Hsm health science

1. ISCHEMIC HEART DISEASE
1

2. INTRODUCTION
Ischemic heart disease (IHD) is also called
coronary heart disease (CHD) or coronary artery
disease (CAD).
“Ischemic” refers to a decreased supply of
oxygenated blood, in this case to the heart muscle
Ischemic heart disease results from an imbalance
between myocardial oxygen supply and oxygen
demand
Angina pectoris, or simply angina, is the most
common
symptom of IHD.
2

3. INTRODUCTION






Common clinical manifestations of IHD include
Chronic stable angina
Acute coronary syndromes (ACS)
Unstable angina (UA)
Myocardial infarction (MI)
Non – ST-segment elevation MI (NSTEMI)
ST-segment elevation MI (STEMI)
Chronic stable angina is defined as a chronic and
predictable occurrence of chest discomfort due to
transient myocardial ischemia with physical exertion
or other conditions that increase oxygen demand.
3

4. 


EPIDEMIOLOGY
Leading cause of death for both men and women in the
US
Incidence of IHD is higher in middle-aged men
compared to women
RISK FACTORS
Non-modifiable
Age ≥45 yrs for males, ≥ 55 yrs for females
Gender (men and postmenopausal women)
Family history of premature cardiovascular disease
cardiovascular disease in their 1st degree relative at
age <55yrs in male or <65 yrs in female
4

5. RISK FACTORS








Modifiable
Cigarette smoking
Dyslipidemia
Elevated LDL or total cholesterol
Reduced HDL cholesterol
Diabetes mellitus
Hypertension
Physical inactivity
Obesity (BMI ≥30 kg/m2) 5

6. PATHOPHYSIOLOGY
Increases in heart rate, left ventricular wall tension,
and cardiac contractility increase the rate of
myocardial oxygen consumption
Left ventricular wall tension is a function of blood
pressure, left ventricular end-diastolic volume, and
ventricular wall thickness.
Physical exertion increases heart rate, blood
pressure, and cardiac contractility, and commonly
precipitates ischemia and symptoms of angina in
patients with significant coronary atherosclerosis
6

7. PATHOPHYSIOLOGY
Reductions in coronary blood flow (secondary to
atherosclerotic plaques, vasospasm, or thrombus
formation) and arterial oxygen content (secondary
to hypoxia) decrease myocardial oxygen supply.
Because the coronary arteries fill during diastole,
decreases in diastolic filling time (e.g., tachycardia)
can also reduce coronary perfusion and myocardial
oxygen supply
In chronic stable angina, atherosclerotic plaques
are the most common cause of coronary artery
narrowing and reductions in coronary blood flow.
7

8. PATHOPHYSIOLOGY
In contrast, in ACS, disruption of an atherosclerotic
plaque with subsequent thrombus (blood clot)
formation causes abrupt reductions in coronary
blood flow and oxygen supply.
Anemia, CO poisoning, and cyanotic congenital
heart disease are examples of conditions that
reduce the oxygen-carrying capacity of the blood,
potentially causing ischemia in the face of
adequate coronary perfusion
8

9. Normal
9

10. Ischemic Heart Disease
10

11. CORONARY ATHEROSCLEROSIS





The normal arterial wall consists of the intima, media,
and adventitia.
The endothelium is located in the intima and consists of
a layer of endothelial cells that line the lumen of the
artery and form a selective barrier between the vessel
wall and blood contents.
The internal elastic lamina separates the intima and
media, where vascular smooth muscle cells are found.
The vascular adventitia comprises the artery’s outer
layer.
Atherosclerotic lesions form in the subendothelial
space between the endothelial cells & internal elastic
lamina.
11

12. 12

13. CORONARY ATHEROSCLEROSIS




Dysfunction of the endothelium allows lipoproteins,
predominantly LDL cholesterol, and inflammatory cells,
namely monocytes and T lymphocytes, to migrate from the
plasma to the sub-endothelial space.
Monocyte-derived macrophages ingest lipoproteins to form
foam cells. Macrophages also secrete growth factors that
promote smooth muscle cell migration from the media to
the intima.
A fatty streak/stripe consists of lipid-loaded macrophages
and smooth muscle cells and is the earliest type of
atherosclerotic lesion.
Lipid-loaded macrophages, smooth muscle cells, and
necrotic
debris from the death of foam cells accumulate in the
subendothelial space, leading to enlargement of the fatty
streak.
13

