Medication Summary
The goals of pharmacotherapy include symptom relief, improved cardiac output, shortened hospital stay, fewer emergency department visits, reversal of injury process, and decreased mortality. Drug classes used include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, beta-blockers, aldosterone antagonists, cardiac glycosides, diuretics, nitrates, vasodilators, sacubitril-valsartan, ivabradine, antiarrhythmics, and inotropic agents.
In cases of dilated cardiomyopathy secondary to myocarditis, corticosteroids have been suggested to be helpful in decreasing inflammation; however, the Multicenter Myocarditis Treatment Trial showed no benefit in the use of corticosteroids and azathioprine for treatment of biopsy-proven inflammation in dilated cardiomyopathy. Some smaller uncontrolled studies have shown benefit, but these results have not been confirmed with a controlled study.
ACE Inhibitors
Class Summary
Use of ACE inhibitors (in the absence of contraindications to ACE inhibition) is the current criterion standard in the treatment of left ventricular dysfunction. ACE inhibitors have been shown to decrease mortality rates in both symptomatic and asymptomatic patients with left ventricular dysfunction and to reduce readmissions caused by heart failure. The absolute benefits are greater in patients with severe heart failure.
The dosage necessary for maximal benefit is debatable. However, authorities have generally accepted that maximizing ACE inhibitor therapy is important and should be accomplished in conjunction with other necessary therapies.
Enalapril (Vasotec)
Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. This agent helps control blood pressure and proteinuria. It decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance.
Enalapril has a favorable clinical effect when administered over a long period. It helps prevent potassium loss in distal tubules. Because the body conserves potassium, less oral potassium supplementation is needed.
Lisinopril (Prinivil, Zestril)
Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Ramipril (Altace)
Ramipril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Angiotensin II Receptor Blockers (ARBs)
Class Summary
Angiotensin receptor blockers are as effective as ACE inhibitors in the treatment of heart failure. Their adverse-effect profile is similar to that of ACE inhibitors with regard to renal insufficiency or hyperkalemia but they do not cause potentiation of bradykinin and therefore do not cause cough.
Valsartan (Diovan)
Valsartan is used in patients who cannot tolerate ACE inhibitors. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors. Valsartan does not affect the response to bradykinin and is less likely to be associated with cough and angioedema.
Losartan (Cozaar)
Losartan is an ARB that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema. It is used for patients unable to tolerate ACE inhibitors.
Candesartan (Atacand)
Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce more complete inhibition of renin-angiotensin system than ACE inhibitors, it does not affect response to bradykinin, and it is less likely to be associated with cough and angioedema. It is used in patients unable to tolerate ACE inhibitors.
Olmesartan (Benicar)
Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking binding of angiotensin II to the AT-1 receptor in vascular smooth muscle. Its action is independent of pathways for angiotensin II synthesis.
Angiotensin Receptor-Neprilysin Inhibitors (ARNi)
Class Summary
Neprilysin is responsible for degradation of atrial and brain natriuretic peptide. Inhibition of neprilysin results in increased natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP. Angiotensin II receptor type I inhibition reduces blood pressure and blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II.
Sacubitril/valsartan (Entresto)
Sacubitril/valsartan may be considered in place of ACE inhibitors for patients who remain symptomatic on optimal heart failure therapy. It is indicated to reduce the risk of cardiovascular death and hospitalization in chronic heart failure (CHF). Benefits are most clearly evident in adults with LVEF below normal.
Cardiovascular, Others
Class Summary
General guidelines for initiating beta-blocker therapy include treating all patients with left ventricular dysfunction except those who are acutely decompensated. Therapy should be initiated at low dosages, which should be increased gradually over several weeks. Patients' conditions may deteriorate over the short term, but they generally improve in the long term with continued therapy.
Carvedilol, bisoprolol, and metoprolol CR/XL are the only agents currently approved by the US Food and Drug Administration (FDA) for use in persons with heart failure. Carvedilol acts in 3 ways: as a beta-blocker, an alpha-blocker, and an antioxidant and may be more beneficial than metoprolol in heart failure.
