Stable Ischemic Heart Disease

By: T/haimanot Fentie (Assistant Prof. of Clinical Pharmacy)

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 Introduction
 Ischemic heart disease (IHD) is also called coronary
heart disease (CHD) or coronary artery disease
(CAD).
 The term ischemic refers to a decreased supply of
oxygenated blood to the myocardium resulting from
coronary artery narrowing or obstruction.
 Common clinical manifestations of IHD include
 chronic stable angina and
 the acute coronary syndromes (ACS) of
 unstable angina (UA),
 non–ST-segment elevation myocardial infarction (NSTEMI) &
 ST-segment elevation myocardial infarction (STEMI).
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 IHD results from an imbalance between myocardial
oxygen (O2) demand & supply .

Normally, coronary blood flow ↑ in response to ↑ in myocardial O2

demand, but NOT in patients with IHD, resulting in angina.
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 Major Risk Factors for IHD
Modifiable Non-modifiable
1. Cigarette smoking 1. Age ≥ 45 years for men, age ≥ 55
2. Dyslipidemia years for women
 ↑ LDL, TG or total cholesterol 2. Gender (men & postmenopausal
women)
 ↓ HDL cholesterol
3. Family history of premature
3. Diabetes
CVD, defined as CVD in
4. Hypertension
 a male 1st-degree relative (ie, father
5. Physical inactivity or brother) < 55 years or
6. Obesity (BMI ≥ 30 kg/m2)  a female 1st-degree relative (ie,
7. Low daily fruit & vegetable mother or sister) < 65 years
Consumption
8. Alcohol overconsumption
Note: Smoking cessation restores the risk of IHD to that of a nonsmoker within ~15 years.
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 Pathophysiology
 SIHD results from ↑ed O2 demand (MVo2) or ↓ed O2
supply.
 A doubling in HR, ventricular contractility, or wall tension
requires a 50% ↑ in coronary blood flow to maintain O2
supply.
 Endothelial damage & dysfunction, commonly caused by
hypertension, diabetes, dyslipidemia & smoking
contribute to development of atherosclerosis.
 Progressive ↓ in vessel radius with coronary
atherosclerosis
 impairs coronary blood flow and
 causes angina pectoris when myocardial O2 demand ↑, as
with exertion.
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 Angina pectoris may also occur because of abrupt ↓ in
blood flow due to coronary thrombosis (unstable
angina) or localized vasospasm (variant or Prinzmetal
angina) without ↑ed O2 demand.
 Ischemic episodes may be
 more common in the morning hours (due to circadian
release of vasoconstrictors) and
 precipitated by cold exposure & emotional stress.

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 Clinical Presentation
 The five components used to characterize chest pain are
 quality, location, duration, provoking factors, & mitigating
factors.
 Chest pain described as a sensation of pressure,
heaviness, tightness, or squeezing in the anterior chest
area.
 Sharp pain & pain reproducible by palpation are not typical
symptoms of angina.
 Pain may
 Radiate to the left neck, jaw, shoulder, back, or arm.
 Be accompanied by dyspnea, nausea, vomiting, or
diaphoresis.
 Persist for 5–10 minutes, but <20 minutes.
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 Precipitating factors include:
 Exertion (eg, walking, climbing stairs), Exercise.
 Cold environment.
 Walking after a meal.
 Emotional upset, Fright, Anger.
 Sexual activity.
 Relief occurs with rest & within 5–10 min of taking
nitroglycerin.
 Variant (Prinzmetal) angina may be associated
with pain at rest, especially in the early morning
hours.
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Diagnosis
 Obtain medical history to determine:
 Quality of chest pain.
 Precipitating factors.
 Duration.
 Pain radiation.
 Response to nitroglycerin or rest.
 Assess personal & family history of risk factors for coronary
heart disease.
 Cardiac examination may reveal:
 Abnormal precordial systolic bulge.
 Decreased intensity of S1
 Paradoxical splitting of S2
 Presence of S3 or S4
 Apical systolic murmur.
 Diastolic murmur.
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 Laboratory Tests
 Hemoglobin, fasting glucose, fasting lipoprotein panel to
assess CV risk factors
 Cardiac troponin (I or T) is the most sensitive biomarker to
detect myocardial damage
 elevated in MI but typically normal in SIHD and UA.
 Other Diagnostic Procedures
 A 12-lead electrocardiogram (ECG)
 often normal at rest
 Exercise tolerance testing (ETT) or “stress test”
 is considered positive for IHD if the ECG shows at least a 1-mm
deviation of the ST segment (depression or elevation).
 Coronary angiography
 detects the location & degree of atherosclerosis
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Desired Outcomes
 The major goals for the treatment of SIHD are to:
 Prevent ACS & death
 Alleviate acute symptoms of angina
 Reduce the number of ischemic episodes
 Prevent progression of the disease or atherosclerosis
 Reduce complications of IHD such as MI, heart failure &
stroke
 Avoid or minimize adverse treatment effects