14. CORONARY ATHEROSCLEROSIS
A collagen matrix forms a fibrous cap that covers the
lipid core of the lesion to establish a fibrous plaque
called an atherosclerotic plaque.
Initially, the diameter of the coronary artery lumen is
maintained as the plaque grows outward (external to the
lumen) in a process referred to as arterial remodeling
However, with significant plaque progression,
atherosclerotic plaque begins to protrude into the artery
lumen and impede blood flow.
When the plaque occludes 70% or more of the artery, the
patient may begin to experience angina during activities
that increase myocardial oxygen demand (i.e., chronic
stable angina) 14

15. STABLE VS UNSTABLE ATHEROSCLEROTIC PLAQUES

The hallmark feature in the pathophysiology of
chronic stable angina is an established
atherosclerotic plaque
that impedes coronary blood flow to the extent
that myocardial oxygen supply can no longer
meet increases in myocardial oxygen demand.
Over time, an established plaque may become
unstable and rupture, leading to an ACS.
Atherosclerotic plaque rupture with subsequent
thrombus formation is the hallmark feature in the
pathophysiology of unstable angina and MI.
15

16. STABLE VS UNSTABLE ATHEROSCLEROTIC PLAQUES
Plaque rupture refers to fissuring or erosion of the
fibrous cap that covers the lipid core and exposure
of the plaque contents to elements in the blood.
Plaque composition, rather than the degree of
coronary stenosis, determines the stability of the
plaque and the likelihood of plaque rupture and ACS.
Specifically, a stable lesion consists of a small lipid
core that is surrounded by a thick fibrous cap that
protects the lesion from the shear stress of blood
flow
16

17. STABLE VS UNSTABLE ATHEROSCLEROTIC
PLAQUES
In contrast, an unstable plaque consists of a thin,
weak cap in combination with a large, rich lipid
core that renders the plaque vulnerable to
rupture
The transformation of a stable plaque into an
unstable plaque involves the degradation of the
fibrous cap by substances released from
macrophages and other inflammatory cells.
An unstable plaque often produces minimal
occlusion of the coronary vessel, and the patient
remains asymptomatic until the plaque ruptures.
17

18. Normal Coronary Artery
Normal coronary artery…….A
In a stable atherosclerotic plaque the lipid core is relatively
small in size and the fibrous cap is made up of several layers
of smooth muscle cells........B
18
Follow the sequences: A-B-C-D-E-F.

19. Unstable atherosclerotic plaque has a larger lipid core, and a
thin fibrous cap comprised of a single layer of smooth muscle
cells with a fissure or rupture…….C
Platelet adhesion in response to the fissured plaque….D
19

20. Platelet activation may ensue leading to platelet aggregation
as fibrinogen binds platelets to one another to form a
meshlike occlusion in the coronary lumen. At this stage,
patients may
experience symptoms of acute coronary syndrome….E
If endogenous anticoagulant proteins fail to halt this
process, platelet aggregation continues and fibrinogen is
converted to fibrin, resulting in an occlusive thrombus….F
20

21. ATHEROSCLEROTIC PLAQUE RUPTURE
Following plaque rupture, exposure of the blood
to the thrombogenic contents of the plaque
stimulates platelet adhesion and activation of
the coagulation cascade.
Platelets adhere to the site of rupture, aggregate,
and generate thrombin
Thrombin converts fibrinogen to fibrin to form a
fibrin clot.
Coronary thrombi extend into the vessel lumen,
where they either partially or completely occlude
blood flow, resulting in unstable angina or MI. 21

