This document discusses stable and acute ischemic heart disease. It begins by defining coronary heart disease and coronary artery disease. It then discusses the etiology, pathophysiology, risk factors, classification, clinical presentation, and desired outcomes of stable ischemic heart disease. It covers the general treatment approach including risk factor modification, drug therapy using antiplatelet agents, ACE inhibitors, statins, beta-blockers, calcium channel blockers, and nitrates. It then discusses acute coronary syndromes including unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction. It covers risk stratification, general treatment approach, and early pharmacotherapy for ST-elevation myocardial infarction.

1. Stable and acute Ischemic
Heart Disease
Gobezie T
§CHD §1

2. Introduction
 Coronary heart disease (CHD) is the most common
type of heart disease and cause of heart attacks.
 also known as atherosclerotic heart disease,
 coronary artery disease (CAD), or
 ischemic heart disease (IHD)
 Coronary artery disease is the narrowing or blockage
of the coronary arteries,
 usually caused by atherosclerosis.
2

3. ETIOLOGY
Angina pectoris.
 Coronary atherosclerosis.
 Coronary artery spasm.
 Coronary artery embolism or thrombosis.
 This can cause chest pain called angina.
3

4. 4

5. 5

6. PATHOPHYSIOLOGY….(2)
 Progressive decrease in vessel radius associated with
 coronary atherosclerosis impairs coronary blood flow
and causes angina pectoris
 when myocardial oxygen demand ↑s, as with exertion.
 Angina pectoris may occur because of
 abrupt reduction in blood flow due to
• coronary thrombosis (unstable angina) or localized
vasospasm (variant or Prinzmetal angina)
• without increased oxygen demand.
6

7. Risk factors
Non-modifiable risk factors (those that cannot be
changed) include:
 Male gender.
 Advanced age.
 Family history of heart disease
7

8. Risk factors…
Modifiable risk factors (you can treat or control) include:
 Cigarette smoking and exposure to tobacco smoke
 High blood cholesterol and high triglycerides
 HTN (130/80 mm/Hg or higher)
 Uncontrolled diabetes
 Physical inactivity
 Being overweight (BMI 25-29 or being obese (BMI >30
kg/m2)
 Uncontrolled stress or anger
 Diet high in saturated fat and cholesterol 8

9. Classification
 IHD
 Stable angina
 Acute coronary syndrome
• Unstable angina
• non ST elevation MI
• ST elevation MI
9

10. Grading of Angina Pectoris by the Canadian
Cardiovascular Society Classification System
Class Description of Stage
Class I Ordinary physical activity does not cause angina, such as walking,
climbing stairs. Angina occurs with strenuous, rapid, or prolonged
exertion at work or recreation.
Class II Slight limitation or ordinary activity. Angina occurs on walking or
climbing stairs rapidly, walking uphill, walking or stair climbing after
meals, or in cold, or in wind, or under emotional stress, or only
during the few hours after wakening. Walking more than 2 blocks
on the level and climbing more than 1 flight of ordinary stairs at a
normal pace and in normal condition.
Class III Marked limitations of ordinary physical activity. Angina occurs on
walking 1 to 2 blocks on the level and climbing 1 flight of stairs in
normal conditions and at a normal pace.
Class IV Inability to carry on any physical activity without discomfort—
anginal symptoms may be present at rest.
10

11. Clinical Presentation
 Symptoms
 sensation of pressure/burning
over or near sternum; often but
not always radiating
• left jaw, shoulder, arm
 chest tightness, shortness of
breath
 visceral pain: lasts 0.5 to 30 min
 precipitating factors: exercise,
cold environment, walking after a
meal, emotional upset, fright,
anger, coitus
 relief with rest, nitroglycerin
11
 Signs
 abnormal precordial
systolic bulge
 abnormal heart sounds
 Typically no abnormal
laboratory tests
 Likely to have abnormal
tests for IHD risk factors
 History of chest pain

12. 12

13. Desired Outcomes
Alleviate acute symptoms of myocardial ischemia
 Reduce the number of ischemic episodes as well
as
 increasing the amount of exertion or exercise a
patient can accomplish before inducing an
ischemic episode.
 Slow the progression of atherosclerosis and
 preventing complications of such as MI, HF,
stroke, & death.
Avoid or minimize adverse treatment effects.
13

14. General Treatment
 Identification & treatment of aggravating
conditions
 Anemia
 Thyrotoxicosis
 Aortic valve diseases
 Obesity
 Prevention & control of HTN, dyslipidemia, and
DM.
 Avoidance of drugs that may be detrimental.
14