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General Approach to Treatment
 Primary strategies for preventing ACS and death
(eg, primary or secondary prevention) are to:
 Aggressively modify cardiovascular risk factors
 through lifestyle changes & pharmacologic therapy.
 Slow the progression of coronary atherosclerosis
 Stabilize existing atherosclerotic plaques
 Drug treatment is primarily used to ↓ O2 demand,
whereas revascularization by PCI & CABG restore
coronary blood flow, improving myocardial O2
supply.

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General treatment strategies for angina

Angina symptoms

Antianginal therapy Diagnostic workup

»β-Blocker »History & physical
»Calcium channel blocker »Electrocardiogram
»Nitrates »Stress testing
»Ranolazine »Coronary angiogram

Primary & secondary prevention Control risk factors

»Lifestyle modifications »Cigarette smoking
»Antiplatelet therapy »Hypertension
»ACE-I or ARB »Dyslipidemia
»β-Blocker »Obesity
»Statin »Diabetes

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Treatment Algorithm for stable ischemic heart disease

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Lifestyle Modifications
Smoking cessation,
Dietary modifications,
Increased physical activity, &
Weight loss

Reduce CV risk factors,

Slow progression of IHD, &
Decrease risk of SIHD-related complications.

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Pharmacologic Therapy
 Medical therapy is preferred as the initial treatment
strategy.
 Improve mortality in patients with SIHD by providing
guideline-directed medical therapy (GDMT).
 The following mnemonic, developed for patients with
chronic stable angina, can be applied to all patients
with CHD.
 A = Aspirin & antianginal therapy
 B = β-Blocker & BP control
 C = Cigarette smoking & cholesterol
 D = Diet & DM management
 E = Education & exercise
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Risk factor Identification & modification
1. Dyslipidemia
 All patients with known atherosclerotic CVD, such
as SIHD, should receive high-intensity statin
therapy, regardless of baseline LDL cholesterol.
 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 therapy,
should receive moderate-intensity statin therapy.

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2. Hypertension:
 If BP is ≥130/80 mm Hg, institute drug therapy in
addition to or after a trial of lifestyle modifications.
 Drug selection in SIHD includes agents typically
used to treat other aspects of the disease.
 β-Blockers (except atenolol & β-blockers with ISA),
ACE inhibitors, or ARBs are all recommended as
first-line therapy.
 CCBs can be added if additional therapy is needed.
 Thiazide diuretics could also be an option.

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3. Diabetes:
 SGLT2 inhibitors (empagliflozin & canagliflozin)
&
 GLP-1 receptor agonists (liraglutide, semaglutide,
& dulaglutide),
 improve CV outcomes in patients with clinical ASCVD
or at high risk for IHD.
 Therapy with rosiglitazone should not be initiated
in patients with SIHD.

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4. Smoking cessation:
 Smoking cessation & avoidance of exposure should
be encouraged for all patients with SIHD.
 Follow-up, referral to special programs, and
pharmacotherapy are recommended, as is a
stepwise strategy for smoking cessation
 (Ask, Advise, Assess, Assist, Arrange, Avoid).
 Nicotine replacement therapy.
 Sustained release bupropion.

