Ischemic Heart Disease

1. Pharmacotherapy Cardiovascular Disorders
Lesson 3
Ischemic Heart Disease
By: Tsegaye Melaku
[B.Pharm, MSc, Clinical Pharmacist]
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et +251913765609January, 2019

2.  Session hits
 Risk factors for dev’t of IHD.
 Pathophysiology of chronic stable angina Vs ACS
 Clinical picture specific patient.
 Appropriate lifestyle modifications and pharmacologic therapy
 Appropriate therapeutic regimen
 Monitor & evaluate
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3.  IHD:
– Aka coronary heart disease (CHD) /Coronary arterial
diseases(CAD)
– Refers to a decreased supply of oxygenated blood to
heart muscle.
– Caused by stenosis/narrowing( ≥1major coronary
arteries)
» Most commonly by atherosclerotic plaques
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4.  The major epicardial coronary arteries
– Left main,
– Left anterior descending,
– Left circumflex,
– Right coronary arteries
» Atherosclerosis leading to obstructive lesions in
one or more of them or their branches
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5.  Vasospasm (no or minimal atherosclerotic plaques): may further
constrict blood flow  contribute to angina    to ACS
– Aka variant or Prinzmetal angina : uncommon
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6.  Plaques impede coronary blood flow distal to the coronary artery
narrowing
– Deprived of sufficient oxygen to meet oxygen demand.
 IHD: results from an imbalance between myocardial oxygen supply and
oxygen demand
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IHD: an imbalance between myocardial oxygen supply and oxygen demand

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11.  Most common symptom of IHD
 It is discomfort in the chest that occurs when the blood supply to the
myocardium is compromised.
 It is chronic occurrence of chest discomfort
– Due to transient myocardial ischemia with physical
exertion or
– Other conditions that increase oxygen demand.
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12.  IHD affects over 15 million Americans
 The leading cause of death for both men and women : US data
 Incidence: higher in middle-aged men compared with women
– However, rate increases 2-3 fold in women after
menopause
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13.  Chronic stable angina: initial manifestation of IHD in about 50% of
patients,
– ACS: first sign of IHD in other patients.
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14.  Hypertension, diabetes,
 Dyslipidemia, cigarette smoking
 Physical inactivity, obesity: independently increase the risk for IHD
 Multiple risk factors: 5- 7x risk increases
– Metabolic syndrome
» Constellation of hypertension, abdominal obesity,
dyslipidemia, and insulin resistance
» Increase risk 2 fold
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16.  Patients must meet at least three of the following criteria: AHA definition
– Waist circumference: ≥40 inches/102 cm in men & ≥35 inches /89
cm women.
– TG ≥150 mg/dL) or active treatment to lower triglycerides.
– Low HDL-C < 40 mg/dL in men and < 50 mg/dL in women) or active
treatment to raise HDL-C
– SBP ≥130 mm Hg, DBP≥85 mm Hg, or on antihypertensive therapy.
– FBS ≥100 mg/dL or on antidiabetics.
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17.  Consider the determinants of oxygen supply & demand
 ↑in HR, cardiac contractility, LVwall tension   ↑MVO2
– Ventricular wall tension: is a function of BP, LV end-diastolic volume,
ventricular wall thickness.
 O 2 supply ↓ed:
– Reductions in coronary blood flow (2° to atherosclerotic plaques/
vasospasm/thrombus formation
– Arterial oxygen content (2° to hypoxia)
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18.  Coronary arteries fill during diastole,
 ↓ in diastolic filling time (e.g, tachycardia)  ↓ coronary perfusion &
supply
 Anemia/CO poisoning/ cyanotic congenital HD   ↓ oxygen
carrying capacity of the blood,   ischemia
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Endothelial cells : form a selective barrier between the vessel wall and blood contents.
Vascular smooth muscle here

20.  Atherosclerotic lesions form in sub-endothelial space in the intimal layer
 Endothelial damage& dysfunction,
– Commonly caused by HTN, DM,& smoking,
– Allow LDL-C & inflammatory cells (e.g, monocytes & T lymphocytes)
migration from plasma   sub-endothelial space
 Process initiation: Monocytes-derived macrophages ingesting
lipoproteins to form foam cells.
 Macrophages also secrete growth factors   promote smooth
muscle cell migration from the media to the intima.
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22.  Early atherosclerosis: fatty streak [lipid-laden macrophages + smooth
muscle cells] is formed
 Accumulation of foam cells, smooth muscle cells, and necrotic debris 
enlarge fatty streaks.
 Collagen matrix forms a fibrous cap  covers lipid core
of the lesion    atherosclerotic plaque  affect blood flow
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23.  Occlusion of ≥70% major coronary artery or 50% or more of the left
main coronary artery  induced angina pain during exercise
 By and large hallmark feature: established atherosclerotic plaque in
one or more of the major coronary arteries.
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 Stable plaques
 Small lipid core
 thick fibrous cap
 Multiple layer of SM
 Unstable plaques
 Large lipid core
 Thin fibrous cap
 Single layer of SM

