Heart Failure Treatment at a Glance

First-Line

ARNI (sacubitril/valsartan [Entresto])

• Patients with Class II to III HF symptoms, to reduce morbidity and mortality.¹
• Also consider for patients with prior or current symptoms and EF 41% to 49% (US).¹

Comments:

• May start at same time as beta-blocker, aldosterone antagonist, and/or SGLT2 inhibitor, but individualize sequencing and titration based on symptoms, functional status, vitals, kidney function, electrolytes, comorbidities, and follow-up.¹ For tips on initiating therapy based on kidney function, see our toolbox, Improving Heart Failure Care.
• Do not use with an ACEI or ARB, or within 36 hours of the last dose of an ACEI, or in patients with a history angioedema.^4,5
• Pivotal trial excluded patients with symptomatic hypotension, SBP <100 mm Hg, serum potassium
  >5.2 mEq (mmol)/L, or eGFR <30 mL/min/1.73m².⁶
• Prevents CV death or HF hospitalization in 1 in 21 patients treated for two years vs an ACEI, but also causes symptomatic hypotension in 1 in 21 patients [Evidence level A-1].⁶
• Efficacy in early post-MI patients is unknown.¹
• Dosed twice daily.^4,5

ACEI

• Alternative for patients in whom an ARNI can’t be used, to reduce morbidity and mortality.¹
• Patients with HF or EF <40% post-MI (Canada).²

Comments:

• For patients already tolerating an ACEI, consider switching to an ARNI to further reduce morbidity and mortality.¹ (Canada: switch patients who remain symptomatic or who have a HF hospitalization.²)
• Wait at least 36 hours after stopping the ACEI if switching to Entresto,to reduce the risk of angioedema.^4,5

ARB

• Alternative for patients who are intolerant to ACEI due to cough or angioedema, in whom an ARNI can’t be used.¹
• Patients with HF or EF <40% post-MI, who are intolerant of ACEI (Canada).²

Comments:

• For patients already tolerating an ARB, consider switching to an ARNI to further reduce morbidity and mortality.^1,2 (Canada: switch patients who remain symptomatic or who have a HF hospitalization.²)

Beta-Blocker

• Hemodynamically stable patients with symptoms or prior symptoms, to reduce hospitalizations and mortality.¹
• Also consider for patients with prior or current symptoms and EF 41% to 49% (US).¹

Comments:

• May start beta-blocker at same time as ARNI (or ACEI, or ARB), aldosterone antagonist, and/or SGLT2 inhibitor, but individualize sequencing and titration based on symptoms, functional status, vitals, kidney function, electrolytes, comorbidities, and follow-up.¹ For tips on initiating therapy based on kidney function, see our toolbox, Improving Heart Failure Care.
  • Beta-blocker initiation is best tolerated when the patient is “dry.”¹³
  • Start even if patient is asymptomatic, has improved with other therapies.¹
• Use an evidence-based beta-blocker (carvedilol, bisoprolol, metoprolol succinate [US only]).¹
• Canada: patients with class III or IV heart failure should have their beta-blocker started by a specialist.²

Aldosterone Antagonist (eplerenone or spironolactone)

• Patients with Class II to IV HF symptoms, to reduce hospitalization and mortality, in patients with
  eGFR >30 mL/min/1.73m²and potassium <5 mEq (mmol)/L.¹ (Canada: post-MI with EF ≤40% and HF symptoms or diabetes.²)
• Also consider for patients with prior or current symptoms and EF 41% to 49% (US).¹

Comments:

• May start at same time as ARNI (or ACEI, or ARB), beta-blocker, and/or SGLT2 inhibitor, but individualize sequencing and titration based on symptoms, functional status, vitals, kidney function, electrolytes, comorbidities, and follow-up.¹ For tips on initiating therapy based on kidney function, see our toolbox, Improving Heart Failure Care.
• Stop if potassium cannot be kept <5.5 mEq (mmol)/L.¹

SGLT2 inhibitor

• For patients (with or without diabetes) with HF symptoms, to reduce HF hospitalization and CV mortality.¹
• Also consider for patients with prior or current symptoms and EF 41% to 49% (US).¹

Comments:

