Acute Coronary syndrome

Dr. Hayder Ch. Assad

 Acute coronary syndrome
Acute coronary syndrome (ACS) is an umbrella term that includes patients
who present with either
unstable angina (UA) or
acute myocardial infarction (AMI) [consisting of ST segment elevation
myocardial infarction (STEMI) or nonST segment elevation myocardial
infarction (NSTEMI)]
Unstable angina is characterized by rapidly worsening angina, angina on
minimal exertion or angina at rest in the absence of myocardial damage
In contrast MI occurs when symptoms occur at rest and there is evidence of
myocardial necrosis, as demonstrated by an elevation in cardiac biomarkers
[troponins (I or T) or creatine kinase myocardial band (CK-MB)] that
released from the necrotic myocytes into the bloodstream
 Etiology And Pathology
Endothelial dysfunction, inflammation, and the formation of fatty
streaks contribute to the formation of atherosclerotic coronary
artery plaques, the underlying cause of CAD.
The predominant cause of ACS in more than 90% of patients is
atheromatous plaque rupture.
Once ruptured, the thrombogenic components of the plaque
consisting of collagen and tissue factor are exposed.
This promotes activation of the platelet cascade, ultimately
leading to the formation of a clot or thrombus as well as ischemia
in the corresponding myocardial area
 Etiology And Pathology
In patients with UA, the coronary lesion demonstrates little
thrombosis.
In patients with NSTEMI, there exists partial thrombotic
occlusion.
For STEMI, there exists total thrombotic occlusion .
It is important to highlight that 80% of patients presenting with
ACS have two or more active plaques.
 Ventricular Remodeling Following an Acute MI
Ventricular remodeling is a process that occurs in several
cardiovascular (CV) conditions including HF and following an MI.
It is characterized by left ventricular dilation and reduced
pumping function of the left ventricle, leading to cardiac failure.
Because HF represents one of the principal causes of mortality
and morbidity following an MI, preventing ventricular remodeling
is an important therapeutic goal.
ACE inhibitors, ARBs, -blockers, and mineralocorticoid receptor
antagonists (MRAs) are all agents that slow down or reverse
ventricular remodeling .
 Clinical Presentation
Hallmark symptoms for ACS consist of
increasing frequency of exertional angina or chest pain at
rest,
new-onset severe chest discomfort, or
increasing angina with a duration exceeding 20 minutes.
The pain is typically midline anterior chest discomfort that can
radiate to the left arm, back, shoulder, or jaw and
may be associated with diaphoresis, dyspnea, nausea, and
vomiting as well as unexplained syncope.
 Clinical Presentation
Patients with STEMI will usually complain of unrelenting chest
pain
whereas patients with UA or NSTEMI will present with either
angina at rest, new-onset (2 months or less) angina, or angina that
increases in frequency, duration, or intensity.
Presentation may differ by sex and age.
Men commonly complain of chest pain, whereas women often
present with nausea and diaphoresis.
Painless or silent MI is particularly common in older patients or
those with diabetes mellitus (and women).
If syncope occurs, it is usually due to an arrhythmia or profound
hypotension.
 Diagnosis
A-ECG :
should be obtained within 10 minutes of patient presentation . Key
findings indicating myocardial ischemia or MI are ST segment
elevation (in STEMI), ST-segment depression, and T-wave
inversion (in NSTEMI).
Additionally, the ECG is helpful in determining the location of an
infarction (e.g., anterior, lateral, inferior, posterior).
An anterior wall infarction carries a worse prognosis than an
inferior or lateral wall infarction because it is more commonly
associated with development of left ventricular failure and
cardiogenic shock
 Clinical diagnosis of ACS
12 lead ECG
Non diagnostic Diagnostic

