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Chapter 48
Drugs for Heart Failure
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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 Note: In this chapter, we will focus primarily
on the treatment of form #1
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Heart Failure 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
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Pathophysiology of Heart Failure 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 Cardiac remodeling Physiologic adaptations to reduced cardiac
output (CO) Cardiac dilation Increased sympathetic tone Water retention and increased blood volume Natriuretic peptides
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Drugs for Heart Failure Diuretics RAAS inhibitors
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.
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Drugs Used to Treat Heart Failure Diuretics Drugs that inhibit the renin-angiotensin-
aldosterone 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 Thiazide diuretics High-ceiling (loop) diuretics Potassium-sparing diuretics
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Drugs That Inhibit the RAAS ACE inhibitors
Hemodynamic benefits• Arteriolar dilation• Venous dilation• Suppression of aldosterone release
Impact on cardiac remodeling• ACE inhibitors have favorable impact
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Drugs That Inhibit the RAAS ACE inhibitors (cont’d)
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 Angiotensin II receptor blockers
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 Aldosterone antagonists
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 Direct renin inhibitors
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 Action
With careful control of dosage, can improve patient status
Protect from excessive sympathetic stimulation Protect against dysrhythmias
Adverse effects Fluid retention or worsening of HF Fatigue Hypotension Bradycardia or heart block
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Digoxin and Cardiac Glycosides Positive inotropic actions
Increase myocardial contractile force Alter electrical activity of the heart Favorably affect neurohormonal systems
Second-line agents
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Inotropic Agents Sympathomimetics
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 Sympathomimetics (cont’d)
Dobutamine• Synthetic catecholamine• Selective activation of beta1-adrenergic receptors
Phosphodiesterase inhibitors Inamrinone—inodilator Milrinone (Primacor)
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Vasodilators Isosorbide dinitrate plus hydralazine Intravenous vasodilators for acute care
Nitroglycerin• Principal adverse effects
Hypotension Resultant reflex tachycardia
Sodium nitroprusside (Nitropress)• Principal adverse effect
Profound hypotension Nesiritide (Natrecor)
• Principal adverse effect Symptomatic hypotension
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Cardiac (Digitalis) Glycosides Digoxin (Lanoxin, Lanoxicaps, Digitek)
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) Effects
Positive inotropic action on the heart Increases the force of ventricular contraction Increases myocardial contractility
Relationship of potassium to inotropic action Potassium levels must be kept in normal
physiologic range Hemodynamic benefits
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) Neurohormonal benefits
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 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) Adverse effects
Cardiac dysrhythmias Predisposing factors
• Hypokalemia• Elevated digoxin level
Narrow therapeutic range• Heart disease
Diagnosing digoxin-induced dysrhythmias Managing digoxin-induced dysrhythmias
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Digoxin (Lanoxin) Adverse effects (cont’d)
Noncardiac adverse effects• Anorexia, nausea, vomiting, fatigue
Measures to reduce adverse effects• Education
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Digoxin (Lanoxin) Drug interactions
Diuretics ACE inhibitors and ARBs Sympathomimetics Quinidine Verapamil
Pharmacokinetics 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 Stage A
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 Stage B
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 Stage C
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 Stage C (cont’d)
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 Stage C (cont’d)
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 Stage D
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 Loop diuretic, thiazide diuretic Dopamine, dobutamine
• Beta blockers pose high risk for worsening HF