• May start at same time as ARNI (or ACEI, or ARB), beta-blocker, and/or aldosterone antagonist, but individualize sequencing and titration based on symptoms, functional status, vitals, kidney function, electrolytes, comorbidities, and follow-up.¹
• Adding empagliflozin (Jardiance) to standard HF treatment in patients with class II to IV HF for ~16 months prevents hospitalization or CV death in ~1 in 14 patients with type 2 diabetes, or ~1 in 26 patients without diabetes. This was driven mostly by hospitalizations.¹¹
• Adding dapagliflozin (Farxiga) to standard HF treatment in patients with class II to IV HF for ~1.5 years may reduce the composite endpoint of worsening HF (hospitalization or urgent visit requiring intravenous HF therapy) or CV death (NNT = 21 [patients with and without diabetes], NNT ~18 [patients with diabetes], or NNT ~22 [patients without diabetes]).¹²

Diuretics

• Patients with fluid retention or a history of fluid retention, to improve symptoms and exercise tolerance.¹

Comments:

• Loops preferred, but thiazides can be considered for patients with hypertension and mild fluid retention.¹
• Diuretic dosage increase may be needed during beta-blocker uptitration.²
• See our chart, Loop Diuretic Use in Heart Failure, for dosing and more.

Education to facilitate HF self-care

• Patients with symptoms or prior symptoms, to improve quality of life, prevent hospitalization, reduce mortality.¹

Avoidance of excessive sodium

• All symptomatic patients, to reduce symptoms and improve diuretic response.^1,14

Comments:

• Limiting sodium to 2 to 3 grams daily, as for general cardiovascular health, is reasonable.^1,14

Exercise (regular physical activity or cardiac rehab)

• Symptomatic but clinically stable patients who are able, to improve function and quality of life.¹

First-Line Alternatives or Add-ons for Select Patients

Hydralazine and Isosorbide Dinitrate

• Patients of African ancestry with Class III or IV HF symptoms (Canada: advanced symptoms) who are symptomatic despite optimized therapy (e.g., as an add-on first-line therapies), to improve symptoms and to reduce morbidity and mortality.^1,2
• Alternative for patients who cannot take an ACEI, ARB, or ARNI (e.g., due to side effects such as hyperkalemia, or kidney insufficiency).^1,2 Consider referring such patients to a heart failure specialist.

Comments:

• Insufficient data on use with ARNI.¹

Ivabradine (Corlanor[US], Lancora [Canada])

• Patients with symptomatic Class II or III stable chronic HF with EF ≤35%, in sinus rhythm with resting heart rate of ≥70 beats per minute (Canada: >70 beats [or ≥77 beats, per product labeling]), in addition to maximally-tolerated guideline-directed therapy (above), including a beta-blocker at a maximally-tolerated dose, or who cannot take a beta-blocker, to reduce HF hospitalization and cardiovascular death (composite endpoint).^1,2,7,8

Comments:

• Reduces HF hospitalization in one in 25 patients vs placebo when added to standard therapy [Evidence level A-1].⁹
• Causes bradycardia in one in 13 patients and atrial fibrillation in one in 100 patients vs placebo.^7,9

Last-Line Add-ons

Digoxin

• Patients with persistent HF symptoms (Canada: moderate to severe symptoms) despite optimized guideline-directed therapy (above), to decrease HF hospitalization.^1,2
• Patients with A Fib who need additional rate control (Canada).²

Comments:

• No loading dose needed for HF.¹
• Consider starting with 0.125 mg every-other-day in patients with renal insufficiency, low lean body mass, or age over 70 years.¹ Doses over 0.25 mg per day rarely needed.¹
• Levels ≥1.2 ng/mL are associated with increased mortality.¹

Vericiguat (Verquvo)(US) (guanylate cyclase stimulator)

• “Niche” drug for patients with symptomatic HF and EF <45% with worsening HF (HF hospitalization within the previous six months or need for outpatient IV diuretics within the previous three months), to reduce the risk of CV death or HF hospitalization.^1,10

Comments:

• Sixty percent of patients in the pivotal clinical trial were on a beta-blocker, aldosterone antagonist, and either an ACEI, ARB, or Entresto.³
• Prevents the composite endpoint (but not individual components) of hospitalization and CV death in ~1 in 33 patients over about one year.^3,10
• Use with a phosphodiesterase-5 inhibitor (e.g., sildenafil) is not recommended (hypotension concern).^3,10