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
Even when patients do not exhibit apparent symptoms, cardiac damage is constantly occurring3
Modest changes in LVEF may be clinically important; the adjusted risk of CV-related mortality increases 2 to 8-fold beyond a >10-unit decline in LVEF (P<0.001).4
deterioration for cardiac myocytes in failing human hearts compared with healthy hearts5
each year where HF is the primary diagnosis. Around half of those diagnosed with HF in the UK die within 5 years of their diagnosis6
greater risk of death in the first month after just one HF hospitalisation in comparison with non-hospitalised patients7,8
of HFrEF patients may experience sudden cardiac death, even when their symptoms have not worsened9
A multi-pathway, disease-modifying approach can optimally target cardiac damage, reversing it and subsequently improving disease trajectory10
The current expert-recommended ESC guideline recommends Entresto as a replacement for ACEi in eligible HFrEF patients to reduce the risk of HF hospitalisations and death11
*CaReMe UK recommendation for chronic HFrEF patients where ejection fraction <35%.12
See how CaReMe UK* supports ENTRESTO as a first-line treatment option in an integrated disease-modifying approach in chronic HFrEF12
Despite recommendations, the use of ENTRESTO is significantly lower than expected by NICE14
ENTRESTO significantly improved mortality and morbidity outcomes, showing greater risk reduction in CV death and HF hospitalisations (HR 0.80, P<0.001).¶15
However, the annual volume of ENTRESTO used in primary and secondary care prescribing between January 2019 and December 2020 was much lower than expected.14
Observed and expected use of sacubitril/valsartan in England14
Sacubitril/valsartan – observed use and range of expected use in primary and secondary care prescribing from January 2019 to December 2020§
The annual volume of medicine used was between 70% and 75% lower than expected14
ENTRESTO has a dual MoA that simultaneously inhibits vasoconstriction and promotes vasodilation1,2
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
*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.12
†ESC: ARNI may be used first line as part of cornerstone HFrEF therapy with a BB, MRA and SGLT2i 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.13
§For the 12-month period from January 2020 to December 2020, the graph shows the expected and observed use and the ratio between them. Defined daily doses were not available for this formulation, so tablets were used to measure uptake.
¶The PARADIGM-HF trial randomised 8,442 symptomatic HFrEF patients to receive ENTRESTO or enalapril. The primary endpoint was a composite of CV death or first HF hospitalisation.15
ACC, American College of Cardiology; ACEi, angiotensin-converting enzyme inhibitor; ADD, actual daily dose; AE, adverse event; ARNI, angiotensin receptor neprilysin inhibitor; BB, beta blocker; CaReMe UK, Cardio-Renal-Metabolic Partnership UK; CV, cardiovascular; ESC, European Society of Cardiology; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio; LVEF, left ventricular ejection fraction; MoA, mode of action; MRA, mineralocorticoid receptor antagonist; NICE, The National Institute for Health and Care Excellence; NYHA, New York Heart Association; QoL, quality of life; RAAS, renin-angiotensin-aldosterone system; SGLT2i, sodium glucose co-transporter-2 inhibitor.
References:
- ENTRESTO Summary of Product Characteristics. Electronic medicines compendium website, GB. Available at: https://www.medicines.org.uk/emc/product/7751/smpc. (Accessed May 2023).
- ENTRESTO Summary of Product Characteristics. Electronic medicines compendium website, NI. Available at: https://www.emcmedicines.com/en-gb/northernireland/medicine?id=a1393009-... (Accessed May 2023).
- Mann DL, Bristow MR. Circulation 2005;111(21):2837–2849.
- Strange G, et al. Eur J Heart Fail 2021;23(4):555–563.
- Konstantinidis K, Whelan RS, Kitsis RN. Thromb Vasc Biol 2012;32(7):1552–1162.
- British Heart Foundation. Heart failure: a blueprint for change. Available at: https://www.bhf.org.uk/-/media/files/health-intelligence/heart-failure-a.... (Accessed May 2023).
- Solomon SD, et al. Circulation 2007;116(13):1482–1487.
- Okumura N, et al. Circulation 2016;133(23):2254–2262.
- Packer M. Eur Heart J. 2020;41(18):1757–1763.
- Vaduganathan M, et al. Lancet 2020;396(10244):121–128.
- McDonagh TE, et al. Eur Heart J 2021;42(36):3599–3726.
- CaReMe UK HF algorithm. Available at: https://www.britishcardiovascularsociety.org/__data/assets/powerpoint_do.... (Accessed May 2023).
- Heidenreich PA, et al. Circulation 2022;145:e895–e1032.
- NHS digital. NICE Technology Appraisals in the NHS in England (Innovation Scorecard) To December 2020. Available at: https://digital.nhs.uk/data-and-information/publications/statistical/nic.... (Accessed May 2023).
- McMurray JJ, et al. N Engl J Med 2014;371(11):993–1004.