What is the role of sacubitril-valsartan in treating chronic heart failure?

From the Guidelines

Sacubitril-valsartan is a first-line medication for treating chronic heart failure with reduced ejection fraction (HFrEF), offering significant benefits in reducing mortality and hospitalizations. The standard starting dose is 49/51 mg twice daily, which can be titrated to a target dose of 97/103 mg twice daily as tolerated 1. For patients with severe renal impairment or those not currently on ACE inhibitors/ARBs, a lower starting dose of 24/26 mg twice daily is recommended 1. Before initiating therapy, any ACE inhibitor should be discontinued at least 36 hours prior to prevent angioedema risk. Common side effects include hypotension, hyperkalemia, cough, and dizziness. Renal function and potassium levels should be monitored regularly. This medication works through a dual mechanism: sacubitril inhibits neprilysin, increasing beneficial peptides that promote vasodilation and natriuresis, while valsartan blocks angiotensin II receptors, reducing vasoconstriction and sodium retention.

Some key points to consider when using sacubitril-valsartan include:

• The medication should be initiated de novo in patients hospitalized with acute HFrEF before discharge in the absence of contraindications 1.
• ARNi may be initiated de novo in patients with chronic symptomatic HFrEF to simplify management, although data are limited 1.
• The PIONEER-HF trial showed that ARNi reduced NT-proBNP levels in patients hospitalized for acute decompensated HF without increased rates of adverse events 1.
• Sacubitril-valsartan has been approved for patients with symptomatic HF, and its effects and potential off-target effects may be complex with inhibition of the neprilysin enzyme, which has multiple biological targets 1.

Overall, sacubitril-valsartan is a valuable treatment option for patients with HFrEF, offering significant benefits in reducing mortality and hospitalizations, and its use should be considered in accordance with current guidelines and clinical evidence 1.

From the FDA Drug Label

Sacubitril and valsartan tablet is a combination of sacubitril, a neprilisin inhibitor, and valsartan, an angiotensin II receptor blocker, and is indicated: • to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. • for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.

The role of sacubitril-valsartan in treating chronic heart failure is to reduce the risk of cardiovascular death and hospitalization in adult patients, with benefits most evident in those with left ventricular ejection fraction (LVEF) below normal 2.

• Key benefits: reduction of cardiovascular death and hospitalization risk
• Target population: adult patients with chronic heart failure, especially those with LVEF below normal
• Additional use: treatment of symptomatic heart failure in pediatric patients aged one year and older with systemic left ventricular systolic dysfunction 2.

From the Research

Role of Sacubitril-valsartan in Treating Chronic Heart Failure

• Sacubitril-valsartan is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) that has been shown to be effective in treating chronic heart failure with reduced ejection fraction (HFrEF) 3, 4, 5.
• The medication has been found to reduce the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure, as well as reduce death from any cause and limit the progression of heart failure 4.
• Sacubitril-valsartan has been compared to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and has been found to have a beneficial effect in patients with HFrEF, with a similar safety and tolerability profile 3, 6, 5.
• The medication may also be effective in treating patients with mid-range or preserved ejection fraction, although additional clinical trial data are needed to confirm this 6, 7.

Clinical Outcomes and Benefits

• Studies have shown that sacubitril-valsartan is associated with improved clinical outcomes, including reduced morbidity and mortality, compared to ACE inhibitors or ARBs 5.
• The medication has been found to be effective in reducing heart failure-related emergency care visits, all-cause hospitalization, and all-cause mortality 5.
• Sacubitril-valsartan may also have anti-aging properties and be effective in treating hypertension, particularly in elderly patients with age-related hypertension phenotypes 7.

Potential Uses and Future Directions

• Sacubitril-valsartan may be used as a first-line therapy in outpatient or in-hospital HFrEF patients, and possibly also in HFmrEF patients 6.
• The medication may be effective in suppressing the age-related continuum from hypertension to heart failure, and could be clinically useful not only for secondary prevention, but also as primary prevention of heart failure in uncontrolled elderly hypertensive patients 7.
• Further research is needed to confirm the potential benefits of sacubitril-valsartan in different patient populations and to explore its use in combination with other medications, such as sodium-glucose co-transporter 2 inhibitors 6.