From the Guidelines
Entresto (sacubitril/valsartan) is not considered a first-line treatment for Heart Failure with preserved Ejection Fraction (HFpEF). The current guidelines and evidence suggest that the first-line treatments for HFpEF typically include diuretics to manage fluid overload and symptoms, along with management of underlying conditions such as hypertension, diabetes, and atrial fibrillation 1. Entresto may be considered in select HFpEF patients, particularly those with ejection fraction in the mildly reduced range (40-50%) or those with elevated natriuretic peptides, based on the results of clinical trials such as the PARAGON-HF trial, which is not directly mentioned in the provided evidence but is relevant to the discussion of sacubitril-valsartan in HFpEF.
The medication works as an angiotensin receptor-neprilysin inhibitor (ARNI), combining valsartan (an angiotensin receptor blocker) with sacubitril (a neprilysin inhibitor) to reduce cardiac wall stress and fibrosis while enhancing beneficial neurohormonal pathways. While Entresto has shown more definitive benefits in heart failure with reduced ejection fraction (HFrEF), as discussed in the guidelines for the management of heart failure 1, its role in HFpEF remains more limited and should be considered as part of a comprehensive treatment approach rather than first-line therapy.
Key points to consider in the management of HFpEF include:
- Management of fluid overload and symptoms with diuretics
- Control of underlying conditions such as hypertension, diabetes, and atrial fibrillation
- Consideration of Entresto in select patients with mildly reduced ejection fraction or elevated natriuretic peptides
- Comprehensive treatment approach tailored to the individual patient's needs and clinical profile, as suggested by the guidelines for heart failure management 1.
From the Research
Entresto for HFpEF
- Entresto (sacubitril/valsartan) has been studied as a potential treatment for Heart Failure with preserved Ejection Fraction (HFpEF) 2, 3, 4.
- A clinical study published in 2022 found that Entresto significantly improved left ventricular diastolic function in patients with HFpEF and improved quality of life 2.
- Another study published in 2017 discussed the potential of Entresto as a treatment option for HFpEF, citing its efficacy in treating Heart Failure with reduced Ejection Fraction (HFrEF) 3.
- However, a 2020 study found that dual-acting RAAS blockade with sacubitril-valsartan failed to improve outcomes in patients with HFpEF compared to stand-alone valsartan 4.
Treatment Guidelines
- Current treatment guidelines for HFpEF recommend management of HF symptoms with sodium and fluid restriction, diuretics for volume overload, and treatment of concomitant comorbidities 5.
- ACEIs, ARBs, calcium channel blockers, and beta-blockers are recommended for HFpEF patients who have other established indications for their use 5.
- RAAS blockers, including MRAs, should be used in the treatment of patients with HFpEF, despite the lack of clear evidence for their efficacy in this specific patient population 4.
Efficacy and Safety
- Entresto has been shown to be safe and effective in treating HFpEF, with significant improvements in left ventricular diastolic function and quality of life 2.
- The incidence of adverse reactions with Entresto was not statistically significant compared to the control group 2.
- However, the effectiveness of Entresto in reducing morbidity and mortality in patients with HFpEF is still uncertain and requires further study 4.