22. CORONARY ARTERY VASOSPASM
Prinzmetal’s or variant angina results from spasm (or
contraction) of a normal or diseased coronary artery
In contrast to chronic stable angina, diseased arteries
in variant angina contain lesions that do not obstruct
blood flow
While vasospasm is generally transient, in some
instances vasospasm may persist long enough to
infarct the myocardium
Patients with variant angina are typically younger
than those with chronic stable angina & often do not
possess the classic risk factors for IHD.
22

23. CORONARY ARTERY VASOSPASM
Variant angina usually occurs at rest,
especially in the early morning hours.
The cause of variant angina is unclear but
appears to involve endothelial dysfunction and
paradoxical response to agents that normally
cause vasodilation
Precipitants of variant angina include cigarette
smoking, cocaine use, hyperventilation, and
exposure to cold temperatures
23

24. CLINICAL PRESENTATION AND DIAGNOSIS
Symptoms of Angina Pectoris
Patients typically describe pain as a sensation
of pressure, heaviness, or squeezing in the
anterior chest area. Sharp pain is not a typical
symptom of IHD.
Pain may radiate to the neck, jaw, shoulder,
back, or arm.
Pain may be accompanied by dyspnea,
nausea, vomiting, or diaphoresis
24

25. CLINICAL PRESENTATION AND DIAGNOSIS
Symptoms are often provoked by exertion (e.
g., walking, climbing stairs, and doing yard or
house work) or emotional stress and relieved
within minutes by rest or nitroglycerin.
Other precipitating factors include exposure
to cold temperatures and heavy meals.
Pain that occurs at rest (without provocation)
or that is prolonged and unrelieved by
nitroglycerin is indicative of an ACS. 25

26. CLINICAL PRESENTATION AND DIAGNOSIS
1.


Laboratory Tests
Biochemical markers (creatine kinase [CK],
CK-MB fraction, troponin I and troponin T):
Elevated in MI (ST-segment elevation MI
and non–ST-segment elevation MI)
Normal in chronic stable angina and
unstable angina.
26

27. CLINICAL PRESENTATION AND DIAGNOSIS
2.



3.
ECG
Normal at rest in patients with chronic stable
angina in the absence of active ischemia
Significant Q waves indicate prior MI.
ST-segment depression or T-wave inversion is
typically observed in chronic stable angina,
unstable angina, and non–STEMI, whereas ST-
segment elevation occurs with STEMI and
Prinzmetal’s (variant) angina
Coronary Angiography: detects the location and
degree of coronary atherosclerosis
27

28. Ischemic chest discomfort symptoms, lasting at least 20
minutes;
Suspect acute coronary syndrome
ECG
ST-segment elevation No ST-segment
elevation
STEM
I
Troponin & CK MB
“Negative” Positive
UA NSTE
ST-segment depression
T-wave inversion
28
UA ... unstable angina

29. ST-segment
elevation
ST-segment
depression
T-wave inversion No ECG changes
29

30. THE CANADIAN CARDIOVASCULAR SOCIETY
CLASSIFICATION SYSTEM OF ANGINA
I.
II.
III.
IV.
Class I to IV.
Able to perform ordinary physical activity (e.g.,
walking and climbing stairs) without symptoms.
Strenuous, rapid, or prolonged exertion causes
symptoms.
Symptoms slightly limit ordinary physical activity.
Walking rapidly or for more than two blocks,
climbing stairs rapidly or climbing more than one
flight of stairs causes symptoms.
Symptoms markedly limit ordinary physical activity.
Walking less than two blocks or climbing one flight
of stairs causes symptoms.
Angina may occur at rest. Any physical activity
30

31. DISTINGUISHING CHARACTERISTICS OF
CHRONIC STABLE ANGINA AND UNSTABLE
ANGINA





Chronic Stable Angina:
Is due to increases in oxygen demand, not acute
changes in oxygen supply
Usually occurs with exertion
Symptoms are typically reproducible and
reversible.
Patients will generally experience a similar pattern
of discomfort (same quality, location, and
accompanying symptoms) with a similar level of
exertion with each angina attack
Is usually relieved within minutes by rest or
sublingual nitroglycerin
31

