From the Guidelines
Entresto is not indicated for heart failure with preserved ejection fraction (HFpEF) based on the most recent and highest quality evidence available. The management of HFpEF has largely been focused on symptom improvement, reducing congestion with diuretics, and treating cardiovascular and non-cardiovascular comorbidities 1. Recent breakthroughs have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce composite cardiovascular death or HF hospitalizations in patients with HFpEF 1. However, there is no mention of Entresto (sacubitril/valsartan) being indicated for HFpEF in the latest systematic review of clinical practice guidelines and recommendations 1. Some key points to consider in the management of HFpEF include:
- Symptom improvement and reducing congestion with diuretics
- Treating cardiovascular and non-cardiovascular comorbidities
- The use of SGLT2 inhibitors to reduce composite cardiovascular death or HF hospitalizations 1 It is essential to note that the current evidence does not support the use of Entresto for HFpEF, and treatment decisions should be based on the most recent and highest quality evidence available 1.
From the Research
Entresto Indication in HFpEF
- Entresto, also known as sacubitril/valsartan, is a drug that has been approved for the treatment of heart failure with reduced ejection fraction (HFrEF) 2, 3, 4.
- However, its indication in heart failure with preserved ejection fraction (HFpEF) is still being studied and debated.
- A study published in 2021 discussed the potential benefits of sacubitril/valsartan in HFpEF, but noted that more research was needed to fully understand its effects in this patient population 2.
- The PARAGON-HF trial, which was published in 2025, evaluated the efficacy and safety of sacubitril/valsartan in patients with HFpEF across different age groups, and found that the treatment benefits of sacubitril/valsartan were retained in older patients, although they were more likely to experience hypotension 5.
- Another study published in 2020 found that sacubitril/valsartan reduced systolic blood pressure in patients with HFpEF, and that the optimal achieved systolic blood pressure was between 120-129 mmHg 6.
- Overall, while Entresto is not currently indicated for HFpEF, the available evidence suggests that it may have potential benefits in this patient population, and further research is needed to fully understand its effects 2, 5, 6.
Key Findings
- The PARAGON-HF trial found that sacubitril/valsartan reduced the primary composite outcome of total HF hospitalizations and cardiovascular death in patients with HFpEF, although the effect was not modified by age 5.
- The study published in 2020 found that sacubitril/valsartan reduced systolic blood pressure in patients with HFpEF, and that this reduction was associated with improved outcomes 6.
- The available evidence suggests that sacubitril/valsartan may have potential benefits in patients with HFpEF, although more research is needed to fully understand its effects 2, 5, 6.
Study Limitations
- The available evidence is based on a limited number of studies, and more research is needed to fully understand the effects of sacubitril/valsartan in patients with HFpEF 2, 5, 6.
- The PARAGON-HF trial had a limited sample size, and the results may not be generalizable to all patients with HFpEF 5.
- The study published in 2020 had a limited follow-up period, and the long-term effects of sacubitril/valsartan in patients with HFpEF are not well understood 6.