What are the guideline-based recommendations for Heart Failure (HF) medications?

From the Guidelines

Guidelines for heart failure medications recommend a stepwise approach starting with foundational therapies, including ACE inhibitors or ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as stated in the most recent study 1.

Foundational Therapies

The first-line treatments include:

• ACE inhibitors (like lisinopril 10-40 mg daily or enalapril 2.5-20 mg twice daily) or ARBs (such as losartan 25-100 mg daily) to reduce afterload and remodeling, along with
• beta-blockers (metoprolol succinate 12.5-200 mg daily, carvedilol 3.125-25 mg twice daily, or bisoprolol 1.25-10 mg daily) to decrease heart rate and workload. For patients with reduced ejection fraction (HFrEF),
• mineralocorticoid receptor antagonists (spironolactone 12.5-50 mg daily or eplerenone 25-50 mg daily) should be added to reduce fibrosis and improve survival, as supported by 1.

Additional Therapies

Newer agents like

• SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) are now recommended regardless of diabetes status due to their mortality benefits, as highlighted in 1.
• Diuretics (furosemide 20-80 mg daily or as needed) are used for symptom management but don't improve survival. For patients who remain symptomatic, additional options include:
• hydralazine/isosorbide dinitrate (especially beneficial in Black patients),
• ivabradine (for those with elevated heart rates despite beta-blockers),
• or sacubitril/valsartan (an ARNI that replaces ACE inhibitors/ARBs in eligible patients), as discussed in 1.

Implementation and Monitoring

Medication initiation should start at low doses with gradual titration while monitoring blood pressure, heart rate, renal function, and electrolytes. The goal is to reach target doses that have demonstrated mortality benefits in clinical trials while maintaining patient tolerability, as emphasized in 1. Contemporary guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) includes multiple medications proven to substantially extend survival, reduce hospitalization, and improve patient-reported quality of life, as stated in 1.

From the FDA Drug Label

14 CLINICAL STUDIES

Dosing in clinical trials was based on the total amount of both components of sacubitril and valsartan, i.e., 24/26 mg, 49/51 mg, and 97/103 mg were referred to as 50 mg, 100 mg, and 200 mg, respectively. 14. 1 Adult Heart Failure PARADIGM-HF PARADIGM-HF was a multinational, randomized, double-blind trial comparing sacubitril and valsartan and enalapril in 8,442 adult patients with symptomatic chronic heart failure (NYHA class II–IV) and systolic dysfunction (left ventricular ejection fraction ≤ 40%) Patients had to have been on an ACE inhibitor or ARB for at least four weeks and on maximally tolerated doses of beta-blockers. Patients with a systolic blood pressure of less than 100 mmHg at screening were excluded The primary objective of PARADIGM-HF was to determine whether sacubitril and valsartan, 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)

The guideline-based recommendations for Heart Failure (HF) medications include:

• Sacubitril and valsartan as a combination of sacubitril and an RAS inhibitor (valsartan)
• Enalapril as an RAS inhibitor
• Beta-blockers at maximally tolerated doses
• Mineralocorticoid antagonists and diuretics as commonly used medications in HF patients 2

From the Research

Guideline-Based Recommendations for Heart Failure (HF) Medications

The following are guideline-based recommendations for HF medications:

• The use of quadruple therapy, including Angiotensin receptor blocker/neprilysin inhibitors, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors, is recommended for reduction in hospitalizations, all-cause mortality, and cardiovascular mortality in patients with Heart Failure with Reduced Ejection Fraction (HFrEF) 3.
• Sacubitril/valsartan should be preferred as first-line therapy for HFrEF, instead of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker 4.
• The four foundation HFrEF drugs are the angiotensin receptor/neprilysin inhibitor, beta-adrenergic blocking agents, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors, regardless of the presence of type-2 diabetes mellitus 4.
• These four HFrEF drug classes should be introduced over a short-term period of four to six weeks, guided by a safety protocol, followed by a dose up-titration period of 8 weeks 4.
• Ivabradine and sacubitril/valsartan increase pharmacotherapy options for the treatment of HFrEF, but are not yet first-line agents 5.
• Diuretics are recommended for symptom relief in patients with HFrEF 3.
• Other medications such as intravenous iron, ivabradine, hydralazine/nitrates, and vericiguat may also have a role in certain subgroups of HFrEF patients 3, 6.

Medication Classes and Their Effects

The following medication classes and their effects are recommended:

• Beta blockers: reduce blood pressure and heart rate 6.
• Renin-angiotensin-aldosterone system inhibitors: reduce blood pressure, and impair renal function and increase potassium levels 6.
• Sacubitril/valsartan: reduce mortality and can be used in place of an ACE inhibitor or an ARB 7.
• Sodium-glucose co-transporter 2 inhibitors: reduce mortality and can be used in addition to current therapies 7.
• Ivabradine: reduce heart rate and can be used to reduce the combined endpoint of cardiovascular mortality or heart failure hospital admission 5.