32. DISTINGUISHING CHARACTERISTICS OF CHRONIC
STABLE ANGINA AND UNSTABLE ANGINA





Unstable Angina:
it is associated with a greater risk for MI & death than
stable angina and requires more aggressive
treatment
Is due to an acute decrease in coronary blood flow
leading to insufficient oxygen supply.
Marked by prolonged symptoms (greater than or
equal to 20 minutes) or an escalation in the frequency
or severity of angina over a short period of time
frequently occurs at rest without any precipitating
factors,
May be less responsive to rest or medication. 32

33. MANAGEMENT




Desired Outcomes, Stable angina
Prevent acute coronary syndromes and death
Alleviate acute symptoms of myocardial
ischemia
Prevent recurrent symptoms of myocardial
ischemia
Avoid or minimize adverse treatment effects.
33

34. (1)
(2)
(3)
(4)



Desired Outcomes, ACS
Short-term desired outcomes
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)
Prevention of death and other complications
Prevention of coronary artery reocclusion
Relief of ischemic chest discomfort
Long-term desired outcomes
Control of risk factors,
Prevention of additional cardiovascular events, and
Improvement in quality of life
34
MANAGEMENT

35. MANAGEMENT OF STABLE ANGINA




GENERAL APPROACH TO TREATMENT
Modify cardiovascular risk factors;
Slow the progression of coronary atherosclerosis;
Stabilize existing atherosclerotic plaques.
LIFESTYLE MODIFICATIONS
Smoking cessation
Dietary modifications
Increased physical activity, and
Weight loss
35

36. GENERAL APPROACH TO
TREATMENT


Control of Risk Factors
Dyslipidemia: LDL cholesterol goal is <100 mg/dL for
patients with documented IHD or IHD risk equivalents
such as diabetes or other vascular disease
Statins are the preferred drugs to achieve this goal
Hypertension: Goal BP in patients with IHD is <140/90
mmHg
β-blockers & ACEIs/ARBs , either alone or in
combination, are appropriate for most patients with
both hypertension and IHD.
Pharmacotherapy
Pharmacotherapy to Prevent ACS and Death
Pharmacotherapy to Relieve Acute Symptoms
Prevention of Recurrent Ischemic Symptoms
36
STABLE ANGINA

37. PHARMACOTHERAPY TO PREVENT ACS AND
DEATH
1.




Antiplatelet Agents
Thromboxane is a potent platelet activator.
Aspirin inhibits cyclooxygenase, an enzyme
responsible for the production of thromboxane.
Antiplatelet therapy with aspirin should be
considered for all patients without
contraindications, particularly in patients with a
history of myocardial infarction.
Aspirin doses of 75 to 325 mg daily have been
shown to be cardioprotective. 37
STABLE ANGINA

38. PHARMACOTHERAPY TO PREVENT ACS AND DEATH



If aspirin is contraindicated;
aspirin allergy,
active peptic ulcer disease, or
active internal bleeding or is not tolerated by the
patient,
Alternative antiplatelet agents: e.g. clopidogrel
Combination antiplatelet therapy (aspirin and
clopidogrel): may be synergistic in reducing the risk
of IHD-related events.
38
STABLE ANGINA

39. PHARMACOTHERAPY TO PREVENT ACS AND DEATH
2.



Statins
Statins are generally considered the drugs
of choice in patients with dyslipidemias.
have been shown to reduce morbidity and
mortality in patients with IHD
Statins should be considered in all patients
with IHD at high risk of major adverse
cardiac events, regardless of baseline LDL
cholesterol 39
STABLE ANGINA

40. PHARMACOTHERAPY TO PREVENT ACS AND DEATH
3.



ACEIs and ARBs
In the absence of contraindications, ACEIs
should be considered in IHD patients who also
have DM, left ventricular dysfunction, history of
MI, or any combination of these.
In addition, they should also be considered in all
patients with IHD and in patients at high risk for
developing IHD
ARBs may be used in patients who cannot
tolerate ACEIs due to side effects (e.g., chronic
cough)
40
STABLE ANGINA

