Ischemic heart disease is caused by a decreased supply of oxygenated blood to the heart muscle, usually due to atherosclerotic narrowing of one or more coronary arteries. It results in an imbalance between myocardial oxygen supply and demand. Treatment involves aggressively modifying risk factors, stabilizing plaques, and restoring blood flow through revascularization or pharmacotherapy to balance oxygen supply and demand. Pharmacotherapy includes agents that reduce myocardial oxygen demand such as beta-blockers and calcium channel blockers, as well as those that increase supply such as nitrates, statins, and renin-angiotensin system inhibitors. Close monitoring is needed to optimize therapy and prevent complications.

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
2

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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