serial ECGs at
15- to 30-min
intervals ST elevation ST segment
during the or new LBBB depression or T
first hour wave inversion
-Measure serial
cardiac troponin T TROPONIN T
at presentation and
36 h after
symptom onset (I)
STEMI + -
NSTEMI UA
 Laboratory Changes
When a cardiac cell is injured, enzymes
are released into the circulation.
The measurement of these sensitive and
specific enzymes (troponins T or I and
creatine kinase [CK]) is confirmed the
diagnosis of AMI
Typically, a blood sample is obtained
once in the emergency department, and
then 6 to 9 hours later, and in patients at
a high suspicion of MI but in whom
previous measurements did not reveal
elevations in biomarkers, 12 to 24
hours after.
 Desired Outcomes
Short-term desired outcomes in a patient with ACS are:
a) 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 UA);
b) prevention of death and other MI complications;
c) prevention of coronary artery reocclusion; and as evidence of
restoration of coronary artery blood flow;
d) relief of ischemic chest discomfort; and
e) resolution of ST-segment and T-wave changes on the ECG.
Long-term desired outcomes are control of CV risk factors,
prevention of additional CV events, including reinfarction, stroke,
and HF, and improvement in quality of life.
 Treatment
The primary strategy for patients with an occluded coronary
artery (STEMI) is the restoration of coronary flow with either
by
fibrinolytic agent or
percutaneous coronary intervention( PCI).
If the coronary artery is patent (UA and NSTEMI), then
fibrinolysis is unnecessary and probably harmful, although PCI
may still be appropriate
 Nonpharmacological Therapy
1. Nonpharmacological Therapy for STEMI
For patients with STEMI, primary PCI (with either balloon
angioplasty or stent placement) is the treatment of choice for
reestablishing coronary artery blood flow when the patient with
STEMI presenting within 12 hours of the onset of chest
discomfort .
Primary PCI may be associated with a lower mortality rate than
fibrinolytic drugs, possibly because PCI opens >90% of coronary
arteries compared with <60% opened with fibrinolytics.
The risks of major bleeding are also lower with PCI than with
fibrinolysis.
Nonpharmacological Therapy
PCI in NSTE ACSs
The most recent ACCF/AHA clinical practice guidelines
recommend coronary angiography with either PCI or coronary
artery bypass graft (CABG) surgery revascularization as an
early treatment (early invasive strategy) for patients with NSTE
ACS at an elevated risk for death or MI, including those with a
high risk score or patients with refractory angina, acute HF,
other symptoms of cardiogenic shock, or arrhythmias
 Pharmacological Therapy
Early Pharmacotherapy for STEMI
Early pharmacologic therapy for patients with STEMI should
include:
1. Oxygen 5. Antiplatelet therapy
2. Morphine 6. Anticoagulant therapy
3. Nitrate 7. -Adrenergic Blockers
4. Fibrinolytic therapy 8. Statin
Statin
 Pharmacological Therapy
Early Pharmacotherapy for STEMI
Early pharmacologic therapy for patients with STEMI should
include:
1. Oxygen: (if oxygen saturation is <90%).
Morphine:
Prompt management of pain is an important measure to
minimize myocardial oxygen demand associated with pain and
anxiety.
Morphine is the analgesic of choice.
Morphine is administered as an analgesic and a venodilator
that lowers preload, but it does not reduce mortality.
 Pharmacological Therapy
3-Nitrate
Immediately upon presentation, one sublingual nitroglycerin
(NTG) tablet should be administered every 5 minutes for up to
three doses.
Intravenous NTG should be initiated (unless C/I) in all patients
with an ACS who have persistent ischemic symptoms, heart
failure, or uncontrolled high blood pressure.
The usual dose is 5 to 10 mcg/min by continuous infusion, titrated
up to 100 mcg/min until relief of symptoms or limiting side
effects (eg, headache or hypotension)
Treatment should be continued for about 24 hours after
ischemia is relieved .
 Early Pharmacotherapy for STEMI
4-Fibrinolytic Therapy
In the absence of contraindications, a fibrinolytic agent should be given to
patients with STEMI presenting within 12 hours of the onset of chest
discomfort when it is anticipated that primary PCI cannot be performed.
In patients who present within 12 to 24 hours of symptom onset, fibrinolytic
therapy is reasonable for patients with STEMI if there is clinical and/or ECG
evidence of ongoing.
Fibrin-specific agent (alteplase, reteplase, tenecteplase) is preferred over the
non-fibrin-specific agent streptokinase.
Fibrin-specific agents open a greater percentage of infarct arteries
 5- Antiplatelet
Immediate administration of aspirin 162 to 325 mg is indicated
for all patients with ACS.
In the acute setting, aspirin should be chewed because it is
absorbed more quickly
Patients undergoing PCI not previously taking aspirin should
receive 325 mg nonenteric-coated aspirin.
A daily maintenance dose of 75 to 162 mg is recommended
thereafter and should be continued indefinitely to inhibit the 10%
of the total platelet pool that is regenerated daily
 Antiplatelet therapy
Clopidogrel, prasugrel, and ticagrelor block a subtype of ADP
receptor (the P2Y12 receptor) on platelets, preventing binding of
ADP to the receptor and subsequent expression of platelet GP
IIb/IIIa receptors, reducing platelet aggregation.
Current guidelines recommend initiating dual antiplatelet
therapy with aspirin and a thienopyridine.
Clopidogrel (300600 mg loading dose followed by 75 mg daily)
should be added to aspirin regardless of whether the patient
undergoes reperfusion with fibrinolytic therapy.
The duration of P2Y12 inhibitors for a patient undergoing PCI
(either STE MI or NSTE ACS) is at least 12 months for patients
receiving either a bare metal or drug-eluting stent.
 Antiplatelet therapy
In patients receiving fibrinolysis, early therapy with clopidogrel
75 mg once daily during hospitalization and up to 28 days
reduces mortality and reinfarction without increasing risk of
major bleeding.
Clopidogrel is preferred P2Y12 inhibitor added to ASA and
should be continued for at least 14 days (and up to 1 year) for
patients presenting with STE MI who do not undergo
reperfusion therapy with either primary PCI or fibrinolysis.
If CABG surgery is planned, withhold clopidogrel and
ticagrelor for 5 days, and prasugrel at least 7 days, to reduce risk
of postoperative bleeding
 Home work

