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Chapter 48
Drugs for Heart Failure
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Two Major Forms of Heart Failure
1. Heart failure with left ventricular (LV) systolic
dysfunction
2. Diastolic heart failure, also known as heart
failure with preserved LV ejection fraction
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Note: In this chapter, we will focus primarily
on the treatment of form #1
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Heart Failure
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Progressive, often fatal disorder
Characterized by left ventricular dysfunction,
reduced cardiac output, insufficient tissue
perfusion, and signs of fluid retention
Affects nearly 5 million Americans
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Pathophysiology of Heart Failure
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Inadequate tissue perfusion
Volume overload
Chronic hypertension
Myocardial infarction
Valvular heart disease
Coronary artery disease
Congenital heart disease
Dysrhythmias
Aging of the myocardium
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Pathophysiology of Heart Failure
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Cardiac remodeling
Physiologic adaptations to reduced cardiac
output (CO)
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Cardiac dilation
Increased sympathetic tone
Water retention and increased blood volume
Natriuretic peptides
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Drugs for Heart Failure
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Diuretics
RAAS inhibitors
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ACE inhibitors
Angiotensin II receptor blockers
Aldosterone antagonists
Direct renin inhibitors
Beta blockers
Digoxin
Other inotropic agents
Other vasodilators
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Fig. 48–2. The vicious cycle of maladaptive compensatory responses to a failing
heart.
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Fig. 48–3. American College of Cardiology/American Heart Association (ACC/AHA) Stage
and New York Heart Association (NYHA) Classification of Heart Failure.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Drugs Used to Treat Heart Failure
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Diuretics
Drugs that inhibit the renin-angiotensinaldosterone system (RAAS)
Beta blockers
Digoxin and other cardiac glycosides
Inotropic agents (other than cardiac
glycosides)
Vasodilators: other than ACE inhibitors and
angiotensin-receptor blockers (ARBs)
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Diuretics
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Thiazide diuretics
High-ceiling (loop) diuretics
Potassium-sparing diuretics
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Drugs That Inhibit the RAAS
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ACE inhibitors
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Hemodynamic benefits
• Arteriolar dilation
• Venous dilation
• Suppression of aldosterone release
 Impact on cardiac remodeling
• ACE inhibitors have favorable impact
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Drugs That Inhibit the RAAS
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ACE inhibitors (cont’d)
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Adverse effects
• Hypotension
• Hyperkalemia
• Intractable cough
• Angioedema
• Renal failure if patient has bilateral renal artery stenosis
• Can cause fetal injury
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Drugs That Inhibit the RAAS
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Angiotensin II receptor blockers
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Clinical trials have shown that ARBs improve LV
ejection fraction, reduce HF symptoms, increase
exercise tolerance, decrease hospitalization,
enhance quality of life, and reduce mortality
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Drugs That Inhibit the RAAS
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Aldosterone antagonists
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Spironolactone (Aldactone) and eplerenone
(Inspra)
Current studies recommend adding an
aldosterone antagonist to standard HF therapy in
patients with moderately severe or severe
symptoms
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Drugs That Inhibit the RAAS
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Direct renin inhibitors
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Benefits in HF should be equal to those of ACE
inhibitors or ARBs
Aliskiren (Tekturna) is being tested in HF
Not yet approved for HF treatment
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Beta Blockers
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Action
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With careful control of dosage, can improve
patient status
Protect from excessive sympathetic stimulation
Protect against dysrhythmias
Adverse effects
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Fluid retention or worsening of HF
Fatigue
Hypotension
Bradycardia or heart block
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Digoxin and Cardiac Glycosides
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Positive inotropic actions
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Increase myocardial contractile force
Alter electrical activity of the heart
Favorably affect neurohormonal systems
Second-line agents
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Inotropic Agents
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Sympathomimetics
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Dopamine (Intropin)
• Catecholamine
• Activates beta1-adrenergic receptors in the heart,
kidney, and blood vessels
• Increases heart rate
• Dilates renal blood vessels
• Activates alpha1 receptors
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Inotropic Agents
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Sympathomimetics (cont’d)
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Dobutamine
• Synthetic catecholamine
• Selective activation of beta1-adrenergic receptors
Phosphodiesterase inhibitors
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Inamrinone—inodilator
Milrinone (Primacor)
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Vasodilators
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Isosorbide dinitrate plus hydralazine
Intravenous vasodilators for acute care
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Nitroglycerin
• Principal adverse effects
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Sodium nitroprusside (Nitropress)
• Principal adverse effect
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Hypotension
Resultant reflex tachycardia
Profound hypotension
Nesiritide (Natrecor)
• Principal adverse effect
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Symptomatic hypotension
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Cardiac (Digitalis) Glycosides
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Digoxin (Lanoxin, Lanoxicaps, Digitek)
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Naturally occurring compound
Profound effects on the mechanical and electrical
properties of the heart
Increases myocardial contractility
Increased cardiac output
Adverse effect
• Can cause severe dysrhythmias
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Digoxin (Lanoxin)
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Effects
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Relationship of potassium to inotropic action
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Positive inotropic action on the heart
Increases the force of ventricular contraction
Increases myocardial contractility
Potassium levels must be kept in normal
physiologic range
Hemodynamic benefits
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Increased cardiac output
• Decreased sympathetic tone
• Increased urine production
• Decreased renin release
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Fig. 48–4. Ion fluxes across the cardiac cell membrane.
