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: Sara Zand, M.D.[2] Rim Halaby, M.D. [3]


Pharmacotherapy is the mainstay of therapy for heart failure with reduced ejection fraction (HFrEF) and should be initiated before considering device therapy.Three major goals of therapy for patients with HFrEF including reduction in mortality, prevention of hospitalization due to worsening HF, and improvement in clinical status. Suppression of renin-angiotensin-aldosterone (RAAS) and sympathetic nervous systems with angiotensin-converting enzyme inhibitors (ACE-I) or an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blockers, and mineralocorticoid receptor antagonists (MRA) have been shown to improve survival, reducing the risk of HF hospitalizations, and reducing symptoms in patients with HFrEF. ACE-I/ARNI, a beta-blocker, and an MRA are recommended as cornerstone therapies for these patients, unless the drugs are not tolerated or contraindicated. 2021 ESC Guideline recommends the use of ARNI as a replacement for ACE-I in symptomatic patients with ACE-I, beta-blocker, and MRA therapies. ARNI may be considered as a first-line therapy instead of an ACE-I. Angiotensin-receptor blockers (ARBs) are recommended in patients intolerant to ACEI or ARNI. The sodium-glucose co-transporter 2 (SGLT2) inhibitors including dapagliflozin and empagliflozin added to therapy with ACE-I/ ARNI/ beta-blocker/ MRA to reduce the risk of cardiovascular death and worsening HF in patients with HFrEF.

Starting and target doses of medications and novel therapies for heart failure

Betablockers Starting dose Target dose
Bisoprolol 1.25 mg once daily 10 mg once daily
Carvedilol 3.125 mg twice daily 25 mg twice daily for weight <85 kg and 50 mg

twice daily for weight≥ 85 kg

Metoprolol succinate 12.5–25 mg daily 200 mg daily
Sacubitril/valsartan 24/26 mg–49/51 mg twice daily 97/103 mg twice daily
Captopril 6.25 mg 3× daily 50 mg 3× daily
Enalapril 2.5 mg twice daily 10–20 mg twice daily
Lisinopril 2.5–5 mg daily 20–40 mg daily
Ramipril 1.25 mg daily 10 mg daily
Candesartan 4–8 mg daily 32 mg daily
Losartan 25–50 mg daily 150 mg daily
Valsartan 40 mg twice daily 160 mg twice daily
Aldosterone antagonists
Eplerenone 25 mg daily 50 mg daily
Spironolactone 12.5–25 mg daily 25–50 mg daily
SGL2 ihibitors
Dapagliflozin 10 mg daily 10 mg daily 10 mg daily
Empagliflozin 10 mg daily 10 mg daily
Hydralazine 25 mg 3× daily 75 mg 3× daily
Isosorbide dinitrate 20 mg 3× daily 40 mg 3× daily
Fixed-dose combination isosorbide dinitrate/hydralazine 20 mg/37.5 mg (1 tab) 3× daily 2 tabs 3× daily
Ivabradine 2.5–5 mg twice daily Titrate to heart rate 50–60 beats/min, Maximum dose 7.5 mg twice daily
The above table adopted from 2021 AHA/ACC Guideline


Drugs recommended in all patients with heart failure with reduced ejection fraction

Medications indicated in patients with New York Heart Association (NYHA class II–IV) heart failure with reduced ejection fraction (LVEF ≤ 40%)

Recommendations for HFrEF and NYHA class II–IV
(Class I, Level of Evidence A):

ACE-I is recommended for patients with HFrEF to reduce the risk of HF hospitalization and death
Beta-blocker is recommended for patients with stable HFrEF to reduce the risk of HF hospitalization and death
MRA (Mineralocorticoid receptor antagonist) is recommended for patients with HFrEF to reduce the risk of HF hospitalization and death
Dapagliflozin or empagliflozin are recommended for patients with HFrEF to reduce the risk of HF hospitalization and death

(Class I, Level of Evidence B):

Sacubitril/valsartan is recommended as a replacement for an ACE-I in patients with HFrEF to reduce the risk of HF hospitalization and death

The above table adopted from 2021 ESC Guideline


Angiotensin-converting enzyme inhibitors


MRA or Mineralocorticoid receptor antagonists

Angiotensin receptor-neprilysin inhibitor

and a reduction in the decline in eGFR [7]as well as a reduced rate of hyperkalemia[8].