Human B-type natriuretic peptide (BNP) is produced through recombinant DNA technology and has the same amino acid sequence as naturally occurring human BNP. Nesiritide is a human BNP.
Carvedilol (Coreg, Coreg CR)
Carvedilol blocks beta1-, alpha-, and beta2-adrenergic receptor sites, decreasing adrenergic-mediated myocyte damage.
Metoprolol (Lopressor, Toprol XL)
Metoprolol is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During intravenous administration of metoprolol, carefully monitor the patient's blood pressure, heart rate, and electrocardiogram.
Bisoprolol (Zebeta)
Bisoprolol is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions.
Nesiritide (Natrecor)
Nesiritide is a recombinant DNA form of human BNP that dilates veins and arteries. Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells. Binding to receptor causes increase in cGMP, which serves as second messenger to dilate veins and arteries. This, in turn, leads to smooth muscle relaxation and vasodilation. Venous and arterial dilation results in decreased preload and afterload and reductions in pulmonary capillary wedge pressure. Human BNP is indicated for temporary use in patients with acutely decompensated CHF.
Human BNP has additional beneficial effects for heart failure patients. Neurohormonal effects on the rennin-angiotensin-aldosterone system (RAAS) result in reductions in plasma norepinephrine and a trend toward a decrease in aldosterone levels. Renal effects include diuresis and natriuresis with at least preservation, if not an increase, in renal blood flow and glomerular filtration rate.
Aldosterone Antagonists, Selective
Class Summary
Spironolactone is complementary to standard therapy in modulating the renin-angiotensin-aldosterone system (RAAS) because aldosterone levels remain elevated despite ACE inhibitor therapy. Spironolactone is currently indicated for treating patients with mild-to-severe heart failure (NYHA class II-IV) in addition to ACE inhibitors, beta-blockers, diuretics, and digoxin.
Aldosterone antagonist therapy should be used with great caution in patients with serum potassium levels greater than 5 mmol/L or those with serum creatinine levels greater than 2.5 mg/dL. Whether mortality is more significantly lowered by reduction and reversal of fibrosis or by maintenance of potassium/magnesium tissue levels is unclear.
Eplerenone (Inspra)
Eplerenone selectively blocks aldosterone at the mineralocorticoid receptors in epithelial (eg, kidney) and nonepithelial (eg, heart, blood vessels, and brain) tissues; thus, it decreases blood pressure and sodium reabsorption. This agent is indicated to improve survival for congestive heart failure or left ventricular dysfunction following acute myocardial infarction (MI). It is a more specific mineralocorticoid antagonist than spironolactone, and thus avoids the gynecomastia, breast pain, and menstrual disturbances common in patients on spironolactone.
Spironolactone (Aldactone)
Spironolactone is indicated for management of edema resulting from excessive aldosterone excretion. It competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. Therapy may be switched to eplerenone in the presence of gynecomastia.
Antidysrhythmics, III
Class Summary
Antiarrhythmics are useful in patients with supraventricular and nonsustained ventricular tachycardias. Not all antiarrhythmics are considered safe in patients with structural heart disease. The class III antiarrhythmics amiodarone and dofetilide are favored in these patients for the treatment of supraventricular and ventricular dysrhythmias.
Amiodarone (Cordarone)
Amiodarone is a class III antiarrhythmic agent (K-channel blocker) with class I activity that may inhibit atrioventricular conduction and sinus node function. It prolongs the action potential and refractory period in myocardium and inhibits adrenergic stimulation.
In patients with recent myocardial infarction and congestive heart failure, amiodarone reduces sudden cardiac death but is inferior compared to ICDs.
For patients with heart failure presumed to be resultant from atrial fibrillation, rhythm control should be attempted. Amiodarone is commonly initiated, with cardioversion attempted 1 month later. Amiodarone is among the most effective antiarrhythmic agents for suppression of atrial fibrillation. In patients with systolic heart failure and atrial fibrillation, rhythm control does not improve mortality, hospitalization for heart failure exacerbation, or stroke as compared to rate control. [Roy D, Talajic M, Nattel S, et al, for the Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008 Jun 19. 358 (25):2667-77.]
