Management of chronic heart failure

The management of chronic heart failure is described as follows:

• general measures
• treatment of mild to moderate heart failure
• treatment of severe heart failure

Six types of treatment have been shown to reduce morbidity and mortality in patients with heart failure:

• angiotensin converting enzyme (ACE) inhibitors
• beta-blockers
• miineralocorticoid receptor antagonists
• sacubitril valsartan
• sodium glucose transporter 2 inhibitors (SGLT2i)
• ivabradine

Treatments aimed at relieving symptomes include:

• diuretics
• digoxin - not only for patients in atrial fibrillation
• hydralazine plus nitrate

NICE state:

Treating heart failure with reduced ejection fraction (3)

• first-line treatments are:
  • ACE inhibitors (consider an ARB licensed for heart failure as an alternative to an ACE inhibitor for patients with heart failure due to left ventricular systolic dysfunction who have intolerable side effects with ACE inhibitors (3))
  • beta-blockers
  • mineralocorticoid receptor antagonists (aldosterone antagonists) e.g. spironolactone
  • SGLT2i
    
    
• specialist initiated treatments
  • sacubitril valsartan
  • ivabradine
  • hydralazine in combination with a nitrate
    
    
• managing all types of heart failure
  • diuretics - should be routinely used for the relief of congestive symptoms and fluid retention in people with heart failure, and titrated (up and down) according to need following the initiation of subsequent heart failure therapies
  • calcium-channel blockers - avoid verapamil, diltiazem and short-acting dihydropyridine agents in people who have heart failure with reduced ejection fraction
  • amiodarone - make the decision to prescribe amiodarone in consultation with a specialist
  • anticoagulants
    • if heart failure and atrial fibrillation, follow the recommendations on anticoagulation in the NICE guideline on atrial fibrillation
    • if heart failure in sinus rhythm, anticoagulation should be considered for those with a history of thromboembolism, left ventricular aneurysm or intracardiac thrombus
  • antiplatelet drugs
    • indiated in HF patients with atherosclerotic arterial disease (including coronary heart disease)

Implantable cardiac defibrillators (ICDs) :

• the Sudden Cardiac Death in Heart Failure (SCD-HeFT) (4) provides evidence for the prophylactic use of ICDs in patients with congestive heart failure (CHF). This trial showed that in patients with CCF, a conservatively programmed, shock only ICF reduced all cause mortality. In comparison with placebo, ICD reduced mortality in New York Heart Association (NYHA) class II but not class III CHF. The SCD-HeFT also included an amiodarone arm, which showed no benefit in the primary prevention of cardiac death

Following the evidence of benefit for ARNIs (angiotensin receptor-neprilysin inhibitor) and sodium glucose transporter 2 inhibitor (SGLT2i) in heart failure with reduced ejection fraction (HFrEF) McMurray et al proposed:

an algorithm for chronic heart failure in HFrEF (heart failure with reduced ejection fraction) in patients whom diuretic therapy has achieved euvolemia (6):

• Step 1: Simultaneous initiation of a beta-blocker and an sodium glucose transporter 2 inhibitor (SGLT2i)
  
  
• Step 2: Addition of sacubitril/valsartan, within 1-2 weeks of Step 1. If SBP <100 mmHG, it may be prudent to first evaluate tolerance with an ARB before switching to ARNI (angiotensin receptor-neprilysin inhibitor)
  
  
• Step 3: Addition of an mineraolocorticoid receptor antagonist (MRA), within 1-2 weeks of Step 2, if renal function is not severely impaired and serum potassium levels are normal. MRAs may also be initiated in Step 2 in patients with troublesome hypotension.

The algorithm can be individualized to specific circumstances and is most appropriate for outpatients.

Caution is required in hospitalized patients with decompensated HF.

This approach achieves treatment with beta-blocker, SGLT2i, ARNI and MRA within 4 weeks. Up-titration to target doses should be pursued after this period.

The algorithm is based on five principles:

1) magnitude of the treatment benefit of each individual drug class is independent of the treatment benefits of other drug classes

2) foundational drugs are effective in reducing morbidity and mortality at low starting doses

3) addition of a new drug class to the treatment yields greater benefit than up-titrating existing drug classes - target doses are often only modestly more effective in comparison with starting doses in reducing risk of CV death

4) safety and tolerability can be improved by proper sequencing of drug classes

5) much of the benefit of foundational treatments can be seen within 30 days

Therapy with all four drug classes should therefore be achieved within 4 weeks.

The conventional approach assumes that clinical trials tested the efficacy and safety of each drug class in presence of all background therapies at target doses - however the majority of patients in heart failure trials were actually receiving sub-evidence based doses of recommended treatment (6,7). Also, if considering trials such as DAPA-HF and EMPEROR-reduced, then substantial proportion of patients were not treated with an MRA or ARNI.

McMurray and Packer expect that this will prevent HF death and HF hospitalizations and will enhance the tolerability of concurrently or subsequently administered treatments.

Notes:

• co-morbidities which may influence the treatment of heart failure (5) the following cardiovascular and non cardiovascular co-morbidities should be detected and treatment should be considered.
  • non cardiovascular
    • anaemia
    • pulmonary disease
    • renal impairment
    • thyroid dysfunction
    • diabetes
  • cardivascular
    • ischemia, coronary heart disease
    • hypertension
    • valvlar dysfunction
    • atrial fibrillation

Reference:

• 1) British Heart Foundation. Factfile 11/99.
• 2) NEJM (1999), 341, 709-17.
• 3) NICE (September 2018).Chronic heart failure in adults: diagnosis and management
• 4) Brady GH et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-3
• 5) European Society of Cardiology (ESC) 2008. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008
• 6) McMurray JJV and Packer M. How Should We Sequence the Treatments for Heart Failure and a Reduced Ejection Fraction? A Redefinition of Evidence-Based Medicine. Circulation. 2020 doi: 10.1161/CIRCULATIONAHA.120.052926
• (7)Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Ryden L, Thygesen K, Uretsky BF. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999; 100: 2312-2318.