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27.  Aka prinzmetal or variant angina.
 Results from spasm (or vasoconstriction) of a coronary artery in the
absence of significant atherosclerosis.
 Usually occurs at rest [esp. in early morning hrs].
 Transient vasospasm
– But, may persist long   cause MI
 Most of the patients are younger ( Unlike unstable angina)
– Often do not possess classic risk factors for IHD
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28.  Cause of variant angina
– Mostly: unclear
– But, may involve
– Vagal withdrawal,
– Endothelial dysfunction,
– Paradoxical response to agents that normally cause
vasodilation.
 Its precipitants: cigarette smoking, cocaine or amphetamine use,
hyperventilation, & exposure to cold temperatures.
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29.  Distinguish b/n chronic stable from unstable angina
– The latter associated with a greater risk for MI & death
– Requires hospitalization for more aggressive treatment.
 Chronic stable angina:
– Due primarily to increases in MVO2 rather than acute changes in
oxygen supply.
– Sxs are typically reproducible[provoked by exertion/exercise/stress.
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30.  ACS:
– Due to an acute decrease in coronary blood flow [inadequate
oxygen supply].
– Prolonged symptoms [often occurring at rest].
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31.  Most patients are not in acute distress
 If patients in acute distress suspect ACS
 X-rize pain: quality, location, duration, provoking/relieving factors
 Pressure/heaviness/tightness/squeezing in anterior chest area
 Sharp pain: not a typical symptom
 Pain radiate to the neck, jaw, shoulder, back, or arm.
– Accompanied by dyspnea, NV, or diaphoresis.
– Pain typically persists for several minutes
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36.  Sxs provoked by exertion/emotional stress
– Cold temperatures & heavy meals
– Relieved by rest or SL nitroglycerin.
 Atypical sxs[women, Elderly, DM]
– Indigestion, gastric fullness, back pain, SOB
– Diaphoresis, nausea, fatigue, and dizziness
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37.  Detailed history of symptoms
 Physical examination,
 Laboratory analysis
– FBS, HA1C, hemoglobin, lipid panel,
– Organ function (RFT, LFT, TFT)
– Cardiac biomarkers
 Diagnostic tests
– ECG, ECHO, X-ray, MRI, CT scan, angiography
– Stress testing [exercise or pharmacologic]
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39.  Goal of therapy
– Prevent acute coronary syndrome and death
– Alleviate acute symptoms of myocardial ischemia
– Prevent recurrent symptoms of MI
– Prevent progression of the disease
– Reduce complications of IHD
– Avoid or minimize adverse treatment effects
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40.  Aggressively modify cardiovascular risk factors
 Slow the progression of coronary atherosclerosis
 Stabilize existing atherosclerotic plaques
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Primary or secondary prevention of ACS/CVA

41.  Rx: balance between myocardial oxygen demand and supply.
– Primary Rx: reducing oxygen demand
– No response: revascularization by PCI & CABG: restore coronary
blood flow
 Appropriate drug dosing & monitoring: crucial
– Initiation/titration
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43.  Smoking cessation/avoidance of second-hand smoke,
 Dietary modifications,
 Increased physical activity,
 Weight loss
 Cigarette smoking: single most preventable cause of IHD & IHD-
related death
– Smoking: attenuate the anti-anginal effects of drug therapy.
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45.  Considered when:
– Medical therapy fails
– Symptoms are unstable, or
– Extensive coronary atherosclerosis (e.g, >70% occlusion of
coronary lumen)
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46.  Different methods:
a) Percutaneous transluminal coronary angioplasty(PTCA)
– Balloon inflation
b) Intracoronary bare metal stent placement
– Stents are thrombogenic(esp. until endothelialized
– DAPT: required till endothelized (~12 months)
c) Intracoronary drug-eluting stent placement
– Low concentrations of an anti-proliferative drug
» (paclitaxel, everolimus, sirolimus, or zotarolimus)
d) Rotational atherectomy
– Special cut away the atherosclerotic plaque
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49.  As an alternative to PCI
 May as open-heart surgery
 Considered
– In extensive coronary atherosclerosis (>70% occlusion of ≥3
coronary arteries)
– Refractory to optimal medical treatment.
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52.  Control risk factors: dyslipidemia, hypertension, & diabetes
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53.  High-intensity statin
– Clinical ASCVD & without clinical ASCVD LDL-C ≥190 mg/dL;
 Moderate to high-intensity
– Age >40 + diabetes
– Candidate who didn’t tolerate side effects of high intensity
– LDL-C <190mg/dL + age >40yrs +
– 10-year ASCVD risk of 7.5% in the absence of diabetes
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54.  Statin
– Anti-inflammatory effects,
– Antiplatelet effects/stabilize plaque
– Improvement in endothelial function,
– Improvement in arterial compliance and tone
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Statin reduces the risk of MACE by 21%
Considered in all patients with IHD, (esp. elevated LDL-Cor diabetes]