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5. Weight Management:
 BMI and/or waist circumference should be
assessed at every visit, and an appropriate
intervention indicated to maintain or achieve
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 a BMI between 18.5 & 24.9 kg/m and
 a waist circumference <102 cm in men & <88 cm in
women.
 The initial goal of weight loss therapy should be to
reduce body weight by ~5 to 10% from baseline.
 With success, further weight loss can be attempted if
indicated.
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Antiplatelet therapy
 Antiplatelet therapy with aspirin is recommended in
all patients with or at risk for SIHD, in the absence of
contraindications.
 Guideline recommendations:
 Aspirin 75–162 mg daily, continued indefinitely.
 Daily doses >162 mg offer no additional benefit but ↑ bleeding risk.
 Clopidogrel 75 mg daily is a reasonable alternative when
aspirin is contraindicated (e.g., allergy).
 Dual antiplatelet therapy with aspirin & clopidogrel
might be reasonable following intracoronary stent
placement, after treatment for ACS and in certain high-
risk patients with SIHD.
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Dosing & Duration of Dual Antiplatelet Therapy (DAPT)
in SIHD
Clinical Scenario Aspirin P2Y12 Inhibitors Reasonable to:

SIHD treated with 325 mg before PCI; Clopidogrel for 1 Extend clopidogrel
PCI & BMS placed Starting day 2, 75– month for > 1 month for
100 mg/day those at low risk of
indefinitely bleeding
SIHD treated with 325 mg before PCI; Clopidogrel for 6 Discontinue
PCI & DES placed Starting day 2, 75– months clopidogrel after 3
100 mg/day months in those at
indefinitely high risk of
bleeding
Extend clopidogrel
for > 6 months for
those at low risk of
bleeding
BMS = bare metal stent; DAPT = dual antiplatelet therapy; DES = drug-eluting stent; PCI =
percutaneous coronary intervention; SIHD = stable ischemic heart disease.
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 ACE Inhibitors
 ACE inhibitors stabilize coronary plaque, restore
endothelial function, inhibit vascular smooth
muscle cell growth, ↓ macrophage migration, and
possibly possess some antioxidant activities.
 Guideline recommendations:
 Use ACE inhibitors in patients with SIHD who also
have hypertension, diabetes, HFrEF, history of MI, or
CKD, unless contraindicated.
 ARBs are recommended for the same patient populations if
they are intolerant to ACE inhibitors (e.g., cough or
angioedema).
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 Short-acting nitrates
 First-line for acute symptomatic relief of angina.
 Formulations: tablets, spray, buccal products.
 Nitroglycerin sublingually may be used 2–5 min
prior to activities that predictably precipitate attacks.
 At the onset of an angina attack, a 0.3 to 0.4 mg dose
of nitroglycerin may be repeated every 5 minutes up
to 3x or until symptoms resolve.
 All patients with SIHD should be prescribed
sublingual nitroglycerin and educated regarding its
use.