41. PHARMACOTHERAPY TO RELIEVE ACUTE
SYMPTOMS
Nitrates
Short-acting nitrates are first-line treatment to
terminate acute episodes of angina.
All patients with a history of angina should
have sublingual nitroglycerin tablets or spray
to relieve acute ischemic symptoms
Nitrates undergo biotransformation to nitric
oxide.
Nitric oxide results smooth muscle relaxation.
41
STABLE ANGINA

42. 
Nitrates primarily cause venodilation, leading to
reductions in preload.
The resultant decrease in ventricular volume and
wall tension leads to a reduction in myocardial
oxygen demand.
Nitrates increase myocardial oxygen supply by
dilating the epicardial coronary arteries and
collateral vessels, as well as relieving vasospasm.
Short-acting nitrates are available in tablet and spray
formulations for sublingual administration 42
PHARMACOTHERAPY TO RELIEVE ACUTE
SYMPTOMS
STABLE ANGINA

43. PHARMACOTHERAPY TO RELIEVE ACUTE
SYMPTOMS

At the onset of an angina attack, a 0.3 to 0.4 mg dose
of nitroglycerin (tablet or spray) should be
administered sublingually, and repeated every 5
minutes until symptoms resolve.
Sublingual nitroglycerin can also be used to prevent
effort-induced angina.
The patient should use sublingual nitroglycerin 2 to
5 minutes prior to an activity known to cause
angina, with the effects persisting for
approximately 30 minutes.
Nitroglycerin should not be used within 24 hours of
taking sildenafil or vardenafil or within 48 hours of
43
STABLE ANGINA

44. PHARMACOTHERAPY TO RELIEVE ACUTE
SYMPTOMS
Isosorbide dinitrate, also available in a sublingual
form, has a longer half-life with anti-anginal effects
lasting up to 2 hours.
The use of short-acting nitrates alone, without
concomitant long-acting anti-anginal therapy, may
be acceptable for patients who experience angina
symptoms once every few days.
However, for patients with more frequent attacks,
long-acting anti-anginal therapy with β-blockers,
calcium channel blockers, or long-acting nitrates is
recommended. 44
STABLE ANGINA

45. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
1. Beta-Blockers
β-Blockers decrease myocardial oxygen demand
by decreasing heart rate, cardiac contractility, blood
pressure and ventricular wall tension
β-Blockers are contraindicated in patients with
severe bradycardia (heart rate less than 50 beats
per minute)
Other contraindications include asthma,
bronchospastic disease, severe depression, and
peripheral vascular disease 45
STABLE ANGINA

46. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
2. Calcium Channel Blockers (CCBs)
Inhibit calcium entry into the vascular smooth muscle
cells systemic vasodilation and reductions in afterload.
Inhibit calcium entry into the cardiac cells reductions in
cardiac contractility   myocardial oxygen demand
The nondihydropyridine CCBs (verapamil and diltiazem)
slow cardiac conduction through the AV nodes and
lowering heart rate myocardial oxygen demand
In contrast, dihydropyridine CCBs, nifedipine in particular,
are potent vasodilators that can cause baroreflex-
mediated increases in sympathetic tone and heart rate.
46
STABLE ANGINA

47. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
2. CCBs
Because of their negative chronotropic effects, verapamil
and diltiazem are generally more effective anti-anginal agents
than the dihydropyridine CCBs.
All CCBs increase myocardial oxygen supply by dilating
coronary arteries, thus increasing coronary blood flow and
relieving vasospasm.
Calcium channel blockers are recommended as initial
treatment in IHD when -blockers are contraindicated or not
tolerated.
CCBs may be used in combination with -blockers when initial
treatment is unsuccessful.
47
STABLE ANGINA

48. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
2. CCBs
However, the combination of a β-blocker with either
verapamil or diltiazem should be used with extreme
caution since all of these drugs decrease AV nodal
conduction, increasing the risk for severe bradycardia
or AV block when used together
β-Blockers will prevent reflex increases in
sympathetic tone and heart rate with the use of
calcium channel blockers with potent vasodilatory
effects.
48
STABLE ANGINA

49. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
3. Long-Acting Nitrates
Nitrate products are available in both oral and
transdermal formulations for chronic use.
•





•

Oral
Nitroglycerin extended-release capsules
Isosorbide dinitrate tablets
Isosorbide dinitrate slow-release capsules
Isosorbide mononitrate tablets
Isosorbide mononitrate extended-release
tablets
Transdermal
Nitroglycerin extended-release film
49
STABLE ANGINA

50. NITRATE FORMULATIONS AND DOSING FOR CHRONIC USE
Formulation Dose nitrate-free
interval
Nitroglycerin XR 2.5 mg TID 10 – 12-hour
Isosorbide dinitrate 5–20 mg BID to
TID
At least 14 hours
Isosorbide dinitrate
slow release
40 mg QD to BID at least 18 hours
Isosorbide
mononitrate
5–20 mg BID taken 7 hours
apart
Isosorbide
mononitrate
XR
30–120 mg QD
Nitroglycerin XR film 0.2–0.8 mg/hour, on for 12–14 hours,
off for 10–12
50
STABLE ANGINA

51. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
3. Long-Acting Nitrates
The major limitation of nitrate therapy is the
development of tolerance with continuous use.
The loss of anti-anginal effects may occur within the
first 24 hours of continuous nitrate therapy
The most effective method to avoid tolerance and
maintain the anti-anginal efficacy of nitrates is to
allow a daily nitrate-free interval of at least 8 to12
hours
Nitrates do not provide protection from ischemia
during the nitrate-free period.
51
STABLE ANGINA

52. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
3. Long-Acting Nitrates
Therefore, the nitrate-free interval should occur
when the patient is least likely to experience angina.
Generally, angina is less common during the
nighttime hours when the patient is sleeping and
myocardial oxygen demand is reduced.
Thus, it is common to dose long-acting nitrates so
that the nitrate-free interval begins in the evening.
52
STABLE ANGINA

53. PREVENTION OF RECURRENT ISCHEMIC SYMPTOMS
3. Long-Acting Nitrates
Treatment with long-acting nitrates should be added
to baseline therapy with either a β-blocker or calcium
channel blocker or a combination of the two.
β-Blockers attenuate the increase in sympathetic
tone and heart rate that occurs during nitrate therapy.
Common adverse effects of nitrates include postural
hypotension, flushing, and headache secondary to
venodilation.
53
STABLE ANGINA

54. NON-PHARMACOLOGIC THERAPY


Primary Percutaneous Coronary Intervention for STE
ACS
Early reperfusion therapy with either primary
percutaneous coronary intervention or
administration of a fibrinolytic agent within 3 hours
of symptom onset is the recommended therapy for
patients presenting with STE ACS
More than 90% of occluded infarct-related coronary arteries are
opened with primary PCI compared to fewer than 60% of
coronary arteries opened with currently available fibrinolytics
Comparing fibrinolysis to primary PCI indicate a
lower mortality rate with primary PCI
Intracranial hemorrhage and major bleeding risks from
primary PCI are lower than the risks of severe bleeding
events following fibrinolysis.
54
MANAGEMENT OF ACS
AC
S

55. 







Percutaneous Coronary Intervention (PCI)
Recommended with >1 vessel coronary occlusion
commonly known as coronary angioplasty or simply
angioplasty
is a therapeutic procedure to treat the stenotic (narrowed)
coronary arteries
PCI is usually performed by an interventional cardiologist
Angioplasty is less invasive than CABG
Sometimes referred to as balloon angioplasty which
describes the inflation of a balloon within the coronary
artery to crush the plaque into the walls of the artery
Other procedures done during a PCI include; implantation
of stents, rotational or laser athrectomy
Stents are rings placed in the vessel to keep vessel
open/ not to reocclude after angioplasty
Should be performed as quickly as possible
55