15. Treatment
General Approach to Treatment
The primary strategies for preventing ACS and death
are to:
 Modify cardiovascular risk factors;
 Slow the progression of coronary atherosclerosis;
and
 Stabilize existing atherosclerotic plaques.
 Non-pharmacologic therapy
15

16. Non-pharmacologic therapy
 Surgical revascularization plays an important role in
the treatment of SIHD.
 The most common revascularization procedures are
coronary artery bypass grafting (CABG) surgery or
percutaneous coronary intervention (PCI) with or
without stent placement
16

17. 17

18. Drug therapy
 Treatment Improve mortality in patients with SIHD by
providing guideline-directed medical therapy
(GDMT).
 Anti-platelet agents
 ACE inhibitors/ARBs
 Statins
 B-blockers
 Calcium channel blockers
 Nitrates
18

19. Antiplatelet Agents
 platelets adhere to the site of atherosclerotic plaque rupture
activated,
Aggregated
stimulate thrombus formation and ACS.
o Guideline recommendations:
 Aspirin 75–162 mg daily for all pnts, continued indefinitely in
the absence of contraindications, particularly in patients with
a Hx of MI.
 Clopidogrel is a reasonable when aspirin is contraindicated.
 Tt with aspirin (75–162 mg/d) and clopidogrel 75 mg/d might
be reasonable in certain high-risk patients with SIHD.
19

20. ACE Inhibitors
 ACEIs have demonstrated the ability to:
 stabilize coronary plaque,
 provide restoration or improvement in endothelial
function,
 inhibition of vascular smooth muscle cell growth,
 ↓ed macrophage migration, and
 possibly possess some antioxidant activities.
20

21. Risk factor modification.
Lipid management: Statins
 Guidelines recommend
 All patients with known atherosclerotic CVD, such as SIHD,
should receive high-intensity statin therapy. High-intensity
statin options:
• Atorvastatin 40 or 80 mg (preferred dose) daily.
• Rosuvastatin 20 (preferred dose) or 40 mg daily.
 Patients over the age of 75 years, or those who cannot
tolerate high-intensity statin, should receive moderate-
intensity statin.
• Moderate-intensity statin options:
• Atorvastatin 10–20 mg, Rosuvastatin 5–10 mg.
• Simvastatin 20–40 mg, Pravastatin 40 mg, Lovastatin 40
mg.
21

22. Risk factor modification….
 Blood pressure management.
 Drug selection in SIHD includes agents typically used to treat
other aspects of the disease.
• βBs, ACEIs & CCBs can be added if additional
therapy needed.
• Thiazide diuretics could also be an option.
 Smoking cessation.
 Nicotine replacement therapy.
 Sustained release bupropion.
22

23. Treatment for Symptom relief.
 βBs: Effective in reducing both symptomatic and silent
episodes of myocardial ischemia.
 CCBs: Effective at reducing angina episodes, Reduction in
MVO2
 Can be used safely in many patients with CIs to βB therapy.
 Short-acting nitrates: First-line for acute attacks. NG SL 2–5
min prior to activities prevent predicted attacks.
 Long-acting nitrates: Use is limited to tolerance.
 Ranolazine.
 Option for patients who cannot tolerate any of the traditional
agents due to hemodynamic or other adverse effects. 23

24. Short-acting nitrates.
Nitroglycerin to Relieve Acute Symptoms
 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
 primarily cause venodilation reductions in preload
 decrease in ventricular volume and wall tension
 reduction in myocardial oxygen demand.
 At higher doses, nitrates may also cause arterial dilation &
24

25. Long-Acting Nitrates (LANs)
 Isosorbide dinitrate, in a sublingual form, has a longer half-
life with anti-anginal effects lasting up to 2 hours.
 for patients with more frequent attacks, LANs is
recommended.
 The major limitation of nitrate therapy is the development of
tolerance with continuous use.
 Provide nitrate-free interval of 10–14 hrs per day or longer to
maintain efficacy.
25

26. Beta-Blockers
 Stimulation of the β1-and β2- receptors in heart ↑ HR and
cardiac contractility.
 βBs ↓ myocardial oxygen demand by
Antagonizing β1-and β2- Stimulation
Lowering BP and ventricular wall tension.
 βBs may ↑ ventricular wall tension.
 However, the net effect of β-blockade is usually a reduction in
myocardial oxygen demand
 βBs with intrinsic sympathomimetic activity
produce lesser reductions in myocardial oxygen demand
and should be avoided in patients with IHD.
 Other βBs appear equally effective at controlling symptoms of
26

