemia  the downstream embolization

of microthrombi and produce ischemia with eventual
necrosis.
 Pathophysiology
Ventricular Remodelling Following Acute MI
• Changes in the size, shape, and function of the left
ventricle and leads to cardiac failure.

• Neurohormonal factors (e.g., activation of the renin-

angiotensin aldosterone and sympathetic nervous
systems), hemodynamic factors, mechanical factors,
and changes in gene expression.

• Slow down or reverse ventricular remodeling through

neurohormonal blockage and/or through improvement
in hemodynamics (decreasing preload or afterload) 
ACE inhibitors, β-blockers, and aldosterone
antagonists .
 Pathophysiology

Complications
• Most common  Cardiogenic shock (Mortality almost
60%).
• HF, ventricular and atrial tachyarrhythmias,
bradycardia, heart block, pericarditis, stroke secondary
to left ventricular (LV) thrombus embolization, venous
thromboembolism, and LV freewall rupture.
• More than one-quarter of MI patients die, presumably
from ventricular fibrillation, prior to reaching the
hospital
 Clinical Presentation & Diagnosis

1. Symptoms & Physical Examination Findings

– Chest discomfort at least 20 minutes in duration. Radiate to the
shoulder, down the left arm, to the back, or to the jaw.
– Nausea, vomiting, diaphoresis, or shortness of breath.

2. Twelve Lead ECG

– 12-lead ECG should be obtained and interpreted.

3. Biochemical Markers
Troponin I or T and Creatinin Kinase (CKMB)
 Treatments

1. Early restoration of blood flow

2. Prevention of death and other complications

3. Prevention of coronary artery reocclusion

4. Relief of ischemic chest discomfort

 Treatments
A. Early Pharmacology Therapy for STEMI

• intranasal oxygen (if oxygen saturation is <90%),

sublingual (SL) followed by intravenous (IV) nitroglycerin
(NTG), aspirin, an IV β-blocker, unfractionated heparin
(UFH), and fibrinolysis in eligible candidates.
• Morphine is administered to patients with refractory
angina as an analgesic and a venodilator that lowers
preload.
FIGURE 1. Factors involved in platelet aggregation and the points of action (parallel lines) of
various antithrombotic and anticoagulant drugs. ADP=adenosine diphosphate; LMWHs=low-
molecular-weight heparins; UFH=unfractionated heparin (Long-term Care After
Percutaneous Coronary Intervention: Focus on the Role of Antiplatelet Therapy - GREGG
W. STONE, MD; HERBERT D. ARONOW, MD, MPH)
http://emcrit.org/images/acs%20path.jpg
 Treatments

1. Fibrinolytics
– The mortality benefit of fibrinolysis is highest with early
administration and diminishes after 12 hours.
– Non Fibrin Specific  Streptokinase
– Fibrin Specific  Alteplase, Reteplase, Tenecteplase
– Fibrin Specific is preferred over non spesific  open a greater
percentage of infarct arteries when measured in patients
undergoing emergent angiography
– Side effects  high risk for intracranial (alteplase, tenecteplase,
reteplase) and major bleeding (streptokinase)
 Treatments

2.a. Aspirin
• The preferred antiplatelet agent in the treatment of all
ACSs.
• Inhibition of the synthesis of thromboxane A2 through an
irreversible inhibition of platelet cyclooxygenase-1.
• Initial dose 160 to 325 mg/day
• long term 75 to 150 mg/day
• Side Effects  Potential of GI Bleeding  lower doses
<325 mg/day  lower rate of GI bleeding
• Monitor also  Renal function
 Treatments

2.b. Thienopyridines
• Clopidogrel is recommended if have an aspirin allergy.
• Blockade of ADP receptors on platelets.
• Ticlopidine  neutropenia  frequent monitor of CBC
(first 3 months)  clopidogrel is the preferred.
• For PCI  300- to 600-mg loading dose 75 mg/day
maintenance dose (combination with aspirin)
• Side effects of clopidogrel are nausea, vomiting, and
diarrhea. Bleeding is the most serious
 Treatments

