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Important Safety Information

BOXED WARNING: FETAL TOXICITY

  • 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...

Indication

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.

Click or scroll to see IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING AND INDICATION

Definitions
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; ARR, absolute rate reduction; BID, twice daily; BMI, body mass index; CI, confidence interval; ED, emergency department; eGFR, estimated glomerular filtration rate; HFmrEF, heart failure with mildly reduced ejection fraction; HR, hazard ratio; IV, intravenous; LAE, left atrial enlargement; LVH, left ventricular hypertrophy; MRA, mineralocorticoid receptor antagonist; NS, not significant; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; NYHA, New York Heart Association; OR, odds ratio; RASi, renin–angiotensin system inhibitor; RR, rate reduction; RRR, relative rate reduction.

References
1. Vaduganathan M, Claggett BL, Greene SJ, et al. Potential implications of expanded US food and drug administration labeling for sacubitril/valsartan in the US. JAMA Cardiol. Published online September 15, 2021. doi:10.1001/jamacardio.2021.3651
2. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp. 
3. 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 May 3, 2023. https://www.fda.gov/media/144379/download
4. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381(17):1609-1620. doi:10.1056/NEJMoa1908655
5. Mentz RJ, Ward JH, Hernandez AF, et al. Angiotensin-neprilysin inhibition in patients with mildly reduced or preserved ejection fraction and worsening heart failure. J Am Coll Cardiol. 2023;S0735-1097(23)05429-3. doi:10.1016/j.jacc.2023.04.019 
6. Mentz RJ, Ward JH, Hernandez AF, et al. Rationale, design and baseline characteristics of the PARAGLIDE-HF trial: sacubitril/valsartan vs valsartan in HFmrEF and HFpEF with a worsening heart failure event [published online ahead of print, February 14, 2023]. J Card Fail. 2023;S1071-9164(23)00040-4. doi:10.1016/j.cardfail.2023.02.001 
7. Data on file. Study CLCZ696DUS01. Novartis Pharmaceuticals Corp; 2023. 
8. Mentz RJ, Ward JH, Hernandez AF, et al. Angiotensin-neprilysin inhibition in patients with mildly reduced or preserved ejection fraction and worsening heart failure. J Am Coll Cardiol. 2023;S0735-1097(suppl)05429-3. doi:10.1016/j.jacc.2023.04.019 
9. Bettencourt P, Azevedo A, Pimenta J, Friões F, Ferreira S, Ferreira A. 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. Powell-Wiley TM, Ngwa J, Kebede S, et al. Impact of body mass index on heart failure by race/ethnicity from the Get With The Guidelines-Heart Failure (GWTG-HF) registry. JACC Heart Fail. 2018;6(3):233-242. doi:10.1016/j.jchf.2017.11.011 
11. Kumar V, Redfield MM, Glasgow A, et al. Incident heart failure with mildly reduced ejection fraction: frequency, characteristics, and outcomes. J Card Fail. 2023;29(2):124-134. doi:10.1016/j.cardfail.2022.10.424
12. Data on file. Study CLCZ696DUS01. Novartis Pharmaceuticals Corp; 2021.