From the Guidelines
Entresto (sacubitril/valsartan) is not indicated for heart failure with preserved ejection fraction (HFpEF). The most recent and highest quality study, the PARAGON-HF trial 1, did not meet its primary endpoint of reducing heart failure hospitalizations and cardiovascular death in patients with HFpEF (EF ≥45%). Although there was a trend toward benefit that did not reach statistical significance, current guidelines do not recommend Entresto for routine use in HFpEF. Some post-hoc analyses suggested potential benefit in certain subgroups, particularly women and those with ejection fractions in the lower part of the preserved range (45-57%) 1. However, the primary outcome was not met, and other analyses are considered exploratory.
The treatment for HFpEF remains focused on managing symptoms and addressing underlying conditions such as hypertension, using medications like:
- Diuretics
- Beta-blockers
- SGLT2 inhibitors, which have shown benefit in this population. The PARAGON-HF trial results are further supported by another study published in the same year 1, which also found no significant reduction in the primary composite endpoint of cardiovascular death or total HF hospitalizations with sacubitril-valsartan compared to valsartan in patients with HFpEF.
Given the lack of strong evidence supporting the use of Entresto in HFpEF, the current guidelines do not recommend its use for this indication 1. It is essential to prioritize the management of symptoms and underlying conditions in HFpEF patients, rather than relying on Entresto as a treatment option.
From the Research
Entresto Indication for Preserved EF CHF
- Entresto, a combination of an angiotensin receptor neprilysin inhibitor and ARB (valsartan), has been studied as a potential treatment for heart failure with preserved ejection fraction (HFpEF) 2.
- A clinical study published in 2022 found that Entresto significantly improved left ventricular diastolic function in patients with HFpEF and improved quality of life, with a treatment efficacy rate of 94.87% compared to 76.92% in the control group 3.
- Another study published in 2023, a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF, found that sacubitril/valsartan (Entresto) reduced cardiovascular and renal events among patients with HF with mildly reduced or preserved ejection fraction, particularly among those with an LVEF below normal 4.
- While there is evidence to support the use of Entresto in HFpEF, it is essential to note that the treatment of HFpEF is complex and may require a personalized approach, as highlighted in a 2020 review of the evidence 5.
Efficacy and Safety of Entresto in HFpEF
- The 2022 clinical study found that Entresto was safe and effective in treating HFpEF, with significant improvements in echocardiographic indicators, 6-minute walking test, and Minnesota Quality of Life Scale scores 3.
- The 2023 pooled analysis found that sacubitril/valsartan was associated with lower rates of the renal composite endpoint and reduced cardiovascular and renal events among patients with HF with mildly reduced or preserved ejection fraction 4.
- However, a 2018 case report highlighted the potential risk of prolonged first-dose hypotension induced by sacubitril/valsartan, emphasizing the need for careful monitoring and dose adjustment 6.