Monitoring of pulmonary, thyroid, and liver toxicity while patients are on amiodarone therapy is advised.
Dofetilide (Tikosyn)
Dofetilide is the prototype of a "pure" class III agent. It has been approved by the US Food and Drug Administration (FDA) for maintenance of sinus rhythm after conversion from atrial fibrillation or atrial flutter lasting longer than 1 week. It is also indicated for conversion of atrial fibrillation and atrial flutter to normal sinus rhythm. If patients do not convert within 24 hours of initiation of therapy, electrical cardioversion should be considered.
Torsade de pointes is the only complicating arrhythmia showing dose-response relationship. The prevalence with supraventricular arrhythmia is 0.8%. Majority of torsade de pointes episodes occur within first 3 days of therapy.
Dofetilide has no effect on cardiac output, cardiac index, stroke volume index, or systemic vascular resistance in patients with ventricular tachycardia, mild-to-moderate heart failure, angina, and either normal or reduced left ventricular ejection fraction (LVEF). It does not affect blood pressure.
Dofetilide blocks delayed rectifier current (IKr) and prolongs action potential duration; indeed, even at higher magnitudes, it has no effect upon other depolarizing potassium currents (IKs and IKl). It terminates induced re-entrant tachyarrhythmias (atrial fibrillation/flutter and ventricular tachycardia) and prevents their re-induction. At clinically prescribed concentrations, it has no effect on sodium channels, which are associated with class I effects. Furthermore, no effect is noted on alpha- or beta-adrenergic receptors.
Dofetilide must be initiated with continuous ECG monitoring and monitoring must be continued for more than 12 hours after conversion. Dose must be individualized according to creatinine clearance (CrCl) and QTc (use QT interval if heart rate < 60/min). There is no information on use of this drug for heart rates less than 50 beats per minute.
Diuretics, Loop
Class Summary
Diuretics are reserved for congestive states. They are not indicated for patients with functional restriction in the absence of edema/congestion.
Patients can effectively adjust their diuretic use by weighing themselves at home. If patients have a 3- to 5-lb weight gain in 1-7 days, they should be advised to double their diuretic dose and potassium supplement for 1 day. Additional treatment should be based on the effectiveness of this increased dose to reduce weight or symptoms. Agents such as metolazone, hydrochlorothiazide, and acetazolamide may be used to augment effects of loop diuretics.
Furosemide (Lasix)
Furosemide increases excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. The bioavailability of oral furosemide is 50%. If a switch is made from IV to oral administration, an equivalent oral dose should be used. Doses vary depending on the patient's clinical condition.
Bumetanide
Bumetanide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle. This agent does not appear to act in the distal renal tubule.
Torsemide (Demadex)
Torsemide is well-absorbed, with a peak plasma concentration within 1 hour. Oral bioavailability does not differ between patients with CHF and normal patients (80-90%).
The bioavailability of furosemide is aoout 50%, but it is highly variable (10-90%). In patients with severe edema that may impair absorption, the furosemide effect may be limited, and therapy should be switched to torsemide.
Bumetanide has an oral bioavailability of 80-100%. Torsemide is considered superior to furosemide and bumetanide: Its bioavailability is superior to that of furosemide, and it has a longer half-life than bumetanide.
Ethacrynic acid (Edecrin)
Ethacrynic acid increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. This agent is used only in refractory cases. Continuous IV infusion is preferable in many cases. It is indicated for temporary treatment of edema associated with heart failure when greater diuretic potential is needed. It is useful for patients who have a true sulfonamide allergy.
Vasodilators
Class Summary
Preload reduction with venodilators is thought to be helpful in acute decompensated heart failure by reducing congestions and minimizing cardiac oxygen demand. Afterload reduction is also thought to be helpful in some patients with acute decompensated heart failure by decreasing myocardial oxygen demand and improving forward flow.
