Heart%20failure%20-%20chronic Treatment

Please see the Heart Failure - Acute disease management chart for information on intravenous (IV) drugs administered in the hospital/healthcare facility for emergency cases of HF

Control of Risk and Prevention of Cardiovascular Events

Hypertension and Dyslipidemia

• Recommended optimal BP for HF patients with hypertension is <130/80 mmHg¹; a healthy diet and statin therapy are potential preventive strategies for dyslipidemia
• Please see Hypertension and Dyslipidemia disease management charts for further information

¹Recommendations for BP target goals may vary between countries. Please refer to available guidelines from local health authorities

Diabetes Mellitus (DM)

• Sodium-glucose linked transporter/co-transporter 2 (SGLT2) inhibitors significantly decrease HF events in type 2 diabetes patients with HF, established cardiovascular (CV) disease or high risk for CV disease; Metformin may be used in type 2 diabetes patients with stable HF
• Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)
  • ACE inhibitors and ARBs can prevent the development of end-organ disease, CV complications and risk of HF in patients with diabetes and those without hypertension
• Other agents that may also be given to patients with DM include a beta-blocker, mineralocorticoid receptor antagonist (MRA), an angiotensin receptor-neprilysin inhibitor (ARNI) and Ivabradine
• Please see Diabetes Mellitus disease management chart for further information

Atherosclerotic Disease

• One large-scale trial showed that long-term therapy with an ACE inhibitor decreased the risk of CV death, MI and stroke in patients with known vascular disease
• ACE inhibitors prevent HF in patients who are at high risk of developing HF, have a history of atherosclerotic vascular disease, DM or hypertension with associated CV risk factors
• For prevention of symptomatic HF in pre-HF patients, consider the following: 
  • ACE inhibitor or beta-blocker for LVEF ≤40%  
  • ARB in patients intolerant of ACE inhibitors and with a recent MI and LVEF ≤40%  
  • Beta-blocker (LVEF ≤40%) or statins for patients with a remote or recent history of acute coronary syndrome or MI 
• An ICD may be placed in pre-HF patients who are at least 40 days post-MI with LVEF ≤30% and with >1 year expected survival

Treatment Strategy

• The use of ARNI, ACE inhibitor or ARB, beta-blocker, MRA and SGLT2 inhibitor is important in modifying the course of systolic HF
  
  • Should be considered in all patients with HF because it decreases the risk of HF hospitalization and premature death
  • They are commonly used in conjunction with a diuretic to relieve the symptoms and signs of congestion
  • Initiation of a beta-blocker is better tolerated when the patient is less congested (dry) and an ARNI, ACE inhibitor or ARB when the patient is congested (wet)
• Titration of therapy to maximally tolerated target doses must be done in chronic HFrEF patients in order to achieve maximal benefits of GDMT
• GDMT should be continued, initiated and further optimized in hospitalized patients before discharge  
• May consider continuous IV inotropes and/or vasopressors as a bridge to mechanical circulatory support or heart transplantation in patients with advanced HF with low cardiac output and evidence of organ hypoperfusion, or as palliative therapy to control symptoms and improve functional status
• In COVID-19 infection, inhibition of the renin-angiotensin-aldosterone system is not associated with infection risk or disease severity and should be continued as long as hemodynamically tolerated by the patient
  • CHF patients should continue GDMT regardless of COVID-19 infection

Angiotensin-Converting Enzyme (ACE) Inhibitors

• Recommended for the prevention of HF in patients at risk of this syndrome
• ACE inhibitors should be prescribed to all patients with decreased LVEF of ≤40% regardless of symptoms unless contraindicated or not tolerated
• Started as soon as HF diagnosis is made because of its modest effect on LV remodelling which delays the development of symptomatic CHF in patients with asymptomatic LV dysfunction and those without ventricular dysfunction
• If a patient has recent or current history of fluid retention, diuretics should be started prior to ACE inhibitors to ensure sodium balance, preventing peripheral and pulmonary edema
• An increase in the creatinine and potassium levels is expected after treatment with an ACE inhibitor (or ARB) or ARNI
  • An increase in the creatinine level of up to 3 mg/dL (eGFR >25 mL/min/1.73 m²) or up to 50% above baseline (whichever is smaller) and potassium level to ≤5.5 mmol/L is acceptable 
  • Administration of potassium-lowering agents (eg patiromer and sodium zirconium cyclosilicate) may allow renin-angiotensin-aldosterone system (RAAS) inhibitor initiation or uptitration in a large number of patients with hyperkalemia; consider a specialist referral if with significant renal dysfunction or hyperkalemia