27. Calcium Channel Blockers
 Inhibition of calcium entry into the vascular smooth muscle
cells leads to systemic vasodilation and reductions in
afterload.
 Inhibition of calcium entry into the cardiac cells leads to
reductions in cardiac contractility.
Reduction in wall tension
Reduction in myocardial oxygen demand
 Nondihydropyridine CCBs further ↓ myocardial oxygen
demand.
 Due to their negative chronotropic effects, verapamil &
diltiazem are generally more effective anti-anginal agents than
dihydropyridine CCBs.
27

28. Calcium Channel Blockers
 CCBs are recommended as initial treatment in IHD when
βBs are contraindicated or not tolerated.
 In addition, CCBs may be used in combination with βBs
when initial treatment is unsuccessful.
A long-acting dihydropyridine CCB is preferred.
Amlodipine and felodipine possess less negative inotropic
effects and appear to be safe in left ventricular systolic
dysfunction.
 Finally, there is some evidence that short acting CCBs
(particularly short acting nifedipine & nicardipine) may ↑
risk of CV events. 28

29. Treatment: Special Considerations
 Variable threshold angina and Prinzmetal’s
angina.
 Nitrates & CCBs are effective agents for reducing
vasospasm.
 Most patients respond well to SL NTG for acute
attacks.
Nifedipine, verapamil, & diltiazem are all equally
effective as single agents for initial management
of coronary vasospasm.
Dose titration is important to maximize the
29

30. Acute Coronary Syndromes
30

31. Acute coronary syndromes
 Unstable angina (UA)
 Myocardial infarction (MI): Non-ST-Segment Elevation
MI (NSTEMI & UA), ST-Segment Elevation MI
(STEMI)
 The cause of an acute coronary syndrome is
 the rupture of an atherosclerotic plaque with
subsequent platelet adherence, activation, and
aggregation, and the activation of the clotting
cascade.
• Ultimately, a clot forms composed of fibrin and
platelets. 31

32. 32

33. 33

34.  Unstable angina
 Angina with at least one of the three features
• It occurs at rest, lasts >10 min
• Severe & of new onset, with in the past 4-6 wks.
 NSTEMI
 UA + elevated cardiac biomarkers
 STEMI: NSTEMI + ST elevaiton
30 day mortality rate is 30 %, ½ of it occurs
before the patient reaches the hospital
34

35. Risk Stratification
35
 TIMI Risk Score for NSTE-ACS
 Risk of death, MI, or urgent need for revascularization as
follows: (One point for each of seven)
 Age >65 years
 >3 CHD risk factors: (smoking, hypercholesterolemia, HTN,
DM, Fx of premature CHD death/events)
 Known CAD (50% or greater stenosis of at least one major
coronary artery on coronary angiogram)
 Aspirin use within the past 7 days
 Two or more episodes of chest discomfort within past 24
hours
 ST-segment depression 0.5 mm or greater
 Positive biochemical marker for infarction
 TIMI Risk Score (5-7 points= High, 3-4 =Medium, 0-2= Low-

36. Acute Coronary Syndromes:
Treatment
DESIRED OUTCOMES
The short-term goals of Rx for ACS patient are as
follows:
 Early restoration of blood flow to the infarct-related
artery to prevent infarct expansion (in case of MI) or
prevent complete occlusion and MI (in unstable
angina)
 Prevention of death and other complications
 Prevention of coronary artery reocclusion
 Relief of ischemic chest discomfort
 resolution of ST-segment and T-wave changes on the
ECG.
Long-term desired outcomes are
 control of CV risk factors,
36

37. General approach….
 STEMI,
• immediate primary PCI with balloon angioplasty or
stent placement is reperfusion treatment of choice
when patient presents within 12 hours of symptom
onset.
 NSTE ACS at low risk:
 Obtain serial biochemical markers.
 High-risk NSTE ACS:
 early coronary angiography (within 24 hours) &
revascularization if significant stenosis is found.
37

38. Early Pharmacotherapy for STE ACS
 In Emergency department (ED):
 Morphine PRN
 Oxygen (if SO2<90)
 sublingual ± IV NTG
 DAT: (ASA+P2Y12Is)
 Anticoagulant (UFH or enoxaparin/fondaparinux/
bivalirudin)
 β-blocker (in ED, within first 24 h)
 Fibrinolysis
38