3. Glycoprotein IIB/IIIA Receptor Inhibitors

• GP IIb/IIIa receptor inhibitors block the cross-linking of
platelets by fibrinogen bridges between the GP IIb and
IIIa receptors on the platelet surface
• Abciximab is a first-line GP IIb/IIIa receptor inhibitor for
patients undergoing primary PCI who have not received
fibrinolytics.
• Abciximab, in combination with aspirin, a thienopyridine,
and UFH  reduce the risk of reinfarction and need for
repeat PCI in ST-segment-elevation ACS clinical trials.
 Treatments

4. Anticoagulants
• UFH binds to antithrombin and then to clotting factors Xa
and IIa (thrombin).
• UFH (continuous infusion)  a first-line anticoagulant for
the treatment of patients with STEMI (medical therapy
and PCI).
• The dose of the UFH infusion is adjusted frequently to a
target activated partial thromboplastin time (aPTT)  60
– 80 seconds.
• Caution: Heparin induced trombocytopenia
 Treatments

5. Nitrates
• Release NO from the endothelium, which results in venous and
arterial vasodilation
• Venodilation lowers preload and myocardial oxygen demand.
• Arterial vasodilation may lower blood pressure, thus reducing
myocardial oxygen demand.
• Arterial vasodilation also relieves coronary artery vasospasm,
dilating coronary arteries to improve myocardial blood flow and
oxygenation.
• IV NTG then should be initiated in all patients with an ACS who do
not have a contraindication and who have persistent ischemic
symptoms, heart failure, or uncontrolled blood pressure, and should
be continued for approximately 24 hours after ischemia is relieved.
 Treatments

6. Beta Blockers
• β1-Blockade produces a reduction in heart rate, myocardial
contractility, and blood pressure, decreasing myocardial oxygen
demand.
• The reduction in heart rate increases diastolic time, thus improving
ventricular filling and coronary artery
• IV bolus doses or oral doses of a β-blocker should be administered
early in the care of patients with STEMI and then an oral β-blocker
continued indefinitely.
• Landmark clinical trials have established the role of early β-blocker
therapy in reducing MI mortality
 Treatments

7. Calcium Channel Blockers

• Calcium channel blockers inhibit calcium influx into
myocardial and vascular smooth muscle cells, causing
vasodilatation.
• Administration of CCBs in the setting of STEMI is
reserved for patients who have contraindications to β-
blockers and is used for relief of ischemic symptoms.
 Treatments

B. Early Pharmacology Therapy for Non-STEMI

• Early pharmacotherapy for non-STEMI is similar to that
for STEMI.

1. Fibrinolytic therapy is NOT administered.

2. Combination of clopidogrel aspirin to most patients.
3. GP IIb/IIIa receptor blockers  high-risk patients for
medical therapy as well as for PCI patients.

4. There are no standard quality indicators for patients with

non-STEMI who are not diagnosed with MI
 Treatments

1. Fibrinolytic Therapy
• Fibrinolytic therapy is NOT indicated in any patient with
non-STEMI, even those who have positive biochemical
markers (e.g., troponin) that indicate infarction.

2. Aspirin
• Aspirin reduces the risk of death or developing MI by
about 50% (compared with no antiplatelet therapy) in
patients with non-STEMI.
• Therefore, aspirin remains the cornerstone of early
treatment for all ACSs.
• Similar dose of non-STEMI and STEMI. Aspirin is
continued indefinitely.
 Treatments

3. Thienopyridines
• An addition clopidogrel started on the first day of
hospitalization as a 300- to 600-mg loading dose
followed the next day by 75 mg/day orally is
recommended for most patients.
• In CURE, the risk of major bleeding was increased in
patients receiving clopidogrel plus aspirin compared with
aspirin alone.
 Treatments

4. Glycoprotein IIB/IIIA Receptor Inhibitors

• GP IIB/IIIA inhibitor  high risk non-STEMI patients as
medical therapy, PCI patients, continued or recurrent
ischemia despite treatment with aspirin and an
anticoagulant
• The risk of thrombocytopenia with tirofiban and
eptifibatide appears to be lower than that with abciximab.
• Bleeding risks appear similar among agents.
• Major bleeding with the combination of aspirin, heparin,
and a GP IIb/IIIa inhibitor is higher (approximately 3% to
4%) than using a heparin plus aspirin (<2%).
 Treatments