Angiotensin Receptor Blockers (ARBs)/Angiotensin II Antagonists

• Recommended as an alternative in patients who are intolerant of ARNI or ACE inhibitors due to cough or angioedema; patients should also be given a beta-blocker and an MRA
  • Can also be used as alternatives to ACE inhibitors as 1st-line agents in those already on ARB for other indications
• May also be considered in patients with systolic CHF who remain symptomatic despite receiving ACE inhibitor and a beta-blocker and are intolerant of MRA
• Candesartan may be considered for ambulatory patients with symptomatic HFmrEF to decrease the risk of HF hospitalization and CV death 
• Avoid use in patients with recent acute MI and decreased LVEF who are on ACE inhibitor and beta-blocker
• Triple combination of ACE inhibitor, ARB and MRA is not recommended due to increased risk of hyperkalemia

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

• Eg Sacubitril/Valsartan
• Indicated for patients with HFrEF (EF ≤40%), NYHA Class II-III 
• Acts by inhibiting neprilysin which slows down the degradation of natriuretic peptides, bradykinin and other peptides leading to high amounts of circulating A-type natriuretic peptide and BNP resulting in diuresis, natriuresis and relaxation and anti-remodelling of the myocardium
  • Interpret BNP values with caution as BNP levels may rise with ARNI therapy
• Recommended as a replacement for an ACE inhibitor or ARB to further decrease morbidity and mortality in patients with HFrEF NYHA Class II-III
• May consider starting Sacubitril/Valsartan rather than an ACE inhibitor or ARB for patients admitted with new-onset HF or decompensated CHF for reduction of short-term risk of adverse events and for simplification of management (ie the need to initially titrate ACE inhibitor then switch to Sacubitril/Valsartan is avoided)
• Treatment should not be combined with ACE inhibitor or ARB or initiated within 36 hours from the last dose of ACE inhibitor due to a higher risk of angioedema

Beta-Blockers

• Recommended in all stable NYHA Class II-IV patients with HFrEF to relieve angina, unless contraindicated or not tolerated 
• Preferred 1st-line treatment to control ventricular rate for patients in NYHA Class I-III provided they are euvolemic
  • May also be used to control the ventricular rate in HF patients with preserved EF and AF
• Also used in patients with prior MI to reduce mortality, recurrent MI and development of HF
  • Slow down symptom onset and decrease cardiac morbidity in post-MI patients with asymptomatic LV dysfunction
• May be considered for ambulatory patients with symptomatic HFmrEF to decrease the risk of all-cause and CV death
• Prevent ischemia and inhibit the adverse effects of the sympathetic nervous system in HF
• It is recommended to use only evidence-based beta-blockers (eg Bisoprolol, Carvedilol, Metoprolol succinate) in patients with HFrEF and to initiate treatment in a “start low, go slow” approach 

Calcium Channel Blockers

• Dihydropyridine calcium channel blockers are not recommended for HF treatment in patients with HFrEF
  
  • May be used to treat hypertension in patients with high BP despite optimal GDMT
• Non-dihydropyridine calcium channel blockers that are negative inotropes are contraindicated in patients with HFrEF
  
  • However, Diltiazem is sometimes used in patients with CHF and AF to decrease excessive exercise-related heart rates

Digoxin

• May be used to slow a rapid ventricular rate in patients with symptomatic HF, LVEF ≤40% and AF in addition to or prior to a beta-blocker
  
  • Recommended as the preferred second drug, in addition to a beta-blocker, to control the ventricular rate in patients with inadequate response to beta-blocker
• May also be used to decrease HF hospitalizations in NYHA Class II-IV patients with EF ≤40% in sinus rhythm and persisting symptoms despite treatment with optimized GDMT 

Diuretics

• Recommended in NYHA Class II-IV patients with HF and those with clinical manifestations of congestion or fluid overload regardless of EF
  • Start with a low dose and titrate accordingly until clinical improvement is achieved
    • Diuretic dosing may need to be reduced with increasing doses of ARNI, ACE inhibitor or ARB
  • Adjust dose after restoration of dry body weight to avoid risk of dehydration, hypotension and renal dysfunction
• Patients with preserved EF are given diuretics to control volume, manage high BP and relieve ischemia
  • If after management of volume overload patient with preserved EF still has persistent hypertension, ACE inhibitors or ARBs and beta-blockers should be given to achieve SBP <130 mmHg
• May be considered to reduce the risk of HF hospitalization in patients in sinus rhythm with an EF ≤45% who are unable to tolerate a beta-blocker  
• Work synergistically when a different diuretic is used in combination with a loop diuretic for the treatment of resistant edema
• Consider ultrafiltration in patients with refractory volume overload not responding to diuretic therapy