39. Tt Algorism for STE MI
39

40. Fibrinolytic Therapy
Administer within 30 min of arrival of STE ACS
patients if
 Presenting to hospital within 12 hours of onset of chest
discomfort
 and have at least 1 mm of STE .
Also consider in STE ACS 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.
40

41. Thrombolytics
Drug Fibrin
Specificity
Dose
Streptokinase (SK)
(Streptase)
+ 1.5 MU in 50 mls NS/D5W IV over 60 mins
Tissue plasminogen
activator (tPA)
(Alteplase)
+++ IV Bolus: 15 mg, 0.75 mg/Kg over 30 mins
(max: 50mg), 0.5mg/Kg over 1 hr (max 35mg)
(max dose 100 mg)
Reteplase (rPA)
(Retevase)
++ 10 U IV push over 2 min, repeat after 30 min
Tenecteplase (TNK)
(TNKase)
++++ Single IV bolus given over 5 s based on weight
< 60Kg: 30 mg IV Bolus
60-70Kg: 35 mg IV Bolus
71-80Kg: 40 mg IV Bolus
81-90Kg: 45mg IV Bolus
> 91Kg: 50mg IV Bolus
41
alteplase, reteplase, & tenecteplase are acceptable as first-line agents.

42. Aspirin
Early aspirin administration to all patients without
contraindications within the first 24 hours of hospital
admission
In patients undergoing PCI, aspirin prevents acute
thrombotic occlusion during the procedure.
In patients experiencing ACS, an initial dose ≥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.
42

43. Thienopyridines.
 Should be used as soon as possible concomitantly
with aspirin to prevent subacute stent thrombosis
and longer term CV events.
 Recommended duration is 12 months following
PCI for STEMI receiving a bare metal stent or
drug-eluting stent.
 Clopidogrel
43

44. Glycoprotein (GP) IIb/IIIa receptor
inhibitors.
 Do not give GPIs to STEMI patients who will not undergo
PCI.
 If UFH is selected for primary PCI in STEMI, add GPIs
 to UFH (in addition to a thienopyridine and aspirin)
 to reduce likelihood of reinfarction for patients not given
fibrinolytics.
 Abciximab 0.25 mg/kg IV bolus given 10–60 min before
start of PCI, followed by 0.125 mcg/kg/min (maximum 10
mcg/min) for 12 hours.
 Eptifibatide 180 mcg/kg IV bolus, repeated in 10 min,
followed by infusion of 2 mcg/kg/min for 18–24 hours after
PCI.
 Tirofiban 25 mcg/kg IV bolus, followed by an infusion of
44

45. Anticoagulants
 Patients undergoing primary PCI
 UFH or bivalirudin is preferred;
 In fibrinolysis,
 UFH, enoxaparin, or fondaparinux may be
administered.
45

46. Anticoagulants….UFH dosing
 UFH dose for primary PCI:
 50–70 units/kg IV bolus if GPI is planned and 70–
100 units/kg IV bolus if no GPI is planned;
 give supplemental IV bolus doses to maintain the
target activated clotting time (ACT).
 UFH dose for STEMI with fibrinolytics:
 60 units/kg IV bolus (max 4000 units), followed by
continuous infusion of 12 units/kg/h (max. 1000
units/h).
 Adjust to maintain target aPTT 1.5–2 times control
(50–70 s). 46

47. Dosing…for others
 Enoxaparin dose for STEMI:
 1 mg/kg SC Q 12–24 hours depending on renal function.
 For STEMI patients receiving fibrinolytics, enoxaparin 30 mg
IV bolus is followed immediately by 1 mg/kg SC Q12h if < 75
years (0.75 mg/kg SC Q12h if ≥75 years).
 Bivalirudin dose for PCI in STEMI:
 0.75 mg/kg IV bolus then 1.75 mg/kg/h continuous infusion.
 Discontinue at end of PCI or continue at 0.25 mg/kg/h if
prolonged anticoagulation is necessary.
 Fondaparinux dose for STEMI:
 2.5 mg IV bolus, followed by 2.5 mg SC daily starting on
hospital day 2. 47

48. Nitrates
 One SL NTG tablet (0.4 mg) should be administered
every 5 minutes for up to three doses to relieve
myocardial ischemia.
 ACEIs or βBs, should not be withheld for nitrates use
because the mortality benefit of nitrates is unproven.
 IV NTG initiated in all ACS with persistent ischemia,
HF, or uncontrolled high BP in the absence of CIs.
 IV NTG continued for approximately 24 h after ischemia
relieved
 The most significant adverse effects of nitrates are
 tachycardia, flushing, headache, and hypotension.
 Nitrate CI with oral PDE-5 inhibitors, such as sildenafil
48