Sodium-glucose co-transporter 2 inhibitors

  • A small reversible reduction in eGFR following initiation

Medications with reducing mortality in heart failure reduced EF

Medications with reducing hospitalization in heart failure reduced EF

Other medications in HFrEF in patients with NYHA 2-4

Recommendations for heart failure with reduced ejection fraction and NYHA 2-4
Loop diuretics (Class I, Level of Evidence C):

Loop diuretics are recommended in patients with HFrEF with signs and/or symptoms of congestion to improve HF symptoms, exercise capacity, and reduce HF hospitalizations

ARB (Class I, Level of Evidence B):

ARB is recommended in symptomatic patients to reduce the risk of HF hospitalization and cardiovascular death for whom unable to tolerate an ACE-I or ARNI (patients should also receive a beta-blocker and MRA)

If-channel inhibitor :(Class IIa, Level of Evidence B) :

Ivabradine should be considered in symptomatic patients with LVEF ≤35%, sinus rhythm on ECG and a resting heart rate≥ 70 b.p.m despite treatment with maximum tolerated beta-blocker, ACE-I/(or ARNI), and an MRA, to reduce the risk of HF hospitalization and cardiovascular death

If-channel inhibitor : (Class IIa, Level of Evidence C)

Ivabradine should be considered in symptomatic patients with LVEF≤ 35%, in sinus rhythm and a resting heart rate≥ 70 b.p.m. when can not tolerate or have contraindications for a beta-blocker, for reduction the risk of HF hospitalization and cardiovascular death. Patients should also receive an ACE-I (or ARNI) and MRA

Soluble guanylate cyclase receptor stimulator: (Class IIb, Level of Evidence B)

Vericiguat may be considered in patients in NYHA class II-IV with worsening HF despite therapy with an ACE-I (or ARNI), a beta-blocker and MRA to reduce the risk of cardiovascular death or HF hospitalization

Hydralazine, isosorbide dinitrate : (Class IIa, Level of Evidence B)

Hydralazine and isosorbide dinitrate should be considered in black patients with LVEF ≤35% or with an LVEF<45% combined with a dilated left ventricle in NYHA class III-IV despite therapy with an ACE-I (or ARNI), a beta-blocker and an MRA to reduce the risk of HF hospitalization and death.1

Hydralazine, isosorbide dinitrate (Class IIb, Level of Evidence B):

Hydralazine and isosorbide dinitrate may be considered in patients with symptomatic HFrEF who unable to tolerate any of an ACE-I, an ARB, or ARNI (or they are contraindicated) to reduce the risk of death

Digoxin: (ClassIIb, Level of Evidence B)

Digoxin may be considered in patients with symptomatic HFrEF in sinus rhythm despite treating with an ACE-I (or ARNI), a beta- blocker and an MRA, to reduce the risk of hospitalization (both all-cause and HF hospitalizations)

The above table adopted from 2021 ESC Guideline



Angiotensin II type I receptor blockers

If -channel inhibitor

Combination of hydralazine and isosorbide dinitrate


Soluble guanylate cyclase receptor stimulator

Cardiac myosin activator

Management of chronic heart failure

Serial clinical evaluation , titration of Medications

Intensification 2-4 months, (1-4 weeks cycles)

  • In the presence of volume overload, adjusting diuretic dose and reevaluation in 1-2 weeks
  • In the setting of stable euvolumic status, medications initiation, increase, switch dose and follow-up in 1-2 weeks and checking basic metabolites panel, repeating cycles until no change in clinical status and reached appropriate titration

Assessment of response to medications and cardiac remodeling

Lack of response, instability

Assessment of response to medications


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