Is there evidence for the use of Entresto (sacubitril/valsartan) in Heart Failure with preserved Ejection Fraction (HFpEF)?

From the Guidelines

Entresto (sacubitril/valsartan) may be considered for the treatment of heart failure with preserved ejection fraction (HFpEF) based on its potential benefits in reducing heart failure hospitalizations and cardiovascular death, as suggested by the PARAGON-HF trial, although the evidence is not as robust as in heart failure with reduced ejection fraction (HFrEF) 1.

Key Points

• The 2020 international society of hypertension global hypertension practice guidelines suggest that angiotensin receptor-neprilysin inhibitor (ARNI; sacubitril-valsartan) can be considered for the treatment of HFpEF, although the optimal treatment strategy is not known 1.
• The guidelines recommend lifestyle changes, such as diet and exercise, and treating hypertension to reduce the risk of incident HF and HF hospitalization 1.
• The European Society of Cardiology (ESC) guidelines recommend sacubitril/valsartan as a replacement for an ACE-I to further reduce the risk of HF hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE-I, a beta-blocker, and an MRA 1.

Treatment Considerations

• The typical dosing of Entresto starts at 24/26 mg twice daily, titrating to a target dose of 97/103 mg twice daily as tolerated.
• Patients should be monitored for hypotension, hyperkalemia, and renal dysfunction.
• The medication works by simultaneously inhibiting neprilysin (increasing beneficial peptides) and blocking angiotensin II receptors, reducing cardiac stress and improving outcomes in heart failure patients across the ejection fraction spectrum.

Patient Selection

• Patients with HFpEF who may benefit from Entresto are those with ejection fractions in the lower range of preserved (45-57%) and women.
• The FDA has expanded Entresto's indication to include heart failure patients with below-normal ejection fraction, which includes many patients previously classified as HFpEF.

From the Research

Evidence for Entresto in HFpEF

• There are several studies that have investigated the use of Entresto (sacubitril/valsartan) in patients with heart failure with preserved ejection fraction (HFpEF) 2, 3, 4.
• A 2017 study discussed the potential of Entresto as a treatment option for HFpEF, highlighting the limitations of previous treatment modalities and the promise of Entresto in this patient population 2.
• A 2023 review summarized the existing evidence on the use of sacubitril-valsartan in HFpEF, noting that while it did not show a clear benefit in reducing mortality, it may be effective in certain subsets of patients 3.
• A 2024 meta-analysis found that sacubitril/valsartan reduced heart failure hospitalization rates and improved NYHA classification in patients with HFpEF compared to ACEIs and ARBs 4.
• The mechanism of action of sacubitril/valsartan, which combines angiotensin receptor blockade and neprilysin inhibition, may provide benefits in reducing heart failure hospitalization rates and improving symptom severity in HFpEF patients 5, 4.

Key Findings

• Sacubitril/valsartan may reduce heart failure hospitalization rates in HFpEF patients 4.
• Sacubitril/valsartan may improve NYHA classification and reduce NT-proBNP levels in HFpEF patients 4.
• The evidence for the use of sacubitril/valsartan in HFpEF is still evolving, and further studies are needed to fully understand its benefits and limitations 2, 3, 4.