Skip to main content

Important Safety Information


  • When pregnancy is detected, discontinue ENTRESTO as soon as possible
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus

ENTRESTO is contraindicated in patients with hypersensitivity to any component...


ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.

LVEF is a variable measure, so use clinical judgment in deciding whom to treat.


ACEi, angiotensin-converting enzyme inhibitor; ADHF, acute decompensated heart failure; ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; ARR, absolute risk reduction; BID, twice daily; BNP, brain natriuretic peptide; CI, confidence interval; HR, hazard ratio; KM, Kaplan–Meier; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; NNT, number needed to treat; NYHA, New York Heart Association; OR, odds ratio; RR, relative reduction; RRR, relative risk reduction; SD, standard deviation; SBP, systolic blood pressure.

1. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
2. McMurray JJV, Packer M, Desai AS, et al; on behalf of the PARADIGM-HF Committees Investigators. Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). Eur J Heart Fail. 2014;16(7):817-825. doi:10.1002/ejhf
3. Kristensen SL, Martinez F, Jhund PS, et al. Geographic variations in the PARADIGM-HF heart failure trial. Eur Heart J. 2016;37(41):3167-3174. Nov 1;37(41):3167-3174. doi:10.1093/eurheartj/ehw226
4. Data on file. LCZ696 Clinical Study Report (CLCZ696B2314). Novartis Pharmaceuticals Corp; 2014.
5. Zile MR, Clagget BL, Prescott MF, et al. Prognostic implications of changes in N-terminal pro-B-type natriuretic peptide in patients with heart failure. J Am Coll Cardiol. 2016;68(22):2425-2436. doi:10.1016/j.jacc.2016.09.931
6. Desai AS, McMurray JJ, Packer M, et al. Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J. 2015;36(30):1990-1997. doi:10.1093/eurheartj/ehv186
7. Velazquez EJ, Morrow DA, DeVore AD, et al; for the PIONEER-HF Investigators. Angiotensin–receptor-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380(6):539-548. doi:10.1056/NEJMoa1812851
8. Morrow DA, Velazquez EJ, DeVore AD, et al. Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF trial. Circulation. 2019;139(19):2285-2288. doi:10.1161/CIRCULATIONAHA.118.039331
9. Bettencourt P, Azevedo A, Pimenta J, et al. N-terminal–pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation. 2004;110(15):2168-2174. doi:10.1161/01.CIR.0000144310.04433.BE
10. DeVore AD, Braunwald E, Morrow DA, et al; PIONEER-HF Investigators. Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: secondary analysis of the open-label extension of the PIONEER-HF trial. JAMA Cardiol. 2020;5(2):202-207. doi:10.1001/jamacardio.2019.4665. Accessed December 12, 2019. Supplementary material accessed at
11. Albert N, Bena J, Morrison S, et al. Clinical outcomes when utilizing sacubitril/valsartan vs. ACEi/ARB in patients with HF and ejection fractions spanning from reduced to preserved—a retrospective, parallel, multi-group study. Paper presented at: Heart Failure Society of America. September 10-13, 2021.
12. US Food and Drug Administration. Novartis cardiovascular and renal drugs advisory committee briefing document, December 15, 2020. ENTRESTO® (sacubitril/valsartan) for chronic heart failure and preserved ejection fraction. Accessed October 3, 2023.