49. β-Blockers
 A βB should be administered early in the care of
patients with STE ACS and continued indefinitely.
 Early administration of a βB within the first 24 hours
of hospitalization in patients lacking a
contraindication is a quality care indicator.
49

50. BB…
 Target resting HR is 50–60 beats/min; initial IV
therapy may be omitted, if appropriate.
 Metoprolol 5 mg by slow (over 1–2 min) IV bolus,
repeated Q 5 min for a total initial dose of 15 mg;
follow in 1–2 hours by 25–50 mg orally every 6 hours.
 Propranolol 0.5–1 mg slow IV push, followed in 1–2
hours by 40–80 mg PO every 6–8 hours.
 Atenolol 5 mg IV dose, followed 5 min later by a
second 5 mg IV dose, then 50–100 mg PO daily
beginning 1–2 h after the IV dose.
 For at least 3 years for normal EF, indefinitely if
50

51. Calcium Channel Blockers
 Administration of CCBs in the setting of STE ACS is
reserved for patients who have contraindications to
βBs and is given for relief of ischemic symptoms.
 In patients prescribed CCBs for treatment of
hypertension who are not receiving βBs and who do
not have a contraindication to βBs, the CCB should be
discontinued and a βB initiated.
 Nifedipine should be avoided because it has
demonstrated reflex sympathetic activation,
tachycardia, and worsened myocardial ischemia. 51

52. Early pharmacotherapy for NSTE-
ACS
 Generally similar to that of STEMI
 all patients with NSTE-ACS should be tted in the ED
with
 Morphine PRN in refractory patients
 IN Oxygen (if O2 saturation <90)
 sublingual ± IV NTG (IV in selected patients )
 DAT (Aspirin with P2y12 inhibitors)
 Anticoagulant (UFH or enoxaparin/fondaparinux/bivalirudin)
 PO β-blocker (in ED, within first 24 h) (IV in selected pnts)
 High-risk patients should proceed to early angiography and
may receive a GPI (optional with either UFH
or enoxaparin but should be avoided with bivalirudin). 52

53. 53

54. Fibrinolytic Therapy
 is not indicated in any patient with NSTE-ACS
 because increased mortality has been reported with
fibrinolytics compared with controls in clinical trials in
(patients with normal or ST-segment depression
ECGs).3
54

55. Aspirin
 Reduces the risk of death or developing MI by about
50% (compared with no antiplatelet therapy) in
patients with NSTE-ACS.
 Therefore, aspirin remains the cornerstone of early
treatment for all patients with ACS.
 Dosing of aspirin for NSTE-ACS is the same as that
for STEMI.
55

56. Anticoagulants
 UFH 60 units/kg IV bolus (max. 4000 units), followed
by a continuous IV infusion of 12 units/kg/h (max.
1000 units/h); titrate to maintain aPTT between 1.5
and 2 times control.
 Duration: continued for
 up to at least 48 hours for UFH,
 until the patient is discharged from the hospital (or 8
days, whichever is shorter) for either enoxaparin or
fondaparinux, or
 until the end of PCI or angiography procedure (or
up to 72 hours following PCI for bivalirudin). 56

57. Nitrates
 Similar indication and dose recommendation to STE
ACS
 BBs
 Recommendations are similar to STE ACS
 Calcium Channel Blockers
 Should not be administered to most patients.
 Agent selection and indication for NSTE-ACS is
identical to STEMI
57

58. 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
58

59. Late hospital care/secondary prevention
agents for both types of MI
59
All patients (ABAS)
1. Antiplatelet (ASA indefinitely +P2Y12 inhibitors ≥ 12
months)
2. BBs (within 24 hours of ED visit) indefinitely if no CI
3. ACEIs/ARBs
4. Statins (high-intensity)
5. NTG PRN
On selected pnts
1. Aldosterone antagonists
2. Clopidogrel
3. warfarin

60. Anticoagulants
 Warfarin should be considered in selected patients
following an ACS,
 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.
60

61. EVALUATION OF THERAPEUTIC
OUTCOMES
Monitoring parameters for efficacy of therapy
include:
 relief of ischemic discomfort;
 return of ECG changes to baseline; and
 absence or resolution of heart failure signs.
61