What is the differences between Clopidogrel, prasugrel, and

ticagrelor?
What is the clinical significant of interaction between PPI
and clopidogrel ?
 Antiplatelet therapy
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 and IIIa receptors on the
platelet surface.
Abciximab,eptifibatide, or tirofiban may be administered in
patients with STE MI undergoing primary PCI who are
treated with UFH.
Do not administer GP IIb/IIIa inhibitors to patients with STE MI
who will not be undergoing PCI or patients receive bivalirudin
as anticoagulant
Bleeding is the most significant adverse effect.
 6- Anticoagulants
For patients undergoing primary PCI, either UFH or bivalirudin
is preferred, whereas for fibrinolysis, UFH, enoxaparin, or
fondaparinux may be administered.
UFH initial dose for primary PCI is 50 to 70 units/kg IV bolus if a
GP IIb/IIIa inhibitor is planned and 70 to 100 U/kg IV bolus if no
GP IIb/IIIa inhibitor is planned.
UFH initial dose with fibrinolytics is 60 U/kg IV bolus (maximum
4000 units), followed by constant IV infusion of 12 U/kg/h
(maximum 1000 U/h). Adjust the UFH infusion dose frequently to
maintain a target activated partial thromboplastin time (aPTT) of
1.5 to 2 times control (5070 seconds).