Loop Diuretics

• Preferred diuretic for the treatment of HF
• Used in patients with more severe volume overload or if there is inadequate response to thiazide
  
  • Produce a greater fractional excretion of filtered sodium and more intense, shorter diuresis
• If high doses of a loop diuretic are reached during treatment (ie equivalent of Furosemide 80 mg 12 hourly), may consider switching to a different loop diuretic or adding a thiazide diuretic

Potassium-Sparing Diuretics

• Recommended in patients with excessive potassium losses secondary to the use of loop diuretics
• Also used in combination with thiazides for the treatment of hypertension
• Caution is needed if a potassium-sparing diuretic is used in addition to ACE inhibitor or ARB and MRA

Thiazide Diuretics

• May be effective as a monotherapy in HF patients with mild congestion and normal renal function

Combinations

• Thiazides or Metolazone can be used in combination with loop diuretics for a synergistic effect in patients with persistent fluid retention despite high-dose loop diuretic treatment
• Chronic daily use of these agents, especially of Metolazone, should be avoided because of the risk of electrolyte imbalance and dehydration

Hydralazine and Isosorbide Dinitrate

• Given to NYHA Class III-IV black patients with HFrEF who remain symptomatic despite optimal standard therapy with ARNI, ACE inhibitor or ARB, beta-blocker, aldosterone antagonist and SGLT2 inhibitor
• Considered an alternative in patients who cannot tolerate ACE inhibitors, ARBs, or ARNI or in whom these agents are contraindicated and if no other treatment options are available
• Hydralazine and Isosorbide have complementary dilating actions
  
  • Hydralazine may interfere with the molecular mechanisms responsible for the progression of HF
  • Isosorbide may also inhibit abnormal myocardial and vascular growth and therefore may reduce ventricular remodeling

Ivabradine

• A highly selective sinus node I(f) channel inhibitor that is known for slowing the heart rate
• Approved for use in patients with a heart rate of ≥75 bpm
• May be considered to reduce mortality and the risk of HF hospitalization in patients in sinus rhythm with an LVEF ≤35%, heart rate of ≥70 bpm at rest, with persisting symptoms (NYHA Class II-III) and with:
  • Inadequate response to GDMT including evidence-based dose of beta-blocker 
  • Intolerance or contraindication to beta-blockers or when there is treatment failure after beta-blocker therapy; patient should also be given an ACE inhibitor (or ARB/ARNI) and MRA

Mineralocorticoid Receptor Antagonists (MRA)/Aldosterone Antagonists

• Recommended for NYHA Class II-IV patients with HFrEF to reduce morbidity and mortality
  
  • Treatment option for patients with HFpEF (EF ≥45%, increased BNP, eGFR >30 mL/min/1.73 m², creatinine <2.5 mg/dL, potassium <5 mEq/L) to reduce hospitalizations
• Recommended also for NYHA Class II symptomatic patients with a history of previous CV hospitalization or an elevated level of natriuretic peptide 
• Spironolactone and Eplerenone block receptors that bind aldosterone and other corticosteroids and are best characterized as MRAs 
• Spironolactone is recommended for patients who remain severely symptomatic despite appropriate doses with ACE inhibitors, loop diuretics and Digoxin
  • May be considered for ambulatory patients with symptomatic HFmrEF without contraindications to decrease the risk of HF hospitalization and CV death
• Eplerenone is considered in patients with systolic HF who still have mild symptoms despite receiving standard therapy of ACE inhibitors and beta-blockers; has no antiandrogenic effects
• Renal dysfunction and hyperkalemia may lead to underutilization of MRA
  
  • Administration of potassium-lowering agents may allow MRA initiation or uptitration in a large number of patients with hyperkalemia 
  • Serial monitoring of serum electrolytes and renal enzymes is advised

Nitrates 

• A short-acting oral or transcutaneous nitrate is an effective treatment for angina and is safe in patients with HF

Rivaroxaban

• May be considered, in addition to Aspirin therapy, for ambulatory patients with CAD and CHF in NYHA Class I/II with an LVEF >30% to decrease the risk of stroke and CV death

