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
Starting and monitoring patients on ENTRESTO is as simple as with ACEi (enalapril)1–3
Flexible starting doses tailored to your patients’ needs, with titration similar to ACEi (enalapril):1–3
ENTRESTO 24/26 mg
ENTRESTO 49/51 mg
ENTRESTO 97/103 mg
The starting dose is 24/26 mg or 49/51 mg twice daily, depending on the patient’s current treatment and medical condition1,2
The target dose is 97/103 mg twice daily1,2
ENTRESTO contains valsartan and therefore should not be co-administered with another ARB-containing product.
Stop using an ACEi for at least 36 hours before starting ENTRESTO1,2
Prescribe ENTRESTO as your first choice with confidence1,2
In clinical trials, ENTRESTO generally demonstrated comparable safety and efficacy to ACEi (enalapril)1,2,4,5
PARADIGM-HF:* Most commonly reported AEs with ENTRESTO were hypotension, hyperkalaemia and renal impairment1,2,4
- Fewer patients taking ENTRESTO discontinued therapy due to an AE during the double-blind period: 10.7% vs 12.3% with enalapril4
- While more patients experienced symptomatic hypotension with ENTRESTO than with ACEi (enalapril), there was no increase in the rate of discontinuation due to hypotension-related effects (0.9% vs 0.7%; P=0.38)4
PIONEER-HF:†
- 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‡5
Download the ENTRESTO clinical trial summaries for more information
§eGFR, urea, creatinine.
¶E.g. potassium, sodium.
If patients experience tolerability issues (systolic blood pressure [SBP] ≤95 mmHg, symptomatic hypotension, hyperkalaemia, renal dysfunction), adjustment of concomitant medicinal products, temporary down–titration or discontinuation of Entresto is recommended.
Dosing considerations:1,2
| Standard dosing (49/51 mg twice daily) is indicated for patients: | Low dosing (24/26 mg twice daily) is indicated for patients: |
| On a prior high dose of ACEi/ARBs | Not receiving prior therapy with ACEi/ARB or on a low dose of ACEi/ARB |
| With mild renal impairment | With moderate/severe renal impairment‖ |
| With mild liver impairment | With SBP ≥100 to 110 mmHg |
| With moderate liver impairment or with AST/ALT values more than twice the ULN** |
‖Entresto was not recommended in patients with end-stage renal disease and concomitant use with aliskiren‐containing medicinal products in patients with diabetes mellitus or in patients with renal impairment (eGFR <60 ml/min/1.73 m2) was contraindicated. Use with caution in patients with severe renal impairment (eGFR <30 mL/min/1.73 m2).1,2
**Moderate hepatic impairment: Child-Pugh B classification. Use with caution in these patients. ENTRESTO is contraindicated in patients with severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C classification).1,2
The use of ENTRESTO may cause…
HYPOTENSION:
Temporary down-titration or discontinuation recommended. Consider other causes of hypotension††1,2
RENAL FUNCTION:
Consider down-titration in clinically relevant cases1,2
HYPERKALAEMIA:
Adjustment of concomitant medicinal products, temporary down-titration or discontinuation recommended. If serum K+ >5.4 mmol/L discontinuation should be considered1,2
ANGIOEDEMA:
Immediate discontinuation. Provide appropriate therapy and monitoring until resolution. ENTRESTO must not be readministered1,2
Known history of angioedema related to previous ACE inhibitor or ARB therapy and hereditary or idiopathic angioedema are contraindicated in ENTRESTO.
Do not initiate ENTRESTO in patients with SBP <100 mmHg or serum K+ levels >5.4 mmol/L1,2
Stop using an ACEi for 36 hours before starting ENTRESTO1,2
††Dose adjustment of diuretics, concomitant antihypertensives and treatment of other causes of hypotension should be considered.
Newly diagnosed chronic HFrEF patient
‡‡Monitoring of serum potassium is recommended, especially in patients who have risk factors such as renal impairment, diabetes mellitus or hypoaldosteronism or who are on a high potassium diet or on mineralocorticoid antagonist.
§§An ACEi should be stopped for 36 hours before starting ENTRESTO.1,2
¶¶In vitro data indicate that sacubitril inhibits OATP1B1 and OATP1B3 transporters. ENTRESTO may therefore increase the systemic exposure of OATP1B1 and OATP1B3 substrates such as statins.1–3
‖‖Co-administration of nitroglycerin and sacubitril/valsartan was associated with a treatment difference of 5 bpm in heart rate compared to the administration of nitroglycerine alone. A similar effect on the heart rate may occur when sacubitril/valsartan is co-administered with sublingual, oral or transdermal nitrates. In general, no dose adjustment is required.1–3
Learn more about how ENTRESTO can be used as your first choice in place of ACEi/ARB wherever your patients are in their HF journey1,2,4–14
Please click here for safety information
*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.4
†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 NTproBNP ≥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.5
‡Primary endpoint: Time-averaged proportional change in NT-proBNP concentration from baseline through Weeks 4 and 8.5
ACEi, angiotensin-converting enzyme inhibitor; ADHF, acute decompensated heart failure; AE, adverse event; ALT, alanine aminotransferase; ARB, angiotensin receptor blocker; AST, aspartate aminotransferase; CV, cardiovascular; EF, ejection fraction; eGFR, estimated glomerular filtration rate; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; K+, potassium; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal-pro-brain natriuretic peptide; NYHA, New York Heart Association; SBP, systolic blood pressure; ULN, upper limit of normal.
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).
- Enalapril Summary of Product Characteristics. Electronic medicines compendium website, UK. Available at: https://www.medicines.org.uk/emc/product/561/smpc. (Accessed May 2023).
- McMurray JJ, et al. N Engl J Med 2014;371:993–1004.
- Velazquez EJ, et al. N Engl J Med 2019;380(6):539–548.
- Claggett B, et al. N Engl J Med 2015;373(23):2289–2290.
- Lewis EF, et al. Circ Heart Fail 2017;10(8):e003430.
- Solomon SD, et al. JACC Heart Fail 2016;4(10):816–822.
- Chandra A, et al. JAMA Cardiol 2018;3(6):498–505.
- 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).