Prescribing information



ENTRESTO is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction.1,2

For full safety information, please refer to the GB and NI Summary of Product Characteristics.1,2


Start with ENTRESTO® in your newly diagnosed chronic HFrEF patients

Proven benefits of ENTRESTO in newly diagnosed HFrEF patients3–7

  • Consistent NT-proBNP reductions and reverse cardiac remodelling from baseline4,7
  • Safety and tolerability profile comparable to ACEi (enalapril)3
  • Recommended as first-line treatment by CaReMe UK in patients with LVEF <35%, 2021 ESC Guidelines and the 2022 ACC ECDP Update*8–10
Award sticker: CaReMe UK partnership
Award sticker: Guidelines 2021 as a first-line treatment option
Award sticker: American college of cardiology (ACC) consensus 2021

CaReMe UK recommends sacubitril/valsartan as a first-line treatment option in patients with LVEF <35%.


Across multiple trials, ENTRESTO was extensively studied in newly diagnosed chronic HFrEF patients3–7

pie chart 1: 34% Pioneer-HF n= 303/881
pie chart 2: 29% transition n= 286/991
pie chart 3: 10% prove-HF n= 78/794



Watch our on-demand webinar: Early initiation of ENTRESTO (sacubitril/valsartan): alter the cycle of re-admission in eligible patients with chronic HFrEF

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In newly diagnosed patients, ENTRESTO as first choice helped reduce cardiac stress and improve outcomes vs ACEi3,4

Bar graph showing in newly diagnosed patients, Entresto as first choice reduces cardiac stress and improves outcomes vs ACEi. Entresto (n=134) −73.6%. Enalapril (n=154) −56.2%
Line graph representing Pioneer-HF (n=303): cumulative incidence of CV death or HF rehospitalisation. Entresto (n=141). Enalapril (n=162)

ENTRESTO is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction. ENTRESTO is not indicated for the treatment of acute HF.1,2 Patients in the PIONEER-HF/TRANSITION trial were required to be haemodynamically stabilised from an ADHF episode while in hospital.3,5

Regardless of where patients are in their journey, starting ENTRESTO as early as possible helps improve outcomes vs ACEi (enalapril).3,13,14

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Start with ENTRESTO to improve near and long-term benefits for your patients vs Enalapril3,13,14



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Starting ENTRESTO during hospitalisation may be associated with reduced hospitalisations, reducing hospital budgets and alleviating system burden compared with no initiation or initiation after hospitalisation15


ENTRESTO is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction. ENTRESTO is not indicated for the treatment of acute HF.1,2 Patients in the PIONEER-HF/TRANSITION trial were required to be haemodynamically stabilised from an ADHF episode while in hospital.3,5


How can I alter the cycle of readmission in patients with heart failure?

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PARADIGM-HF (N=8,442): Lower risk of CV death or HF hospitalisation with ENTRESTO vs ACEi16

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ENTRESTO reduced the relative risk of death from cardiovascular causes by 20% vs enalapril (p<0.001). Absolute risk reduction was 3.2%.16

Discover the benefits of ENTRESTO vs ACEi (enalapril) in improving your chronic HFrEF patient’s treatment experience§§11,12

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Summary of the safety profile

The most commonly reported adverse events (AEs) during treatment with ENTRESTO were hypotension (17.6%), hyperkalaemia (11.6%) and renal impairment (10.1%). Angioedema was reported in patients treated with sacubitril/valsartan (0.5%).1,2

Common AE:
Anaemia, hypokalaemia, hypoglycaemia, dizziness, headache, syncope, vertigo, orthostatic hypotension, cough, diarrhoea, nausea, gastritis, renal failure (renal failure, acute renal failure), fatigue, asthenia.1,2

Very common AE:
Hyperkalaemia, hypotension, renal impairment.1,2

Adverse reactions are ranked by System organ class and then by frequency with the most frequent first, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Please click here for safety information


