Congestive heart failure chronic pharmacotherapy

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Congestive Heart Failure Microchapters


Patient Information


Historical Perspective



Systolic Dysfunction
Diastolic Dysfunction


Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings


Chest X Ray

Cardiac MRI


Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies


Invasive Hemodynamic Monitoring

Medical Therapy:

Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Positive Inotropics
Angiotensin Receptor-Neprilysin Inhibitor
Antiarrhythmic Drugs
Nutritional Supplements
Hormonal Therapies
Drugs to Avoid
Drug Interactions
Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure chronic pharmacotherapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


Ongoing Trials at Clinical

US National Guidelines Clearinghouse

NICE Guidance

FDA on Congestive heart failure chronic pharmacotherapy

CDC on Congestive heart failure chronic pharmacotherapy

Congestive heart failure chronic pharmacotherapy in the news

Blogs on Congestive heart failure chronic pharmacotherapy

Directions to Hospitals Treating Congestive heart failure chronic pharmacotherapy

Risk calculators and risk factors for Congestive heart failure chronic pharmacotherapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]


There are several goals in the chronic management of systolic heart failure. The management of diastolic heart failure is discussed elsewhere. One goal of therapy is to improve the patient's symptoms, exercise tolerance and quality of life. Diuretics, along with regular assessment of the patient's weight, minimizes fluid accumulation and the accompanying symptoms of dyspnea and orthopnea. Another goal is to reduce hospitalization and mortality. To achieve the second goal, patients with chronic heart failure should be administered an ACE inhibitor (or ARB if they are ACE intolerant) and a beta blocker. If the patient remains symptomatic, additional therapy may include an aldosterone antagonist.

Diuresis: First Step in the Management of Heart Failure

The treatment of chronic heart failure often begins with the administration of diuretics, particularly if the patient has signs or symptoms of volume overload. While increased left ventricular volume increases contractility to a point, if the heart is filled beyond that point, its contractility diminishes (the patient "falls of the Staring curve"). Diuretics can reduce volume overload and reduce shortness of breath and edema. There are three kinds of diuretics, loop diuretics, thiazides and potassium-sparing diuretics. Diuretics rapidly improve the symptoms of heart failure (within hours to days). Diuretics reduce excess volume that accumulates with heart failure and decrease pulmonary edema that causes symptoms of dyspnea and orthopnea[1]. Lasix 20 to 40 mg PO daily is a conventional starting dose, but in some patients, torsemide may be a better choice due to its more predictable absorption. Once a day dosing of a given diuretic is preferred to twice a day dosing at a lower dose. A rise in BUN and Cr may reflect a reduction in renal perfusion, and further diuresis should only be undertaken with careful monitoring of renal function. The patient should weigh themselves each morning at the same time on the same scale, and the diuretic dosing should be adjusted to maintain a constant weight. Given the risk of hypokalemia or hyperkalemia, the blood level of electrolyes should be checked regularly.

  • Simultaneous With Initiating Diuresis

ACE Inhibition and Angiotensin Receptor Blockade: Second Step in the Management of Heart Failure

After diuretics are started or at the same time they are started, an ACE inhibitor can be initiated [6]. This includes a large group of drugs, such as Enalapril (Vasotec/Renitec), Ramipril (Altace/Tritace/Ramace/Ramiwin), Quinapril (Accupril), Perindopril (Coversyl/Aceon), Lisinopril (Lisodur/Lopril/Novatec/Prinivil/Zestril) and Benazepril (Lotensin). They can improve symptoms and prognosis of heart failure in several ways including afterload reduction and favorable ventricular remodeling. Potential side effects of ACE inhibitors include dry cough and angioedema. Patients with bilateral renal artery stenosis or severe renal impairment are not appropriate for angiotensin converting enzyme inhibitor (ACEI).

During or after the initiation of diuresis, one could start, for example, lisinopril 5 mg Q day. Every 1 - 2 weeks, the dose would be escalated to achieve a target dose of 15 to 20 mg Q day. An ACE inhibitor is initiated before a beta blocker because an ACE inhibitor achieves its hemodynamic effect more rapidly, and is less likely to cause a decline in hemodynamics. Although there is some data to suggest that aspirin blunts the hemodynamic effect of ACE inhibitors, there is no data to suggest that aspirin reduces the clinical efficacy of ACE inhibitors in heart failure patients. Aspirin should be administered to patients with ischemic heart disease, but not to patients without it.

If a patient cannot tolerate a an ACE inhibitor (develops a cough), then an Angiotensin II receptor blocker can be administered in its place. Angiotensin II receptor antagonists block the activation of angiotensin II AT1 receptors. Blockade of AT1 receptors directly causes vasodilation, reduces secretion of vasopressin, and reduces production / secretion of aldosterone. Because angiotensin II receptor antagonists do not inhibit the breakdown of bradykinin or other kinins, they are rarely associated with the persistent dry cough and/or angioedema, side effects which limit ACE inhibitor therapy. Commonly administered agents in the management of heart failure include Candesartan, Valsartan, Telmisartan, Losartan, Irbesartan, and Olmesartan. The effectiveness of switching to an ARB from and ACE inhibitor was demonstrated for candesartan in the CHARM Alternative trial [7].