5. Anticoagulants
• Either UFH or LMWHs should be administered to
patients with non- STEMI.
• Therapy should be continued for up to 48 hours or until
the end of the angiography or PCI procedure.
• In patients initiating warfarin therapy, UFH or LMWHs
should be continued until the international normalization
ratio (INR) with warfarin is in the therapeutic range.
• The addition of UFH to aspirin  33% reduction in the
risk of death or MI at 6 weeks with UFH plus aspirin
compared with aspirin alone.
 Treatments

5. Anticoagulants
• Because LMWHs are eliminated renally  UFH for
patients with CrCl <30 mL/min.
• Administration of LMWHs should be avoided in dialysis
patients.
• UFH is monitored and the dose adjusted to a target
aPTT, whereas LMWHs are administered by a fixed,
weight-based dose.
 Treatments
6. Nitrates
• SL followed by IV NTG  all patients with non-STEMI
ACS in the absence of contraindications. IV NTG is
continued for +/- 24 hours after ischemia relief.
7. Beta Blockers
• IV followed by oral β-blockers  all patients with non-
STEMI in the absence of contraindications. β-Blockers
are continued indefinitely.
8. Calcium Channel Blockers
• CCBs NOT given to most patients with ACS.
• Second-line treatment  for pts contraindications to β-
blockers & continued ischemia despite β-blocker+nitrate.
• Amlodipine, diltiazem, or verapamil is preferred.
 Treatments

C. Secondary Prevention Following MI

The long-term goals following MI are to

1. Control modifiable CHD risk factors
2. Prevent the development of systolic heart failure
3. Prevent recurrent MI and stroke
4. Prevent death, including sudden cardiac death
 Treatments

1. Aspirin
• Aspirin decreases the risk of death, recurrent MI, and
stroke following MI.
2. Clopidogrel
• For patients with non-STEMI, clopidogrel decreases the
risk of developing either death, MI, or stroke. The benefit
is primarily in reducing the rate of MI.
• The ACC/AHA guidelines suggest a duration of therapy
of 9 months because this was the average duration of
treatment in the CURE trial.
 Treatments
3. Anticoagulants
• Residual thrombus at the site of plaque rupture even
months following an MI  anticoagulants
• The use of warfarin in combination with aspirin was
associated with an increased risk of minor and major
bleeding.
4. Beta Blockers, Nitrates, & Ca Channel Blockers
• Following an ACS, patients should receive a β-blocker indefinitely
whether they have residual symptoms of angina or not.
• Although β-blockers should be avoided in patients with
decompensated heart failure from LV systolic dysfunction
complicating an MI, clinical trial data suggest that it is safe to initiate
β-blockers prior to hospital discharge in these patients once heart
failure symptoms have resolved.
 Treatments
5. ACEI & ARB
• ACE inhibitors should be initiated in all patients following
MI to reduce mortality, decrease reinfarction, and
prevent the development of heart failure.
• The benefit of ACE inhibitors in patients with MI most
likely comes from their ability to prevent cardiac
remodeling.
 Treatments
6. Lipid Lowering Agents
• The National Cholesterol Education Program (NCEP)
Adult Treatment Panel recommendations, all patients
with CAD should receive dietary counseling and
pharmacologic therapy in order to reach a LDL <00
mg/dL, with statins being the preferred agents to lower
LDL
7. Fish Oil (Marine-derived Omega-3 Fatty Acids)
• A diet high in EPA plus DHA or supplementation with
these fish oils reduces the risk of cardiovascular
mortality, reinfarction, and stroke in patients who have
experienced an MI.
 Treatments
8. Aldosteron Antagonists
• Either eplerenone or spironolactone, should be
considered within the first 2 weeks following MI in all
patients already receiving an ACE inhibitor who have an
EF of 40% or less and either heart failure symptoms or a
diagnosis of diabetes mellitus to reduce mortality.
9. 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.
 Treatments

10. Therapies NOT Useful & Potentially Harmful

• HRT to all women following MI does not prevent
recurrent CHD events and may be harmful.
• Administration of vitamin E for secondary prevention is
ineffective following MI.
• Not effective  vitamins A, C, or E, multivitamins with
folic acid, or a combination of antioxidants to prevent
CVDs.
 Evaluation of Therapeutics Outcomes

Parameters for efficacy of nonpharmacologic and

pharmacotherapy for both STEMI and non-STEMI:

1. Relief of ischemic discomfort

2. Return of ECG changes to baseline
3. Absence or resolution of heart failure signs

The most common adverse reactions from ACS

therapies are hypotension and bleeding.