From the Guidelines
ARNI medications, or Angiotensin Receptor-Neprilysin Inhibitors, are recommended for patients with heart failure with reduced ejection fraction (HFrEF) as they have been shown to reduce morbidity and mortality. The most common ARNI is sacubitril/valsartan (Entresto), typically started at 24/26 mg twice daily and titrated up to a target dose of 97/103 mg twice daily as tolerated 1. Treatment should be continued indefinitely as part of a comprehensive heart failure management plan. Before starting, discontinue ACE inhibitors at least 36 hours prior to avoid angioedema risk, and check baseline blood pressure, kidney function, and potassium levels. ARNIs work by combining angiotensin receptor blockade (reducing harmful vasoconstriction) with neprilysin inhibition (preventing breakdown of beneficial peptides like natriuretic peptides). This dual mechanism enhances beneficial neurohormonal pathways while blocking harmful ones, leading to improved cardiac function, reduced hospitalizations, and decreased mortality in heart failure patients, as supported by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
Key Considerations
- ARNI should be initiated de novo in patients hospitalized with acute HFrEF before discharge in the absence of contraindications, as suggested by the PARADIGM-HF trial and the PIONEER-HF trial 1.
- The use of ARNI is associated with the risk of hypotension and renal insufficiency and may lead to angioedema, as well.
- Common side effects include hypotension, hyperkalemia, dizziness, and rarely angioedema, requiring regular monitoring during treatment.
- The 2024 DCRM 2.0 multispecialty practice recommendations also support the use of ARNI over ACEi or ARB for HFrEF patients, citing its benefits in improving symptoms and physical limitations 1.
Monitoring and Management
- Monitor disease progression with CKD and HF biomarkers, including natriuretic peptide (NTproBNP or BNP) and albuminuria (UACR) 1.
- Regularly assess blood pressure, kidney function, and potassium levels to minimize the risk of adverse effects.
- Adjust the treatment plan as needed to optimize patient outcomes and minimize potential side effects.
From the Research
Arni Med Overview
- Arni med, also known as sacubitril/valsartan, is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT1) receptor 2.
- It has been shown to be superior to angiotensin-converting enzyme (ACE) inhibitors for improving the prognosis in patients with heart failure 2, 3.
- Sacubitril/valsartan has been developed for the management of hypertension, due to its unique anti-aging properties, although the clinical evidence of mechanism has not been well validated 2.
Clinical Uses
- Sacubitril/valsartan is used in the treatment of heart failure with reduced ejection fraction (HFrEF) and has been shown to improve quality of life and longevity in patients with HFrEF 3, 4.
- It has also been used in the management of hypertension, particularly in elderly patients with age-related hypertension phenotypes, such as drug-uncontrolled (resistant) hypertension and nocturnal hypertension 2.
- Additionally, sacubitril/valsartan has been shown to improve hemodynamic parameters in patients with advanced heart failure awaiting heart transplantation 5.
Efficacy and Safety
- Sacubitril/valsartan has been shown to be effective in reducing the risk of cardiovascular death or heart failure hospitalization in patients with HFrEF, with similar efficacy in both men and women 4.
- It has also been shown to be safe and well-tolerated, with a similar safety profile to ACE inhibitors 3, 6.
- The combination of sacubitril and valsartan has been shown to be more effective than previous neprilysin inhibitors in reducing morbidity and mortality in heart failure, while preserving a safety profile comparable to standard ACE inhibitor therapy 6.