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ENTRESTO® has proven to be an ESSENTIAL treatment in HFrEF—with over 9+ years of real-world experience1-5

As the first ARNi, ENTRESTO has paved the way in patients with LVEF ≤60%1-4,6-8:
Timeline of clinical trials

*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||

HFrEF LVEF≤40%. HFmrEF LVEF 41%-49%. HFpEF LVEF ≥50%.

~80% of patients with HF have LVEF ≤60% and may be appropriate for ENTRESTO5,7

  • 2024 ACC ECDP FOR HFrEF: ARNi is recommended as the only first-line RASi

  • 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 intolerance10


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).
ACEi/ARBs should only be considered in patients with contraindications, intolerance, or inaccessibility to ARNi.

View ENTRESTO clinical and biomarker data for HFrEF

Learn about the dual mechanism of action of ENTRESTO

Discover support and resources to help your patients start on ENTRESTO

Definitions  
ACC, American College of Cardiology; ACEi, angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ARB, angiotensin II receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; ECDP, Expert Consensus Decision Pathway; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HFSA, Heart Failure Society of America; IV, intravenous; LAE, left atrial enlargement; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy.

References  
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. Maddox TM, Januzzi JL Jr, Allen LA, et al. 2024 ACC Expert Consensus Decision Pathway for treatment of heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2024;83(15):1444-1488. doi:10.1016/j.jacc.2023.12.024
10. 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