ENTRESTO is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction.1,2
Consider ENTRESTO® as your first choice in place of an ACEi/ARB, wherever your patients are in their chronic HFrEF journey1–15
Patients on ENTRESTO experienced improved QoL, reduced hospitalisations and decreased mortality vs ACEi (enalapril)*1–9
Could your newly diagnosed or hospitalised chronic HFrEF patients benefit from ENTRESTO?‡ Learn more by selecting an option below
There is a wealth of data supporting the use of ENTRESTO in your chronic HFrEF patients3–11
ENTRESTO showed superior efficacy in reducing HF hospitalisations, CV death, and improving QoL, with a generally comparable safety and tolerablity profile vs ACEi (enalapril). More patients experienced hypotension, elevated serum creatinine (≥2.5 mg/dl) and elevated serum potassium (>6.0 mmol/l) with ENTRESTO compared to ACEi (enalapril)§1,2,5–7
ENTRESTO showed improvements in reverse cardiac remodelling, with comparable safety vs ACEi (enalapril); (the primary endpoint was not met in the EVALUATE-HF trial)¶‖9
ENTRESTO was associated with reverse cardiac remodelling and improvements in markers of cardiac function. Safety events were comparable to those reported in previous trials**11
ENTRESTO showed significantly greater reductions in NT-proBNP and exploratory clinical outcomes, with comparable safety vs ACEi (enalapril), when initiated in hospital following haemodynamic stabilisation after an ADHF††,‡‡8
ENTRESTO showed comparable safety and tolerability when initiated pre- or post-discharge following haemodynamic stabilisation after an ADHF§§10
Download the ENTRESTO clinical trial summaries for more information
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
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).
*DISCLAIMER: Patients in the PIONEER-HF/TRANSITION trials were required to be haemodynamically stablised from an ADHF while in hospital. In a post-hoc analysis of this study, the differences in outcomes of the KCCQ between treatment arms were assessed. Patients in the ENTRESTO group had significantly better adjusted change scores in 7/10 physical and social activities vs enalapril. The largest improvements over enalapril were in household chores (adjusted change score difference, 2.35 [95% CI, 1.19–3.50], P<0.001) and sexual relationships (adjusted change score difference, 2.72 [95% CI: 0.97–4.46], P=0.002); both persisted through 36 months (overall change score difference, 1.69 [95% CI: 0.78–2.60], P<0.001; and 2.36 [95% CI: 1.01–3.71], P=0.001, respectively).7
†Schematic representation of the effect of ENTRESTO on the progression of the disease, based on PARADIGM HF3–6 and PIONEER HF7 trials. PARADIGM HF was a multinational, randomised, double-blind trial comparing ENTRESTO to enalapril in 8442 symptomatic (NYHA Class II IV) HFrEF patients (LVEF ≤40%, amended later to ≤35%). For the primary endpoint, composite of CV death or first HF hospitalisation, ENTRESTO was superior to enalapril (P<0.0001). The median follow-up duration was 27 months.5 A post hoc analysis of PARADIGM HF estimated the long-term treatment effects of ENTRESTO vs enalapril by deriving actuarial estimates of age-specific event rates and expected survival times using data regarding the age at randomisation and the age at the time of an outcome event. Survival analysis was performed using the patients’ age as the time scale (rather than the time since randomisation) to estimate the projected effect of ENTRESTO vs enalapril over the duration of patients’ lifetimes. The effect of treatment on the average duration of event-free survival was estimated by comparing the area under the survival curves.3 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 endpoint 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.8
‡ENTRESTO is indicated in adult patients for 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 while in hospital.8,10
§PARADIGM-HF: ENTRESTO showed superiority over enalapril for reducing death from cardiovascular causes or first hospitalisation for worsening heart failure (HR, 0.80 [95% CI: 0.73-0.87], P<0.001).5
¶EVALUATE-HF: The primary endpoint of the between-group difference in change in aortic impedance (Zc) from baseline to Week 12 was not met.9
‖The primary endpoint was the between-group difference (ENTRESTO vs enalapril) from baseline to Week 12 in aortic characteristic impedance (Zc), a measure of central aortic stiffness.9
**PROVE-HF: Primary end point of this study was the correlation between changes in the concentration of NT-proBNP and cardiac remodelling, assessed by change in LVEDVI, LVESVI, LVEF, and LAVI from baseline to 12 months (P<0.01 was achieved for all changes).11
††PIONEER: The ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change was -46.7% vs.-25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71 [95% CI: 0.63-0.81], P<0.001).8
‡‡Primary endpoint: Time-averaged proportional change in NT-proBNP concentration from baseline through Weeks 4 and 8.8
§§TRANSITION: The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint (45.4% vs. 50.7%; risk ratio, 0.90 [95% CI: 0.79-1.02]).10
ACEi, angiotensin converting enzyme inhibitor; ADHF, acute decompensated heart failure; AE, adverse event; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor; BNP, brain natriuretic peptide; CI, confidence interval; CV, cardiovascular; EF, ejection fraction; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; KCCQ, Kansas City Cardiomyopathy Questionnaire; LAVI, left atrial volume index; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction; LVESVI, left ventricular end-systolic volume index; NT-proBNP, N-terminal-pro-brain natriuretic peptide; NYHA, New York Heart Association; QoL, quality of life.
- 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).
- Claggett B, et al. N Engl J Med 2015;373(23):2289–2290.
- Lewis EF, et al. Circ Heart Fail 2017;10(8):e003430.
- McMurray JJ, et al. N Engl J Med 2014;371(11):993–1004.
- Solomon SD, et al. JACC Heart Fail 2016;4(10):816–822.
- Chandra A, et al. JAMA Cardiol 2018;3(6):498–505.
- Velazquez EJ, et al. N Engl J Med 2019;380(6):539–548.
- Desai AS, et al. JAMA 2019;322(11):1077–1084.
- Wachter R, et al. Eur J Heart Fail 2019;21(8):998–1007.
- Januzzi JL Jr, et al. JAMA 2019;322(11):1085–1095.
- Heidenreich PA, et al. Circulation 2022;145:e895–e1032.
- CaReMe UK HF algorithm. Available at: https://www.britishcardiovascularsociety.org/__data/assets/powerpoint_do.... (Accessed May 2023).
- McDonagh TE, et al. Eur Heart J 2021;42(36):3599–3726.
- Gheorghiade M, et al. Am J Cardiol 2005;96(6A):11G–17G.
- Welsh HF Expert Reference Group 2021. HF in Wales in 2021 – a Parallel Approach.
- Heart Failure Hub Scotland guidelines. Available at: https://www.heartfailurehubscotland.co.uk/wp-content/uploads/2020/03/NHS.... (Accessed May 2023).
- DeVore AD, et al. Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: results of the open-label extension of the PIONEER-HF trial. Data presented at American College of Cardiology 68th Annual Scientific Session, March 2019.
- Morrow DA, et al. Circulation 2019;139(19):2285–2288.