In general, ARBs are as effective or slightly less effective than ACE inhibitors in the treatment of congestive heart failure.[8][9] It is a class 2a recommendation to substitute an ARB as an alternative to ACE inhibitors if the patient is already taking an ARB for another indication.[10]

The efficacy of adding an ARB to an ACE inhibitor was assessed in the CHARM Added trial[11]. While there was a reduction in the composite primary endpoint in the study, there was no reduction in mortality. Furthermore, the VALIANT trial demonstrated that an ARB should not be added to an ACE inhibitor in the post MI setting.

These negative results for adding ARBs on top of an ACE inhibitor in the post MI setting are in contrast to the results of the EMPHASIS HF trial which demonstrated that the addition of eplerenone (an aldosterone antagonist) to ACE inhibition improved clinical outcomes including mortality among patients with class II or III heart failure with a reduced LVEF.[12] Thus, based upon the mortality benefit observed in the EMPHASIS HF trial, an aldosterone antagonist rather than and ARB should be added to an ACE inhibitor in patients with

"Triple therapy", the combined use of an ACE inhibitor, an ARB and an aldosterone antagonist is a relative contraindication.

Beta blockers: Third Step in the Management of Heart Failure

Beta blockers reduce the heart rate which lowers the myocardial energy expenditure. They also prolong diastolic filling and lengthen the period of coronary perfusion. Beta blockers can also decrease the toxicity of catecholamines on the myocardium.

Once you have achieved a stable dose of a diuretic and an ACE inhibitor, then one of the three beta blockers that have been associated with improved survival (carvedilol, metoprolol succinate or bisoprolol) can be added and the dose titrated based upon the patient's tolerance. You should avoid beta-blockers with intrinsic sympathomimetic activity (pindolol or acebutolol). It should be noted that the 35% reduction in one year mortality observed in meta-analyses of beta-blockers in heart failure was when these drugs were added to ACE inhibitors[13]. There are no direct comparisons of the various beta-blockers, but some data does suggest that carvedilol may improve LVEF more than the others, but it may not be as well tolerated due to its vasodilatory properties. If the patient has been over diuresed, they may not tolerate the addition of a beta blocker.

Relative contraindications to beta-blocker administration include the following:

Given the potential for hemodynamic decompensation, the initiation of beta-blockers is best undertaken by an individual or center specializing in heart failure management. The patient should be aware of potential side effects, and should be aware that it may take one to three months for the beta-blockers to improve heart failure symptoms. Therapy is initiated with very low doses, and the dose of the beta-blocker should be doubled every two weeks until the target dose is achieved or symptoms prevent further dose escalation.

  • Carvedilol: Initial dose 3.125 mg twice daily, target dose 25 to 50 mg twice daily
  • Metoprolol succinate: Initial dose 12.5 mg daily, target dose 200 mg daily
  • Bisoprolol: Initial dose 1.25 mg daily, target dose 5 to 10 mg daily

Weight gain or peripheral edema that is not responsive to diuresis may require a reduction in the dose of beta-blockers.

Aldosterone Antagonism: Fourth Step in the Management of Heart Failure

An aldosterone antagonist can be added to the regimen of 'select' patients. These selected patients include:

A requirement for aldosterone antagonist is that the patient's renal function and potassium can be carefully monitored. Eplerenone has fewer endocrine side effects (1%) than spironolactone (10%), but is more costly. A reasonable strategy is to initiate therapy with spironolactone at a dose of 25 to 50 mg daily, and then switch to eplerenone at a dose of 25 to 50 mg daily if endocrine side effects develop.

Risk Factors for the Development of Hyperkalemia on an Aldosterone Antagonist

The Combination of Hydralazine and a Nitrate: Fifth step in the Management of Heart Failure

The combination of hydralazine and a nitrate (particularly among black patients) can be added if the patient continues to have symptoms on a diuretic, ACE inhibitor (or ARB in the intolerant patient) and a beta blocker. The initial dose is isosorbide dinitrate 20 mg three times a day along with hydralazine 25 mg three times a day. The dose(s) can be increased every 2 to 4 weeks to a target dose of isosorbide dinitrate 40 mg three times a day and hydralazine 75 mg three times a day.

Digoxin: Sixth step in the Management of Heart Failure

Digitalis can strengthen the contractility of the heart and can also be useful to achieve rate control in patients with heart failure who also have atrial fibrillation. In the DIG trial, digoxin reduced the rate of re-hospitalization but did not improve mortality among all patients enrolled in the trial.[14] However, in a retrospective analysis, mortality was reduced in male patients who had digoxin levels between 0.5 and 0.8 ng/mL and was increased in male patients with digoxin levels > 1.2 ng/ml.[15] A similar trend was observed among women patients: there was a trend towards lower mortality at digoxin concentrations between 0.5 to 0.9 ng/ml, but significantly higher mortality at digoxin concentrations > 1.2 ng/ml.[16]

Digoxin should not be used as primary therapy for congestive heart failure. The administration of digoxin is reasonable in patients with NYHA class II-IV heart failure symptoms who have an LVEF of < 40% despite treatment with diuretics, angiotensin-converting enzyme inhibitors, beta blockers, and an aldosterone antagonist. Small doses of 0.125 mg per day of digoxin are often effective in maintaining a serum digoxin level between 0.5 and 0.8 ng/ml.

Shown below is an image that summarizes the steps in the chronic management of patients with heart failure.
Management of chronic heart failure


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