*DISCLAIMER: This is a US guideline and should not be used to guide treatment decisions in the UK.
CaReMe UK: sacubitril/valsartan is recommended as a first-line treatment option for chronic HFrEF where ejection fraction is <35%. Sacubitril/valsartan is to be given in combination with a beta-blocker and MRA. Measure serum sodium, potassium and assess renal function before and after starting, and after each dose increment. If eGFR is 30 to 45 ml/min/1.73 m2, consider lower doses or slower titration of ACEI/ARBs/sacubitril/valsartan or MRAs.8
ESC: ARNI may be used first line as part of cornerstone HFrEF therapy with a BB, MRA and SGLT1 for the treatment of chronic HFrEF patients.
§ACC: ARNIs, ACE-inhibitors or ARBs are recommended as first-line therapy in patients with HFrEF to reduce morbidity and mortality. If patients have chronic symptomatic HFrEF with NYHA class II or III symptoms and they tolerate an ACEi or ARB, they should be switched to an ARNi because of improvement in morbidity and mortality.10
PIONEER-HF was a prospective, multicentre, double-blind, randomised controlled trial designed to assess the safety, tolerability, and efficacy of in-hospital initiation of ENTRESTO compared with enalapril in 881 adult patients in the United States with HFrEF (EF ≤40% and NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL) stabilised during hospitalisation for ADHF. The primary endpoint was time-averaged proportional change in NT-proBNP from baseline through Weeks 4 and 8. An exploratory clinical end point was the outcome of a composite of serious clinical events, which included death, rehospitalisation for heart failure, implantation of a left ventricular assist device, and inclusion on the list of patients eligible for heart transplantation.3
TRANSITION was a randomised, parallel, open-label study comparing pre-discharge vs post-discharge (within 1–14 days) initiation of ENTRESTO in patients with HFrEF (NYHA Class II-IV HF, LVEF ≤40%) following haemodynamic stabilisation after an episode of ADHF.3 A post hoc analysis of the TRANSITION trial comprised hospitalised patients divided into subgroups based on HF history: newly diagnosed HFrEF, or chronic HFrEF diagnosed prior to enrolment in the study. Newly diagnosed was defined as patients who were not known to have HFrEF and/or symptoms or signs of HF prior to hospitalisation and whose index admission was the first presentation of HF. The definition of newly diagnosed HF was irrespective of prior treatment status, including the use of ACEi/ARBs.6
**PROVE-HF is a phase IV, single-arm, multicentre, open-label trial in the US, of which 654 (82.4%) patients completed the 52-week study. This open-label study evaluated the effects of ENTRESTO on biomarkers, cardiac remodelling, and patient-reported outcomes in heart failure with reduced left ventricular ejection fraction. The correlation between the change in concentration of NT-proBNP and E/e′ was added to the statistical analysis plan prior to the database lock.7
††PIONEER-HF Trial Open-label Extension: In PIONEER-HF, 8 weeks after randomisation, patients continued in a 4-week, open-label study with all patients receiving ENTRESTO.8
‡‡Serious clinical outcomes include HF hospitalisation or CV death.
§§Improvement in chronic HFrEF patient treatment experience was determined in the PARADIGM-HF trial by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Patients receiving sacubitril/valsartan had significantly better adjusted change scores in most physical and social activities at 8 months and during 36 months compared with those receiving enalapril. The largest improvement over enalapril was in household chores (adjusted change score difference, 2.35; 95% CI, 1.19-3.50; P < .001) and sexual relationships (adjusted change score difference, 2.72; 95% CI, 0.97-4.46; P = .002); both persisted through 36 months (overall change score difference, 1.69 [95% CI, 0.78-2.60], P < .001; and 2.36 [95% CI, 1.01-3.71], P = .001, respectively).11 At 8 months, sacubitril/valsartan group noted improvements in both KCCQ clinical summary score (+0.64 versus −0.29; P=0.008) and KCCQ overall summary score (+1.13 versus −0.14; P<0.001) in comparison to enalapril group and significantly less proportion of patients with deterioration (≥5 points decrease) of both KCCQ scores (27% versus 31%; P=0.01).12

ACC, American College of Cardiology; ACEi, angiotensin-converting enzyme inhibitor; ADHF, acute decompensated heart failure; AE, adverse event; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor; ARR, absolute risk reduction; BB, beta blocker; BNP, brain natriuretic peptide; CaReMe UK, Cardio-Renal-Metabolic Partnership UK; CI, confidence interval; CV, cardiovascular; ECDP, Expert Consensus Decision Pathway; E/e’, ratio of early mitral inflow velocity to mitral annular early diastolic velocity; EF, ejection fraction; ESC, European Society of Cardiology; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; NT-proBNP, N-terminal-pro-brain natriuretic peptide; NYHA, New York Heart Association; RRR, relative risk reduction; SGLT1, sodium-glucose transporter 1.


  1. ENTRESTO Summary of Product Characteristics. Electronic medicines compendium website, GB. Available at: (Accessed May 2023).
  2. ENTRESTO Summary of Product Characteristics. Electronic medicines compendium website, NI. Available at: (Accessed May 2023).
  3. Velazquez EJ, et al. N Engl J Med 2019;380(6):539–548.
  4. Ambrosy AP, et al. J Am Coll Cardiol 2020;76(9):1034–1048.
  5. Wachter R, et al. Eur J Heart Fail 2019;21(8):998–1007.
  6. Senni M, et al. Eur J Heart Fail 2019;22(2):303–312.
  7. Januzzi JL Jr, et al. JAMA 2019;322(11):1085–1095.
  8. CaReMe HF algorithm. Available at: (Accessed May 2023).
  9. McDonagh TE, et al. Eur Heart J 2021;42(36):3599–3726.
  10. Heidenreich PA, et al. Circulation 2022;145:e895–e1032.
  11. Chandra A, et al. JAMA Cardiol 2018;3(6):498–505.
  12. Lewis EF, et al. Circ Heart Fail 2017;10(8):e003430.
  13. DeVore AD, et al. Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: results of the openlabel extension of the PIONEER-HF trial. Data presented at American College of Cardiology 68th Annual Scientific Session, March 2019.
  14. Morrow DA, et al. Circulation 2019;139(19):2285–2288.
  15. Gaziano TA, et al. JAMA Cardiol 2020;5(11):1236–1244.
  16. McMurray JJ, et al. N Engl J Med 2014;371(11):993-1004.
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UK | May 2023 | 209754-2

Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to Novartis via [email protected] or online through the pharmacovigilance intake (PVI) tool at
If you have a question about the product, please contact Medical Information on 01276 698370 or by email at [email protected]