Congestive heart failure pharmacotherapy

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Systolic Dysfunction
Diastolic Dysfunction
HFpEF
HFrEF

Causes

Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Cardiac MRI

Echocardiography

Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies

Treatment

Invasive Hemodynamic Monitoring

Medical Therapy:

Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Nitrates
Hydralazine
Positive Inotropics
Anticoagulants
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
Ultrafiltration
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 pharmacotherapy On the Web

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Risk calculators and risk factors for Congestive heart failure pharmacotherapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Seyedmahdi Pahlavani, M.D. [3]

Overview

Management of patients with heart failure reduced ejection fraction (HFrEF)

Abbreviations: ACE-I: Angiotensin-converting enzyme inhibitor; ARNI: Angiotensin receptor-neprilysin inhibitor; CRT-D: cardiac resynchronization therapy with defibrillator  ; CRT-P: cardiac resynchronization therapy with pacemaker; ICD: Implantable cardioverter-defibrillator; HFrEF: Heart failure with reduced ejection fractio;

 
 
 
 
 
 
 
 
Management of HFrEF
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Class I)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LVEF ≤35% and QRS <130 ms
 
 
 
 
LVEF >35% or device

therapy not indicated

or inappropriate
 
 
 
 
Sinus rhythm and LVEF ≤35% and QRS ≥130 ms
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ICD implantation
 
 
 
 
If symptoms persist, consider therapies (class II)
 
 
 
 
CRT-D/-P
  • QRS ≥150 ms (Class I)
  • QRS 130-149 ms (Class IIa)
  •  
     
     
     
     
     
     
     
     
     
     
    The above table adopted from 2021 ESC Guideline

    [1]

    Congestive heart failure treatment summary based on 2021 AHA/ACC Guideline

    [2]

    Pathophysiology Treatment
    Renin-angiotensin-aldosterone system ARNIs/ACEIs/ARBs, aldosterone antagonist
    Sympathetic nervous system Beta-blockers
    Natriuretic and other vasodilator peptides Neprilysin inhibitor (ARNI)
    Sodium-glucose cotransporter-2 SGLT2 inhibitors
    Balanced vasodilation and oxidative stress modulation Hydralazine/Isosorbide dinitrate
    Elevated heart rate Betablocker, Ivabradine
    Guanylyl cyclase Soluble guanylyl cyclase stimulator
    Relief of congestion Diuretic
    Ventricul;ar arrhythmia Implantable cardioverter defibrilator
    Ventricular dyssynchrony due to conduction abnormalities Cardiac resynchronization therapy
    Mitral regurgitation Surgical or percutaneous Mitral repair
    Reduced aerobic capacity Aerobic exercise training
    The above table adopted from 2021 AHA/ACC Guideline

    Treatment Algorithm for Guideline-Directed Medical Therapy Including Novel Therapies

     
     
     
     
     
     
     
     
     
    Heart failure reduced EF, stage C, treatment
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    ARNI, ACEI, ARB
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    For patients with eGFR≥ 30 mL/min/1.73m² or creatinine≤ 2.5 mg/dL in males or ≤2 mg/dL in females or K≤ 5 mEq/L, NYHA 2-4
     
    For patients with eGFR criteria, NYHA 2-4
     
    For patients with persistent volume overload, NYHA 2-4
     
    For symptomatic black patients despite receiving ARNI, betablocker,aldosterone antagonist, SGLT2 inhibitor, NYHA 3-4
     
    For patients with resting HR>70/min despite maximum tolerated betablocker dose, sinus rhythm, NYHA 2-3
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Add
     
     
    Add
     
    Titrate
     
    Add
     
    Add
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Aldosterone antagonist
     
     
    SGLT2 inhibitor
     
    Diuretic agents
     
    Hydralazine + Isosorbide dinitrate
     
    Ivabradine
     
     
    The above algorithm adopted from 2021 AHA/ACC Guideline










     
     
     
    ACEI, ARB
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Starting in patient if ARNI is not accessible
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Dosage initiation based on indication
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Increasing dose every 2 weeks until achieving target dose or maximum tolerance and monitoring of blood pressure, renal function, potassium after initiation and during titration
     
     
     


     
     
     
    ARNI
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Initiation after 36 hours of discontinuing ACEI, if the patient is on ACEI
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Dosage initiation based on indication
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    24/26 mg twice daily if the patient is taking enalapril≤ 10 mg/day or valsartan≤ 160 mg/day
     
