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ENTRESTO® has proven to be an ESSENTIAL treatment in HFrEF—with over 8 years of real-world experience1-5

As the first and only ARNi, ENTRESTO has paved the way in patients with LVEF ≤60%1-4,6-8:
2022 Heart Failure Guideline

*In PARAGON-HF, defined as LVEF ≥45% with structural heart disease (LAE or LVH); median LVEF was 57%. LVEF is a variable measure and the normal range can vary.1
PROVE-HF was a single-arm, open-label study.
PARAGLIDE-HF defined HFmrEF and HFpEF as patients with LVEF >40%. LVEF is a variable measure that can change over time, and the normal range differs according to patient characteristics and method of assessment.
§Worsening HF event was defined as an HF hospitalization, emergency department visit, or out-of-hospital urgent HF visit, all requiring IV diuretics.

2022 AHA/ACC/HFSA HF Guideline strongly recommends ENTRESTO for HFrEF and has expanded its recognition in select HFmrEF and HFpEF patients with LVEF on the lower end of the spectrum5‖
LVEF ≤40%
LVEF 41% to 49%
LVEF ≥50%
~80% of patients with HF have LVEF ≤60% and may be appropriate for ENTRESTO5,7
The 2023 ACC ECDP for HFpEF favors the use of ENTRESTO instead of an ARB for HFpEF patients with LVEF <55% to 60%, unless not feasible due to contraindication, cost, or intolerance.9

In the 2022 HF Guideline, ENTRESTO is recommended as a first-line treatment and to replace well-tolerated ACEi/ARB in patients with NYHA Class II–III HFrEF (Class 1 recommendation). ENTRESTO was also included as a treatment option for HFmrEF (LVEF 41%–49%) and select patients with HFpEF (LVEF ≥50%), particularly for patients with LVEF on the lower end of the spectrum (Class 2b recommendation).

Important Safety Information


  • When pregnancy is detected, discontinue ENTRESTO as soon as possible
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus

ENTRESTO is contraindicated in patients with hypersensitivity to any component...


ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.


ACC, American College of Cardiology; ACEi, angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ARB, angiotensin II receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; BID, twice daily; ECDP, Expert Consensus Decision Pathway; HFmrEF, heart failure with mildly reduced ejection fraction; IV, intravenous; LAE, left atrial enlargement; LVH, left ventricular hypertrophy; NYHA, New York Heart Association.  

1. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.  
2. McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077  
3. Velazquez EJ, Morrow DA, DeVore AD, et al; for the PIONEER-HF Investigators. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380(6):539-548. doi:10.1056/NEJMoa1812851   
4. Januzzi JL Jr, Prescott MF, Butler J, et al; for the PROVE-HF Investigators.  Association of change in N-terminal pro-b-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA. 2019;322(11):1085-1095. doi:10.1001/jama.2019.12821  
5. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. doi:10.1016/j.jacc.2021.12.012  
6. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381(17):1609-1620. doi:10.1056/NEJMoa1908655
7. Vaduganathan M, Claggett BL, Greene SJ, et al. Potential implications of expanded US Food and Drug Administration labeling for sacubitril/valsartan in the US. JAMA Cardiol. 2021;6(12):1415-1423. doi:10.1001/jamacardio.2021.3651
8. Mentz RJ, Ward JH, Hernandez AF, et al. Angiotensin-neprilysin inhibition in patients with mildly reduced or preserved ejection fraction and worsening heart failure. J Am Coll Cardiol. 2023;S0735-1097(23):05429-3. doi:10.1016/j.jacc.2023.04.019
9. Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023;81(18):1835-1878. doi:10.1016/j.jacc.2023.03.393