55.  Hypertension
– Minimize the risk of MACE
– Goal of <140/90 mm Hg
– Rx: ACEI/ARBs ± CCB ± thiazide diuretics
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56.  Antiplatelet Agents
– Aspirin: prevent production of TXA2
– Considered in all patients, in no contraindications
– Dose: 75 to 162 mg
– Alternative: glycoprotein IIb/IIIa receptors inhibitors
– Clopidogrel [75mg], prasugrel, or ticagrelor
– DAPT:
– ACS
– Following PCI with stent placement [at least for 1yr, ACS +PCI)
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Greater control, but high risk of bleeding

57.  Ang-II
– Potent vasoconstrictor
– Stimulates the production of aldosterone.
– HTN & sodium& water retention increasing ventricular wall tension),
– Cause endothelial dysfunction, promote thrombus formation,
– Cause myocardial fibrosis.
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ACEIs/ARBs antagonize these all effects

58.  In absence of contraindications, ACEI
– Should be considered in all patients with IHD,
– Particularly those hypertension, diabetes mellitus, chronic kidney
disease, left ventricular dysfunction, history of MI,
 Side effects:
– Hyperkalemia, deterioration in renal function, & angioedema
– Vasoconstriction of efferent arteriole
– Chronic cough
 CI: Pregnancy, AKI, renal artery stenosis
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60.  0.3 to 0.4 mg dose every 5 minutes
 To relieve acute symptoms
 Anti-anginal effect within 1 to 3 minutes,
 Sublingual tablets or spray
 Nitrates NO ↑cGMP  ↑ca2+  smooth muscle relaxation
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61.  1˚rly venodilation ↓preload
– ↓ventricular volume & wall tension  MVO2
 In higher dose: arterial dilation/afterload/↓BP
– ↑myocardial oxygen supply [dilate epicardial coronary arteries &
collateral vessels].
 Isosorbide dinitrate: long acting  effects lasting up to 2 hours
 Don’t use with 24 to 48 hours 5-PDE inhibitors
 Side effects: hypotension, dizziness, or lightheadedness.
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63.  Prevent ischemic symptoms by: β-blockers, CCBs, nitrates, & ranolazine
 They
– Decrease the frequency of angina
– Delay the onset of angina during exercise
 No evidence as if these agents prevent ACS or improve survival in
stable angina
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65.  ↓HR & cardiac contractility MVO2
 ↓ BP & ventricular wall tension [inhibition of renin release]
 Slow HR   prolong diastole increasing coronary blood flow.
 Do not improve myocardial oxygen supply.
 Avoid those with ISA (e.g, acebutolol, pindolol, penbutolol): not effective
 Dosing & titration: based on HR
– Resting HR: 50-60bpm
– Exercise HR: max 100bpm/<20bpm above resting HR
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66.  Sidé effets: fatigue, sleep disturbances, malaise, depression, and sexual
dysfunction.
 CI: severe bradycardia (HR<50 beats/min) or AV conduction defects,
asthma, bronchospastic disease, & severe depression
 Cautions: diabetes or acute HF, Abrupt withdrawal
 DDI: digoxin, verapamil, diltiazem, etc
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68.  Inhibit calcium entry into vascular smooth muscle & cardiac cells
relaxation
 On vascular smooth muscle cells  systemic vasodilation  ↓ afterload
 On cardiac cells   ↓ cardiac contractility.
 ↓ MVO2 : ↓ wall tension (through reductions in afterload) & ↓ cardiac
contractility.
 All CCBs ↓supply: dilating coronary arteries
 Non-DHP: slow SA & AV nodal conduction, ↓HR ↓MVO2
– More effective than DHP for angina(-ve inotropic effect)
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70.  Products produce effects within 30 to 60 minutes
 Issue: tolerance with continuous use
 First 24 hours of continuous nitrate therapy loss of anti-anginal effect
– Generation of free radicals that degrade nitric oxide
 Monotherapy should be avoided.
– Reflex ↑ in sympathetic activity & HR
– Add β-blocker ± CCB
 Side effects: postural hypotension, dizziness, flushing, headache
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72.  Dose: 500 mg -1000mg Bid
 Anti-ischemic agent
 MOA: unknown/unclear
– Inhibit late inward sodium current during plateau phase of the
cardiac action potential.
 For angina refractory to other antianginal medications
 Side effects: dizziness, constipation, headache, nausea. Syncope
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76.  Efficacy & safety
– Clinical signs and symptoms
– Laboratory tests and investigations
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