Sublingual nitroglycerin spray, nitropaste, and IV nitroglycerin have been advocated in the treatment of pulmonary edema secondary to CHF. Morphine also has significant vasodilatory effects and can be useful.
Hydralazine
Hydralazine decreases systemic resistance through direct vasodilation of arterioles.
Isosorbide dinitrate and hydralazine (BiDil)
This product is a fixed-dose combination of isosorbide dinitrate (20 mg/tab), a vasodilator with effects on both arteries and veins, and hydralazine (37.5 mg/tab), a predominantly arterial vasodilator. It is indicated for heart failure in black patients.
Nitroglycerin topical (Nitro-Bid, Nitro-Dur, Minitran)
Nitroglycerin causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate (cGMP) production, resulting in a decrease in blood pressure.
Ivabradine (Corlanor)
In patients with systolic heart failure with an LVEF below 35%, who are in sinus rhythm, have a resting heart rate more than 70 beats per minute, and are on maximally tolerated doses of beta-blockers or who were intolerant to beta blockers, ivabradine reduces cardiovascular death and hospital admission for worsened heart failure.
Inotropic Agents
Class Summary
Long-term use of the phosphodiesterase inhibitor milrinone has deleterious effects on survival in patients with heart failure. Improvement of CHF symptoms occurs as the trade-off for this increase in mortality. Inotropic agents are reserved for patients who need hemodynamic-directed treatment during acute decompensation, those refractory to maximal standard therapy, as palliation for end-stage heart failure, or as a bridge to transplantation for appropriate candidates. Milrinone may have an advantage over dobutamine in that it can be used for acute inotropic support during introduction of beta-blocker therapy, particularly in those who are beta-blocker intolerant due to the myocardial depressant effects. [] 170]
Digoxin therapy for heart failure has no benefit on mortality rates. However, it does improve NYHA functional class, hemodynamics, symptoms, exercise capacity, and quality of life and reduces hospitalizations for heart failure. Patients with worse NYHA functional class and lower left ventricular ejection fraction benefit most from digoxin therapy.
Milrinone
Milrinone is a phosphodiesterase III inhibitor that prevents degradation of cAMP, ultimately leading to increased myocardial contraction and lusitropy, decreased pulmonary vascular resistance, and reduced afterload. It differs in mode of action from both digitalis glycosides and catecholamines. This agent is used for the short-term management of acute decompensated heart failure.
Dobutamine
In patients with cardiogenic shock/decompensated heart failure due to myocardial dysfunction, dobutamine is a beta-agonist that may be acutely used to increase cardiac output. In those with low-flow heart failure, chronic dobutamine infusion may be considered in those awaiting transplant or for those who are not candidates for advanced therapies (transplant, ventricular assist device).
Note that chronic infusion may be associated with an increased mortality risk due to ventricular arrhythmias.
Digoxin (Lanoxin)
Digoxin is a cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. It acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
Anticoagulants, Cardiovascular
Class Summary
The use of anticoagulants is restricted to patients in atrial fibrillation, with artificial valves, and with known mural thrombus. Some data support their use in patients with low ejection fractions.
Warfarin (Coumadin)
Warfarin interferes with the hepatic synthesis of vitamin K–dependent coagulation factors. Tailor the dose to maintain the International Normalized Ratio (INR) in the range of 2-3.
Tables
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Blood Pressure Control
- ACE Inhibitors and ARBs
- Beta Blockers
- Aldosterone Antagonists
- Cardiac Glycosides
- Diuretics
- Antiarrhythmics
- Vasodilators
- Human B-Type Natriuretic Peptide
- Inotropic Agents
- Anticoagulation
- Left Ventricular Assist Devices
- Cardiac Resynchronization Therapy (Biventricular Pacing)
- Automatic Implantable Cardioverter-Defibrillators
- Heart Transplantation
- Diet and Activity
- Cardiac Rehabilitation
- Investigational Therapy for Heart Failure
- Consultations
- Show All
- Medication
- Questions & Answers
- References