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Counseling points for sublingual nitroglycerin use
 The seated position is generally preferred when using
nitroglycerin because the drug may cause dizziness.
 Seek emergent care if symptoms are unimproved or
worsen 5 minutes after the first dose.
 Keep nitroglycerin tablets in the original glass container
and close the cap tightly after use.
 Repeated use of nitroglycerin is not harmful or addictive.
 Nitroglycerin should not be used
 within 24 hours of taking sildenafil or vardenafil or
 within 48 hours of taking tadalafil because of the potential
for life-threatening hypotension.
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 β-Blockers
 Blockade of β1 -receptors in the heart & kidney reduces
HR, contractility, & BP, thereby decreasing MVo2.
 However, β-blockers do not improve myocardial O2 supply.
 Effective in reducing both symptomatic and silent
episodes of myocardial ischemia.
 β-Blockers are recommended over CCBs for initial
control of angina episodes.
 Ideal candidates:
 physical activity figures prominently in anginal attacks
 coexistent hypertension
 history of supraventricular arrhythmias or post-MI angina
 anxiety associated with angina
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 β-Blocker dose is titrated to lower
 the resting HR to 50–60 beats/min and
 the exercise HR to < 100 beats/minute.
 Agents with intrinsic sympathomimetic activity are not
preferred.
 β-Blockers are contraindicated in patients with
 preexisting bradycardia (HR< 50 beats/min), hypotension,
2nd- or 3rd-degree AV block,
 uncontrolled asthma,
 severe PAD,
 hypotension,
 HFrEF with unstable fluid status, and
 diabetes with frequent episodes of hypoglycemia.
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CCBs
 All CCBs ↓ MVo2 by reducing wall tension via
lowering arterial BP & minimal reduction in
contractility.
 CCBs also provide some increase in supply by
inducing coronary vasodilation & preventing
vasospasm.
 Because of their negative chronotropic effects,
verapamil & diltiazem are more effective
antianginal agents than the dihydropyridine CCBs.
 CCBs are recommended as alternative treatment
in SIHD when β-blockers are contraindicated or not
tolerated.
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 Short-acting agents should not be used because of
risk of reflex tachycardia.
 Ideal candidates
 contraindications/intolerance to β-blockers
 coeixting conduction system disease (except verapamil,
diltiazem)
 Prinzmetal angina
 peripheral vascular disease
 concurrent HTN
 Avoid verapamil & diltiazem in patients with HFrEF
due to negative inotropic effects.
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 Long-acting nitrates
 Mostly venodilation, leading to reduced preload,
myocardial wall tension, and MVo2.
 Nitrates also ↑ oxygen supply.
 Arterial vasodilation produces reflex tachycardia.
 can be mitigated with concomitant β-blocker therapy.
 Long-acting nitrates should be added to baseline
therapy with either a β-blocker or CCB, or a
combination of the two.
 Major limitation: tolerance (loss of antianginal
effects) with continuous use.
 Provide nighttime nitrate-free interval of 8–12 hours per
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day or longer to maintain efficacy.
 Nitrates should not be used routinely as
monotherapy for stable IHD because of the
 lack of angina coverage during the nitrate-free interval,
 lack of protection against circadian rhythm (nocturnal)
ischemic events, and
 potential for reflex tachycardia.
 Monotherapy with nitrates may be appropriate in
low BP at baseline or symptomatic hypotension
with low doses of β-blockers or CCBs.
 Concomitant β-blocker or diltiazem therapy can
prevent rebound ischemia during the nitrate-free
interval.
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Ranolazine
 Ranolazine is effective as monotherapy or as add-on therapy.
 Reserved for patients who cannot tolerate any of the
traditional agents due to hemodynamic or other adverse
effects.
 Use when BP or HR is too low to add β-blockers, CCBs,
and/or nitrates.
 The initial ranolazine dose is 500 mg twice daily, increased
to 1000 mg twice daily within the next 1–2 weeks if tolerated.
 It can be combined with a β-blocker when initial treatment
with β-blockers alone is unsuccessful.
 Ranolazine interacts with simvastatin metabolism and
should not be used together.

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Interventional Approaches to Revascularization
 Percutaneous Coronary Intervention (PCI)
 Involve the placement of a stent.
 Indicated when
 optimal medical therapy fails,
 symptoms are unstable, or
 extensive coronary atherosclerosis is present (eg, > 70%
occlusion of coronary lumen).
 Coronary Artery Bypass Graft Surgery (CABG)
 Open-heart surgery, generally reserved for patients with
 extensive coronary atherosclerosis (generally > 70%
occlusion of ≥3 coronary arteries) or
 refractory to optimal medical treatment.
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Treatment of Variable threshold angina &
Prinzmetal’s angina
 Caused by imbalance between vasodilators (PG I2, NO)
& vasoconstrictors (endothelin, AT II)
 Nitrates & CCBs are effective agents for reducing
vasospasm.
 CCBs may be preferred b/c they are dosed less frequently.
 Most patients respond well to SL NTG for acute attacks.
 Nifedipine, verapamil, & diltiazem are all equally
effective as single agents for the initial management of
coronary vasospasm.
 If unresponsive to CCBs alone, add nitrates.
 β-blockers should be avoided because they may worsen
vasospasm due to unopposed α1- receptor stimulation.
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 Monitoring
 Patients may need to be evaluated every 1–2 months until
goals are achieved.
 Then, follow-up every 6–12 months would be appropriate.
 After patient optimized on medical therapy, symptoms
should improve over 2–4 weeks and remain stable until
disease progresses.
 Document the following:
 Number of angina episodes.
 weekly Sub Lingual nitroglycerin use.
 Improvement in exercise capacity.
 Consider using Seattle Angina Questionnaire, Specific
Activity Scale, and Canadian Cardiovascular Society
classification system to assess symptoms.
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 Objective assessment of control can be obtained by
a follow-up ETT with or without cardiac imaging.
 Patients should be instructed to seek emergent care
for ACS if symptoms of angina
 last longer than 20 to 30 minutes,
 do not improve after 5 minutes of using sublingual
nitroglycerin, or
 worsen after 5 minutes of using sublingual nitroglycerin.
 Treatment with antiplatelet (aspirin or clopidogrel),
lipid-lowering, and neurohormonal-modifying
medications for SIHD is generally lifelong.
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