Sodium-Glucose Linked Transporter/Co-transporter 2 (SGLT2) Inhibitors

• Dapagliflozin and Empagliflozin are indicated for patients with HFrEF (EF ≤40%) with or without diabetes, NYHA Class II-IV, to decrease the risk of HF hospitalization and death
• A clinical trial showed the benefit of Empagliflozin in the treatment of symptomatic HF patients with LVEF >40% and elevated levels of natriuretic peptides     
• Sotagliflozin initiated before or shortly after discharge reduced CV deaths and HF hospitalizations in a clinical trial
• Prior to initiation of therapy, ensure an eGFR of ≥30 mL/min/1.73 m² for Dapagliflozin and ≥20 mL/min/1.73 m² for Empagliflozin*

*Reference: 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction. http://www.acc.org.

Tolvaptan

• A vasopressin V₂ receptor antagonist that may be used in the short term for the treatment of resistant hypervolemic hyponatremia despite water restriction and GDMT
  • May be given during hospitalization to patients with HFrEF who have fluid retention unresponsive to treatment with other diuretics including loop diuretics 
• Tolvaptan given during hospitalization for AHF may be used by patients with HFpEF after discharge to control congestion
• Adverse effects may include thirst and dehydration

Vericiguat

• An oral soluble guanylate cyclase stimulator that may be considered to decrease the risk of HF hospitalization and CV death following a HF hospitalization or outpatient IV diuretic therapy in select high-risk patients with HFrEF NYHA Class II-IV and LVEF <45% with worsening HF despite GDMT

Adjunctive Therapy

Coenzyme Q10 (CoQ10) 

• A lipid-soluble cofactor found in the mitochondrial inner membrane that has antioxidant properties and a bioenergetic role; it is predominantly located in the myocardium
• Q-SYMBIO trial, a double-blind trial on CoQ10 as adjunctive therapy of CHF, found that supplementation with CoQ10 was safe and resulted in HF symptom improvement and reduction in major adverse CV events and mortality
• As trials on CoQ10 have shown mixed results, further evidence is needed to establish beneficial effect

Treatment of Comorbidity

Anticoagulation

• Long-term anticoagulation should be given to patients with CHF with permanent-persistent-paroxysmal AF and a CHA₂DS₂-VASc score of ≥2 in men and ≥3 in women 
  • In eligible patients, direct oral anticoagulant (DOAC) is recommended over Warfarin 
  • Reasonable therapy for patients with CHF with permanent-persistent-paroxysmal AF in the absence of additional risk factors 

Intravenous Iron Replacement

• Consider giving in symptomatic patients with HFrEF (NYHA Class II and III) and iron deficiency (serum ferritin <100 ng/mL or 100-300 ng/mL if transferrin saturation is <20%) with or without anemia for alleviation of HF symptoms and improvement of exercise capacity and quality of life
  • Also considered in HF patients who are symptomatic and hospitalized recently for HF with LVEF <50% and iron deficiency to decrease the risk of HF hospitalization

Cardiac Rehabilitation

• Useful in patients who are clinically stable and able to participate in exercise programs
• Includes monitored exercise, psychological support & education about lifestyle changes to reduce CV risks
• Several meta-analyses demonstrated cardiac rehabilitation improves functional capacity, exercise duration and health-related quality of life and decreases risk of hospitalizations and mortality in HF patients
  • An exercise-based cardiac rehabilitation is recommended in symptomatic patients with HFrEF who are stable to decrease risk of hospitalization
  • Consider a supervised program in patients with frailty, more severe disease or comorbidities
• Helpful in monitoring symptoms and supporting drug titration 
• Helps reduce patient anxiety and uncertainty
• Following revascularization, patients may also be referred for cardiac rehabilitation

Sleep and Breathing Disorders

• Patients with symptomatic HF usually have sleep-related breathing disorders (eg central or obstructive sleep apnea)
• Weight loss in obese patients, smoking cessation and abstinence from alcohol are recommended to decrease the risks
• Continuous positive airway pressure (CPAP) should be considered in polysomnograph-documented obstructive sleep apnea to improve daily functional capacity and quality of life

Depression and Mood Disorder

• Screening for endogenous or prolonged reactive depression in patients with HF should be done following diagnosis and at periodic intervals as clinically indicated
• Initiate appropriate pharmacotherapy (eg selective serotonin receptor uptake inhibitors) and provide psychosocial support