56. NON-PHARMACOLOGIC THERAPY





Coronary Artery Bypass Graft (CABG)
Emergency or urgent CABG occurs with failed PCI,
persistent pain or hemodynamic instability, persistent
ischemia refractory to medical therapy, pts with severe
multivessel disease, pts who are not candidates for PCI/
fibrinolytic therapy
Also called heart bypass or bypass surgery
Surgical procedure performed to relieve angina and reduce
the risk of death from CAD
Arteries or veins from elsewhere in the patients body are
grafted to the coronary arteries to bypass atherosclerotic
narrowing and improve the blood supply to the heart
The terms single bypass, double bypass, triple bypass,
quadruple bypass and quintuple bypass refer to the
number of coronary arteries bypassed in the procedure
56

57. PHARMACOTHERAPY
1. Early Pharmacologic Therapy for STE ACS
In addition to reperfusion therapy, early
pharmacotherapy of STE should include:
Intranasal oxygen,
SL NTG (sublingual nitroglycerin)
Followed by
IV NTG
Aspirin
IV -blocker
Unfractionated heparin (UFH)
Fibrinolysis
57
AC
S

58. 1. EARLY PHARMACOTHERAPY FOR STE
ACS
Clopidogrel should be administered along with
aspirin to patients receiving fibrinolytics to reduce
mortality and reinfarction as well as to improve the
patency of the infarcted artery.
Morphine is administered to patients with refractory
angina as an analgesic
58
AC
S

59. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS


Fibrinolytic Therapy: Streptokinase, alteplase,
reteplase, or tenecteplase
Administration of a fibrinolytic agent is indicated
in patients with STE ACS who present to the
hospital within 24 hours of the onset of chest
discomfort
Fibrinolytic therapy is preferred over primary PCI
in patients presenting within 3 hours of symptom
onset
59
AC
S

60. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS
Patients who are at high-risk of major bleeding
(including intracranial hemorrhage) have either a
relative or absolute contraindication to fibrinolytic
therapy.
Patients presenting with an absolute contraindication
will likely not receive fibrinolytic therapy, as primary
PCI is preferred.
Patients with a relative contraindication may receive
fibrinolytic therapy if the perceived risk of death from
the MI is higher than the risk of major hemorrhage
60
AC
S

61. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS






Absolute Contraindications to fibrinolytic therapy
Active internal bleeding (not including menses)
Previous intracranial hemorrhage at any time;
ischemic stroke within 3 months
Known intracranial neoplasm
Known structural vascular lesion (e.g.,
arteriovenous malformation)
Suspected aortic dissection
Significant closed head or facial trauma within
3 months
61
AC
S

62. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS








Relative Contraindications to fibrinolytic therapy
Severe, uncontrolled hypertension on presentation
(blood pressure greater than 180/110 mm Hg)
History of prior ischemic stroke greater than 3
months ago, dementia, or known intracranial
pathology not covered above under absolute
contraindications
Current use of anticoagulants
Known bleeding diathesis
Traumatic or prolonged (greater than 10 minutes)
CPR or major surgery (less than 3 weeks ago)
Pregnancy
Active peptic ulcer
Recent (within 2–4 weeks) internal bleeding
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63. 1. EARLY PHARMACOLOGIC THERAPY FOR STE ACS


Aspirin
The antiplatelet effects of aspirin are mediated by
inhibiting the synthesis of TXA2 through an
irreversible inhibition of platelet
cyclooxygenase-1
Aspirin should be administered to all patients who
don’t have contraindications to it within the first
24 hours of hospital admission
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64. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS
In patients undergoing PCI, aspirin prevents acute
thrombotic occlusion during the procedure.
In patients receiving fibrinolytics, aspirin reduces
mortality, and its effects are additive to fibrinolysis
alone
Initial dose of 160 to 325 mg is required to achieve
rapid platelet inhibition
Daily maintenance dose of 75 to160 mg is
recommended
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65. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS






Thienopyridines
Clopidogrel blocks ADP receptors on platelets,
preventing the expression of glycoprotein IIb/IIIa
receptors and thus platelet activation and
aggregation.
Administration of clopidogrel is recommended for all
patients with STE ACS
Clopidogrel reduces death, MI, or stroke in patients
with NSTE ACS when combined with aspirin.
Clopidogrel 75 mg once daily
The most frequent side effect of clopidogrel is rash or
gastrointestinal events (NVD)
The most serious side effect of clopidogrel is
bleeding
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66. 1. EARLY PHARMACOLOGIC THERAPY FOR STE ACS



Anticoagulants
Unfractionated heparin, administered as a
continuous infusion, is a first-line anticoagulant for
treatment of patients with STE ACS, both for
medical therapy and for patients undergoing PCI
Unfractionated heparin binds to antithrombin and
then to clotting factors Xa and IIa (thrombin).
Anticoagulant therapy should be initiated in the
emergency department and continued for 48 hours
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67. 1. EARLY PHARMACOLOGIC THERAPY FOR STE ACS


Nitrates
One sublingual nitroglycerin tablet should be
administered every 5 minutes for up to three
doses in order to relieve myocardial ischemia.
Nitrates promote the release of nitric oxide from
the endothelium, which results in venous and
arterial vasodilation
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68. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS




Beta-Blockers
Intravenous or oral doses of a β-blocker should be
administered early in the care of a patient with STE ACS,
and then oral agents should be continued indefinitely.
β-blockers should be administered to patients lacking a
contraindication within the first 24 hours of
hospitalization
β1-Blockade produces a reduction in heart rate,
myocardial contractility, and blood pressure, decreasing
myocardial oxygen demand.
β-blockers reduce the risk for recurrent ischemia,
increase in infarct size and risk of reinfarction, and
occurrence of ventricular arrhythmias in the hours &
days following MI
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69. 1. EARLY PHARMACOLOGIC THERAPY FOR STE
ACS



Calcium Channel Blockers
CCBs in the setting of STE ACS are used for relief
of ischemic symptoms in patients who have
contraindications to β-blockers
Dihydropyridine CCBs (e.g., amlodipine,
felodipine, and nifedipine) produce their anti-
ischemic effects through peripheral
vasodilatation with no clinical effects on AV node
conduction and heart rate.
The nondihydropyridine CCBs (e.g., diltiazem and
verapamil), have additional anti-ischemic effects
by reducing contractility, AV nodal conduction, &
slowing HR
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70. 2. EARLY PHARMACOTHERAPY FOR NSTE
ACS






In the absence of contraindications , early
pharmacotherapy of NSTE ACS should include:
Intranasal oxygen
SL NTG
Followed by:
IV NTG
Aspirin
IV -blocker and
UFH or LMWH.
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71. 2. EARLY PHARMACOTHERAPY FOR
NSTE ACS

Most patients should receive additional therapy
with clopidogrel.
Morphine is also administered to patients with
refractory angina
Fibrinolytic therapy is not indicated in any patient
with NSTE ACS
Since increased mortality has been reported with
fibrinolytics compared to controls in clinical trials in
which fibrinolytics have been administered to patients
with NSTE ACS (patients with normal or ST-segment
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72. 3. SECONDARY PREVENTION FOLLOWING MI
(1)
(2)
(3)
(4)
The long-term goals following MI are to:
Control modifiable CHD risk-factors,
Prevent the development of systolic heart failure,
Prevent recurrent MI and stroke, and
Prevent death, including sudden cardiac death.
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73. 3. SECONDARY PREVENTION FOLLOWING MI



In the absence of contraindications, following MI
from either STE ACS or NSTE ACS, patients should
receive indefinite treatment with
Aspirin
-blocker, and
ACE inhibitor
For NSTE ACS, most patients should receive
clopidogrel, in addition to aspirin, for up to 9
months.
Most patients will receive a statin to reduce LDL
cholesterol to less than 100 mg/dL.
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74. 3. SECONDARY PREVENTION FOLLOWING MI
Selected patients will also be treated with long term
warfarin anticoagulation.
Newer therapies include eplerenone, an aldosterone
antagonist.
For all ACS patients, treatment and control of
modifiable risk factors such as hypertension,
dyslipidemia, and diabetes mellitus is essential
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