     
     
    49/51 mg twice daily if the patient is taking enalapril> 10 mg/day or valsartan > 160 mg/day
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    In 2 weeks assessment about tolerance, blood pressure, electrolytes, renal function and dosage titration to target of 97/103 mg twice daily
     
     
     
     
     
     
     
     





     
     
     
    Diuretics
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Initiation loop diuretic dose based on renal function, previous use of diuretics
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Titration dose until recovery of congestion, reducing dose in concomitant administration of ACEI, ARB, ARNI, monitoring blood pressure, renal function, electrolytes after initiation and during titration dose
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    In high dose of loop diuterics (80 mg furosemide twice daily), Considering other type of loop diuretics or adding thiazide to loop diuretic by monitoring of blood pressure, renal function, electrolytes after initiation dose or during titration
     
     
     


     
     
     
    SGLT2 inhibitor
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Dosage initiation based on indication
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Initiation dapaglifelozin in eGFR≥ 30 mL/min/1.73 m², and empagliflozin in eGFR≥ 20 mL/ min/1.73 m²
     
     
     







     
     
     
    Betablocker
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Dosage initiation based on indication
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Dosage titration every two weeks until achieving target dose or maximum tolerance, monitoring heart rate , blood pressure after initiation and during titration
     
     
     


     
     
     
    Aldosterone antagonist
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Dosage initiation based on indication
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Increase dose every 2 weeks up to maximum dose or achieving tolerated dose, monitoring electrolytes and renal function at 2-3 days following initiation then 7 days after initiation or titration, then monthly for 3 months and every 3 months afterward, clinical status monitoring
     
     
     


     
     
     
    Hydralazine, isosorbide dinitrate
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Increase dose every 2 weeks until target dose or achieving tolerated dose with monitoring of blood pressure
     
     
     



    Sacubitril/Valsartan Ivabradine SGLT2 Inhibitors
    Contraindications Contraindications Contraindications
    Causions
    • Renal impairment:
      Mild-to-moderate (eGFR 30-59 mL/ min/1.73 m2): no starting dose adjustment required
    • Severe (eGFR <30 mL/min/ 1.73 m2):
      Reduce starting dose to 24/26 mg twice daily,
      Double the dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily, as tolerated
    • Hepatic impairment:
      Mild (Child-Pugh A): no starting dose adjustment required
      Moderate (Child-Pugh B):
      Reduce starting dose to 24/26 mg twice daily
      Double the dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily, as tolerated
    • Renal artery stenosis
    • Systolic blood pressure <100 mm Hg
    • Volume depletion
    Causions Causions

    For prevention of ketoacidosis in patients with diabetes:

    erythema, or swelling in the genital or perineal area, along with fever or malaise

    The above table adopted from 2021 AHA/ACC Guideline[2]



     
     
     
    Ivabradine
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Given Betablocker by maximum tolerable dose, sinus rhythm on ECG
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Starting dose
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Age ≥ 75 years, 2.5 mg twice daily with food
     
     
     
    Age <75 years, 5 mg twice daily with food
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Evaluation of heart rate in 2-4 weeks
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Heart rate < 50 beats /min or symptoms of bradycardia
     
    Heart rate 50-60 beats/ min
     
    Heart rate>60 beats /min
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Reduced dose 2.5 mg twice daily with food, or discontinued if already on 2.5 mg twice daily
     
    Maintaing current dose with monitoring heart rate
     
    Increased dose by 2.5 mg twice daily until maximum dose of 7.5 mg twice daily, monitoring heart rate
     

    References

    1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland J, Coats A, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam C, Lyon AR, McMurray J, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano G, Ruschitzka F, Kathrine Skibelund A (September 2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check |pmid= value (help). Vancouver style error: initials (help)
    2. 2.0 2.1 Bozkurt B, Hershberger RE, Butler J, Grady KL, Heidenreich PA, Isler ML, Kirklin JK, Weintraub WS (April 2021). "2021 ACC/AHA Key Data Elements and Definitions for Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Heart Failure)". Circ Cardiovasc Qual Outcomes. 14 (4): e000102. doi:10.1161/HCQ.0000000000000102. PMC 8059763 Check |pmc= value (help). PMID 33755495 Check |pmid= value (help).

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