Enoxaparin dose is 1 mg/kg subcutaneous (SC) every 12 hours
For patients with STE MI receiving fibrinolytics, enoxaparin 30
mg IV bolus is followed immediately by 1 mg/kg SC every 12
hours .
Bivalirudin dose for PCI in STE MI is 0.75 mg/kg IV bolus,
followed by 1.75 mg/ kg/h infusion.
Fondaparinux dose is 2.5 mg IV bolus followed by 2.5 mg SC
once daily starting on hospital day 2
What is the differences between UFH and DTI ? Which is better in MI ? Home
work
 Anticoagulants
For patients undergoing PCI, anticoagulation is discontinued
immediately following the PCI procedures.
In patients receiving an anticoagulant plus a fibrinolytic, UFH is
continued for a minimum of 48 hours and
if either enoxaparin or fondaparinux is selected, those agents are
continued for the duration of hospitalization, up to 8 days.
In patients who do not undergo reperfusion therapy, it is
reasonable to administer anticoagulant therapy for up to 48 hours
for UFH or for the duration of hospitalization for enoxaparin or
fondaparinux.
 7- -Adrenergic Blockers
If no contraindications, administer a -blocker early (within the
first 24 hours) and continue indefinitely.
Benefits result from blockade of 1 receptors in the myocardium,
which reduces heart rate, myocardial contractility, and BP, thereby
decreasing myocardial oxygen demand.
Reduced heart rate increases diastolic time, thus improving
ventricular filling and coronary artery perfusion.
-Blockers reduce risk for recurrent ischemia, infarct size,
reinfarction, and ventricular arrhythmias.
 -Adrenergic Blockers
Usual doses of -blockers, with target resting heart rate of
50 to 60 beats/min:
Metoprolol: 5 mg by slow (over 12 minutes) IV bolus,
repeated every 5 minutes for total initial dose of 15 mg. Follow
in 1 to 2 hours by 25 to 50 mg orally every 6 hours.
Propranolol: 0.5 to 1 mg slow IV push, followed in 1 to 2
hours by 40 to 80 mg orally every 6 to 8 hours.
Atenolol: 5 mg IV dose, followed 5 minutes later by a second 5
mg IV dose, then 50 to 100 mg orally once daily beginning 1 to
2 hours after the IV dose.
 -Adrenergic Blockers
The most serious side effects early in ACS include hypotension,
acute HF, bradycardia, and heart block.
Initial acute administration of -blockers is not appropriate for
patients presenting with acute HF but may be attempted in most
patients before discharge after treatment of acute HF.
Continue -blockers for at least 3 years in patients with normal
LV function and
Continue indefinitely in patients with LV systolic dysfunction
and LVEF of 40% or less.
8- Statins
Administer a high-intensity statin, either atorvastatin 80 mg or
rosuvastatin 40 mg, to all patients prior to PCI (regardless of
prior lipid-lowering therapy) to reduce the frequency of
periprocedural MI following PCI.

