ENTRESTO is indicated in adult patients for the treatment of symptomatic chronic heart failure with reduced ejection fraction.1,2
Start Entresto today to help your chronic HFrEF patients improve their quality of life vs ACEi (enalapril)*†3–6
Most patients with heart failure report limitations in their daily activities due to physical symptoms such as dyspnoea, fatigue, oedema, sleeping difficulties and chest pain.7
Based on a secondary analysis of PARADIGM-HF, starting ENTRESTO can lead to substantial improvements in social and physical activities vs ACEi (enalapril):‡3
Hobbies & recreation
Patients on ENTRESTO experienced improved QoL, reduced hospitalisations and decreased mortality vs ACEi (enalapril)§4
greater improvement in HRQoL as measured by KCCQ¶ overall summary score was experienced by patients taking ENTRESTO vs enalapril‖4
HRQoL improvements when taking ENTRESTO vs enalapril, detectable by 4 months after randomisation and sustained throughout 36 months4
Starting ENTRESTO first-line can add up to 2 years to patients’ lives vs ACEi3,4,6
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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
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).
*PARADIGM-HF was a multinational, randomised, double-blind trial comparing ENTRESTO to enalapril in 8,442 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 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.6 In a post-hoc analysis of PARADIGM-HF (n=7618), 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).1
‡As measured by an analysis model that incorporated age and treatment effect. This analysis model was included in a secondary analysis of PARADIGM-HF* that examined the effect of ENTRESTO on components of the physical and social limitation section of the KCCQ at 8 months, and longitudinally over 36 months. Patients in the ENTRESTO group had significantly better adjusted change scores in 7 out of 10 physical and social activities vs the enalapril group. 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).3
§Post hoc analysis of PARADIGM-HF that examined the changes in KCCQ scores at randomisation, Month 4, Month 8, Month 12, and annually thereafter through final visit. 91% of patients enrolled in PARADIGM-HF (n=7,623/8,399) completed the KCCQ at randomisation, with complete data at 8 months for 6,881 patients (90% of baseline). At Month 8, the ENTRESTO group noted improvements in both KCCQ clinical summary score (+0.64 vs −0.29; P=0.008) and KCCQ overall summary score (+1.13 vs −0.14; P<0.001) in comparison to the enalapril group, as well as a significantly smaller proportion of patients with deterioration (≤5 points decrease) of both KCCQ scores (27% vs 31%; P=0.01). Adjusted change scores demonstrated consistent improvements in ENTRESTO vs enalapril through 36 months. Patients who died or did not complete the 8-month KCCQ score were excluded from the principal analysis.4
¶KCCQ is a self-administered, health-related, QoL measure for HF patients that quantifies physical function, symptoms, social function, self-efficacy and knowledge, and QoL on a scale of 0–100, with higher scores indicating fewer symptoms and physical limitations associated with HF. 7,618 of 8,399 patients from the PARADIGM-HF trial completed the initial KCCQ assessment.4
‖LSM estimation (SE) ENTRESTO vs enalapril: 0.80 (20) vs −0.39 (−0.20). LSM estimates (SE) difference: 1.19 (0.28), P<0.001.4
ACEi, angiotensin-converting enzyme inhibitor; AE, adverse event; CI, confidence interval; CV, cardiovascular; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFSN, heart failure specialist nurse; HRQoL, health-related quality of life; KCCQ, Kansas City Cardiomyopathy Questionnaire; LSM, least squares mean; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; QoL, quality of life; SE, standard error.
- 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).
- Chandra A, et al. JAMA Cardiol 2018;3(6):498–505.
- Lewis EF, et al. Circ Heart Fail 2017;10(8):e003430.
- McMurray JJ, et al. N Engl J Med 2014;371(11):993–1004.
- Claggett B, et al. N Engl J Med 2015;373(23):2289–2290.
- Heo S, et al. Heart Lung 2009;38(2):100–108.
- CaReMe UK HF algorithm. Available at: https://www.britishcardiovascularsociety.org/__data/assets/powerpoint_do.... (Accessed May 2023).
- Maddox TM, et al. J Am Coll Cardiol 2021;77(6):772–810.
- 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).
- McDonagh TE, et al. Eur Heart J 2021;42(36):3599–3726.