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Digoxin (Lanoxin)
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Neurohormonal benefits
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Modulates the activity of the neurohormonal
system
Suppresses renin release in the kidney
Decreases sympathetic outflow from the CNS
Increases the sensitivity of cardiac baroreceptors
Electrical effects
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Alters the electrical properties of the heart
• Increases the firing rate of vagal fibers
• Increases the responsiveness of the SA node to
acetylcholine
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Digoxin (Lanoxin)
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Adverse effects
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Cardiac dysrhythmias
Predisposing factors
• Hypokalemia
• Elevated digoxin level
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Narrow therapeutic range
• Heart disease
 Diagnosing digoxin-induced dysrhythmias
 Managing digoxin-induced dysrhythmias
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Digoxin (Lanoxin)
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Adverse effects (cont’d)
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Noncardiac adverse effects
• Anorexia, nausea, vomiting, fatigue
Measures to reduce adverse effects
• Education
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Digoxin (Lanoxin)
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Drug interactions
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Diuretics
ACE inhibitors and ARBs
Sympathomimetics
Quinidine
Verapamil
Pharmacokinetics
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Absorption
Distributed widely and crosses the placenta
Eliminated primarily by renal excretion
Half-life about 1.5 days
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Management of Heart Failure
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Stage A
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No symptoms of HF
No structural or functional cardiac abnormalities
Hypertension, CAD, diabetes, family history of
cardiomyopathy, personal history of alcohol
abuse, rheumatic fever, or treatment with a
cardiotoxic drug (eg, doxorubicin, trastuzumab)
Management directed at reducing risk
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Management of Heart Failure
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Stage B
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No signs and symptoms of HF
Goal of management is to prevent development of
symptomatic HF
Treatment is the same as for stage A with the
addition of ACE inhibitors or ARBs
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Management of Heart Failure
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Stage C
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Symptoms of HF
Structural heart disease
Four major goals
• Relieve pulmonary and peripheral congestive symptoms
• Improve functional capacity and quality of life
• Slow cardiac remodeling and progression of LV
dysfunction
• Prolong life
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Management of Heart Failure
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Stage C (cont’d)
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Drug therapy
• Diuretics
• ACE inhibitors and ARBs
• Aldosterone antagonists
• Beta blockers
• Digoxin
• Isosorbide dinitrate/hydralazine
Drugs to avoid
• Antidysrhythmic agents
• Calcium channel blockers
• NSAIDs
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Management of Heart Failure
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Stage C (cont’d)
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Device therapy
• Implanted cardioverter-defibrillators
• Cardiac resynchronization
 Exercise training
 Evaluating treatment
• Based on symptoms and physical findings
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Management of Heart Failure
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Stage D
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Marked symptoms of HF
Advanced structural heart disease
Repeated hospitalizations
Best solution is a heart transplant
• LV mechanical assist device used until heart is available
Management
• Control of fluid retention
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Loop diuretic, thiazide diuretic
Dopamine, dobutamine
• Beta blockers pose high risk for worsening HF
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