9-Calcium Channel Blockers

After STE MI, calcium channel blockers (CCBs) are used for relief
of ischemic symptoms in patients who have contraindications to -
blockers.
There is little clinical benefit beyond symptom relief, so avoid
CCBs in acute management of all ACSs unless there is a clear
symptomatic need or contraindication to -blockers.
 Early Pharmacotherapy For NSTE ACS
intranasal oxygen, SL NTG, aspirin, and an anticoagulant (UFH,
enoxaparin, fondaparinux, or bivalirudin).
High-risk patients should proceed to early angiography and may receive a
GP IIb/ IIIa inhibitor (optional with either UFH or enoxaparin but should be
avoided with bivalirudin).
Administer a P2Y12 inhibitor to all patients.
Give IV -blockers and IV NTG to select patients.
Initiate oral -blockers within the first 24 hours in patients without
cardiogenic shock.
Give morphine to patients with refractory angina, as described previously.
Fibrinolytic therapy is never administered in NSTE ACS.
 Secondary Prevention Following MI
Start pharmacotherapy that has been proven to decrease
mortality, HF, reinfarction or stroke, and stent thrombosis prior to
hospital discharge for secondary prevention.
1. Antiplatelet
2. ACE-I
3. -blocker
4. Statin
5. Mineralocorticoid receptor antagonist
6. Nitrate
 Secondary Prevention Following MI
After MI from either STE MI or NSTE ACS, all patients should
receive indefinite treatment with aspirin (or clopidogrel if
aspirin contraindications), an ACE inhibitor, and a high-
intensity statin for secondary prevention of death, stroke, or
recurrent infarction.
Start ACE inhibitors and continue indefinitely in all patients after
MI to reduce mortality, decrease reinfarction, and prevent HF.
Most patients with CAD ((not just those with ACS or HF) benefit
from an ACE inhibitor.
 Secondary Prevention Following MI
Captopril could be given on postinfarction day 2 or 3, beginning
with a test dose of 6.25 mg and then titrated to a maintenance
dosage of 25 to 50 mg three times a day
The BP should be monitored closely, with systolic BP maintained
greater than 90 mm Hg. Renal function and serum potassium
levels should be monitored closely during the first few months of
therapy
Captopril: 6.25-12.5 mg initially; target dose 50 mg BID or TID
Enalapril: 2.5-5 mg initially; target dose 10 mg BID
Lisinopril: 2.5-5 mg initially; target dose 10 to 20 mg QD
Ramipril: 1.25-2.5 mg initially; target dose 10 mg QD
 Secondary Prevention Following MI
An angiotensin receptor blocker may be prescribed for patients
with ACE inhibitor cough and a low LVEF and HF after MI:
Candesartan: 4 to 8 mg initially; target dose 32 mg once daily
Valsartan: 40 mg initially; target dose 160 mg twice daily
Continue a -blocker for at least 3 years in patients without HF
or an ejection fraction of 40% or less and indefinitely in patients
with LV systolic dysfunction or HF symptoms.
The benefits of -blockers in reducing reinfarction and mortality
outweigh the risk, even in patients with asthma, depression,
insulin-dependent diabetes, severe peripheral vascular disease,
first-degree heart block, and moderate left ventricular dysfunction
 Secondary Prevention Following MI
To reduce mortality, consider a mineralocorticoid receptor
antagonist (eplerenone or spironolactone) within the first 7 days
after MI in all patients already receiving an ACE inhibitor (or
ARB) and a -blocker and have an LVEF of 40% or less and either
HF symptoms or diabetes mellitus. The drugs are continued
indefinitely.
Eplerenone: 25 mg initially; target dose 50 mg once daily
Spironolactone: 12.5 mg initially; target dose 25 to 50 mg once
daily
 Secondary Prevention Following MI
Lipid-Lowering Agents:
All patients with CAD should receive dietary counseling and
pharmacotherapy in order to reach an LDL cholesterol
concentration <100 mg/dl (and an optional LDL goal of <70
mg/dL) (3).
Statins are the preferred agents for lowering LDL cholesterol and
should be prescribed in most patients (3).
Recent data indicate that all patients with CAD benefit from
statins, regardless of baseline LDL (6). Beyond their lipid-
lowering properties, statins are believed to exhibit pleiotropic
effects, which include plaque stabilization, anti-inflammation,
antithrombotic effects , and modulation of endothelial function
 Secondary Prevention Following MI
Prescribe a short-acting SL NTG or lingual NTG spray for all
patients to relieve angina symptoms when necessary.
Chronic long-acting nitrates have not been shown to reduce CHD
events after MI and are not used in ACS patients who have
undergone revascularization unless the patient has chronic stable
angina or significant coronary stenosis that was not
revascularized.
For all ACS patients, treat and control modifiable risk factors
such as hypertension (HTN), dyslipidemia, obesity, smoking, and
DM
 Secondary Prevention Following MI
TheACC/AHA guidelines recommend warfarin for ACS
patients at high risk for CAD and low bleeding risk who are
unable to take aspirin or clopidogrel, patients with a left
ventricular thrombus, and those with persistent atrial
fibrillation.
The 2007 ACC/AHA guidelines recommend that in patients
receiving warfarin, clopidogrel, and aspirin, an INR of 2.0 to
2.5 is recommended with low-dose aspirin (75 81 mg daily)
and with 75 mg of clopidogrel
Evaluation Of Therapeutic Outcomes
Monitoring parameters for efficacy for both STE and NSTE
ACS include:
1. relief of ischemic discomfort,
2. return of ECG changes to baseline, and
3. absence or resolution of HF signs and symptoms.
Monitoring parameters for adverse effects are dependent on the
individual drugs used.
In general, the most common adverse reactions from ACS
therapies include hypotension and bleeding

 Thank you