Chapter 48

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 48

Drugs for Heart Failure

2Copyright © 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 Note: In this chapter, we will focus primarily

on the treatment of form #1


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


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


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


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


Fig. 48–2. The vicious cycle of maladaptive compensatory responses to a failing heart.


Fig. 48–3. American College of Cardiology/American Heart Association (ACC/AHA) Stage and New York Heart Association (NYHA) Classification of Heart Failure.


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)


Diuretics Thiazide diuretics High-ceiling (loop) diuretics Potassium-sparing diuretics


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


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


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


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


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


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


Digoxin and Cardiac Glycosides Positive inotropic actions

Increase myocardial contractile force Alter electrical activity of the heart Favorably affect neurohormonal systems

Second-line agents


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


Inotropic Agents Sympathomimetics (cont’d)

Dobutamine• Synthetic catecholamine• Selective activation of beta1-adrenergic receptors

Phosphodiesterase inhibitors Inamrinone—inodilator Milrinone (Primacor)


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


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


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


Fig. 48–4. Ion fluxes across the cardiac cell membrane.


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


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


Digoxin (Lanoxin) Adverse effects (cont’d)

Noncardiac adverse effects• Anorexia, nausea, vomiting, fatigue

Measures to reduce adverse effects• Education


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


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


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


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


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


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


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

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Chapter 48