What are the initial and subsequent management strategies for patients with advanced heart failure?

From the Guidelines

Management of advanced heart failure requires a comprehensive approach combining pharmacological therapy, device interventions, and potentially advanced therapies, with a focus on optimizing guideline-directed medical therapy (GDMT) and integrating palliative care to address symptoms and quality of life. The initial management strategy should prioritize optimizing GDMT, including ACE inhibitors/ARBs or preferably ARNI (sacubitril/valsartan 24/26 mg twice daily, titrated up to 97/103 mg twice daily as tolerated), beta-blockers (carvedilol 3.125 mg twice daily, titrated to 25 mg twice daily; metoprolol succinate 12.5-25 mg daily, titrated to 200 mg daily; or bisoprolol 1.25 mg daily, titrated to 10 mg daily), and mineralocorticoid receptor antagonists (spironolactone 12.5-25 mg daily or eplerenone 25 mg daily) 1. SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) should be added regardless of diabetes status. Diuretics (furosemide 20-80 mg daily or twice daily, bumetanide 0.5-2 mg daily or twice daily) are used for congestion management.

For eligible patients with reduced ejection fraction (≤35%), device therapy including implantable cardioverter-defibrillators and cardiac resynchronization therapy should be considered. Subsequent management for those who remain symptomatic despite optimal therapy may include advanced options such as inotropic support (milrinone 0.375-0.75 mcg/kg/min or dobutamine 2.5-10 mcg/kg/min), mechanical circulatory support (left ventricular assist devices), or heart transplantation evaluation. Palliative care should be integrated throughout treatment to address symptoms and quality of life, as recommended by the American Heart Association 1.

Key considerations in the management of advanced heart failure include:

• Optimizing GDMT to improve symptoms and reduce hospitalization
• Integrating palliative care to address symptoms and quality of life
• Considering device therapy, including implantable cardioverter-defibrillators and cardiac resynchronization therapy, for eligible patients
• Evaluating advanced options, such as inotropic support, mechanical circulatory support, and heart transplantation, for patients who remain symptomatic despite optimal therapy.

The most recent guidelines from the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines provide a comprehensive framework for the management of advanced heart failure, emphasizing the importance of optimizing GDMT, integrating palliative care, and considering advanced therapies as needed 1.

From the FDA Drug Label

The primary objective of PARADIGM-HF was to determine whether sacubitril and valsartan tablets, a combination of sacubitril and an RAS inhibitor (valsartan), was superior to an RAS inhibitor (enalapril) alone in reducing the risk of the combined endpoint of cardiovascular (CV) death or hospitalization for heart failure (HF) Patients had to have been on an ACE inhibitor or ARB for at least four weeks and on maximally tolerated doses of beta-blockers. The treatment effect reflected a reduction in both cardiovascular death and heart failure hospitalization

The initial management strategy for patients with advanced heart failure may include:

• ACE inhibitors or ARBs: Patients should be on an ACE inhibitor or ARB for at least four weeks
• Beta-blockers: Patients should be on maximally tolerated doses of beta-blockers
• Sacubitril and valsartan tablets: May be considered as an alternative to ACE inhibitors or ARBs, as it has been shown to be superior in reducing the risk of cardiovascular death or hospitalization for heart failure 2 The subsequent management strategy may include:
• Monitoring: Close monitoring of patients for signs and symptoms of heart failure, as well as regular assessment of kidney function and potassium levels
• Dose adjustment: Adjusting the dose of sacubitril and valsartan tablets as needed to achieve optimal therapeutic effect
• Addition of other therapies: Considering the addition of other therapies, such as mineralocorticoid antagonists, diuretics, and implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy-defibrillators (CRT-D), as needed to manage symptoms and slow disease progression 2

From the Research

Initial Management Strategies

• The initial therapy of chronic heart failure is based on diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and in specific cases mineralocorticoid receptor antagonists 3.
• ACE inhibitors have significantly decreased cardiovascular mortality, myocardial infarction (MI), and hospitalizations for heart failure (HF) in patients with asymptomatic or symptomatic left ventricular (LV) systolic dysfunction 4.
• The use of high-dose ACE inhibitors, beta-blockers, and digoxin can provide incremental benefits over low-dose ACE inhibitors alone, with a reduction in mortality and hospitalization 5.

Subsequent Management Strategies

• Angiotensin-receptor-neprilysin inhibitors, such as sacubitril/valsartan, can be used as new therapeutic agents in patients with chronic and progressive heart failure 3.
• Selective angiotensin receptor-1 (AT(1)) antagonists are effective alternatives for those who cannot tolerate ACEIs, and may also be used in combination with ACEIs 6.
• The use of carvedilol, extended-release metoprolol, and bisoprolol should be extended to severe HF patients as these agents have been shown to decrease mortality in this group 6.
• Mechanical circulatory support, such as extracorporeal membrane oxygenation (ECMO), should be recommended for patients who cannot be treated with medicinal therapy 3.

Additional Considerations

• The dosages of ACE inhibitors used in clinical practice are often lower than those proven efficacious in randomized, controlled trials, and optimization of the prescription of proven efficacious therapies has the potential to confer a substantial reduction in the total cost of care for patients with CHF 7.
• Close monitoring of renal function and serum potassium levels is needed when using combination therapy with angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) and ACE inhibitors 4.
• The safety and potential benefits of ARBs in patients with impaired systolic function have been assessed in moderate to large clinical trials, and may be considered for use in patients who remain symptomatic despite standard HF therapy 4.