Contents

Search

sacubitril/valsartan (Entresto)

Indications: - systolic heart failure [1,2,3,7]* - reduces 30 day readmission after heart failure hospitalization relative to enalopril (9.7 vs 13.4% for heart failure-specific readmission) [4] - cost-effective vs lisinopril for NYHA class 2-4 heart failure [5] - may be initiated in patients with new onset systolic heart failure without prior trial of ACE inhibitor or ARB [15] - reduces cardiovascular & renal events in patients with mild HFrEF or HFpEF [16] * improves cardiovascular & all-cause mortality vs enalopril [7] * number needed to treat to prevent 1 cardiovascular death = 32 * improves physical & social activities [7] * improves sexual function vs enalapril [7] Contraindications: - diastolic heart failure [9,11,12] - decreases serum NT-proBNP at 12 weeks, but not submaximal exercise tolerance at 24 weeks [12] Dosage: - 200 mg twice daily [7] - sacubiril 49 mg, valsartan 51 mg Adverse effects: - hypotension - hyperkalemia - renal insufficiency - angioedema [2] - increases serum BNP (but decreases serum NT-proBNP) [8] Drug interactions: - risk for severe hyperkalemia is lower with coadministration of sacubitril/valsartan plus spironolactone than with enalapril plus spironolactone [6] Notes: - FDA-approved July 2015 - direct to consumer advertising as Entresto on television Clinical trials: - PARADIGM-HF: - superior to enalapril for treatment of LV systolic dysfunction & LVEF 25% - lowered serum NT-proBNP -47% vs -15% for enalapril [8] - sacubitril/valsartan no better than ramapril for MI complicated by left ventricular dysfunction or pulmonary congestion [13] - sacubitril/valsartan no better than valsartan for reducing serum NT-proBNP levels in patients with left ventricular systolic dysfunction (HFrEF) [14]

General

angiotensin receptor neprilysin inhibitor (ARNI)

References

  1. McMurray JJV et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014 Aug 30; PMID: 25176015 http://www.nejm.org/doi/full/10.1056/NEJMoa1409077
  2. FDA News Release. July 7, 2015 FDA approves new drug to treat heart failure http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453845.htm
  3. Yancy CW et al Heart Failure Focused Update on Pharmacological Therapy. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation 2016 134: PMID: 27208050 http://circ.ahajournals.org/content/early/2016/05/18/CIR.0000000000000435.full.pdf+html - J Am Coll Cardiol. 2016 May 17. PMID: 27216111 Free Article - Antman EM et al Editorial: ACC/AHA/HFSA and ESC Updated Heart Failure Guideline Collaboration. Updated Clinical Practice Guidelines on Heart Failure: An International Alignment. Circulation 2016 134: PMID: 27216110 Free Article http://circ.ahajournals.org/content/early/2016/05/18/CIR.0000000000000436.full.pdf+html
  4. Desai AS et al Influence of Sacubitril/Valsartan (LCZ696) on 30-Day Readmission After Heart Failure Hospitalization. J Am Coll Cardiol. 2016;68(3):241-248 PMID: 27417000 Free Article http://content.onlinejacc.org/article.aspx?articleid=2532918 - Mentz RJ, O'Brien EC Can 2 Pills a Day Keep Readmission Away? Sacubitril/Valsartan to Reduce 30-Day Heart Failure Readmissions. J Am Coll Cardiol. 2016;68(3):249-251 PMID: 27417001 http://content.onlinejacc.org/article.aspx?articleid=2532923
  5. Sandhu AT, Ollendorf DA, Chapman RH et al Cost-Effectiveness of Sacubitril - Valsartan in Patients With Heart Failure With Reduced Ejection Fraction. Ann Intern Med. Published online 30 August 2016 PMID: 27571284 http://annals.org/article.aspx?articleid=2546543
  6. Desai AS, Vardeny O, Claggett B et al Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/ Valsartan Compared With Enalapril. A Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. Published online November 14, 2016 PMID: 27842179 http://jamanetwork.com/journals/jamacardiology/article-abstract/2583456 - Ezekowitz JA Hyperkalemia, Sacubitril/Valsartan, and Mineralocorticoid Antagonists in Patients With Heart Failure. JAMA Cardiol. Published online November 14, 2016 PMID: 27842180 http://jamanetwork.com/journals/jamacardiology/article-abstract/2583455
  7. Chandra A, Lewis EF, Claggett BL et al Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart FailureA Secondary Analysis of the PARADIGM-HF Trial. JAMA Cardiol. Published online April 4, 2018 PMID: 29617523 https://jamanetwork.com/journals/jamacardiology/fullarticle/2677630
  8. Velazquez EJ, Morrow DA, DeVore AD et al. PIONEER-HF Investigators Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med 2018 Nov 11. PMID: 30415601 https://www.nejm.org/doi/10.1056/NEJMoa1812851
  9. Solomon SD, McMurray JJV, Anand IS et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 2019 Sep 1; PMID: 31475794 https://www.nejm.org/doi/10.1056/NEJMoa1908655
  10. Desai AS, Solomon SD, Shah AM et al. Effect of sacubitril-valsartan vs enalapril on aortic stiffness in patients with heart failure and reduced ejection fraction: A randomized clinical trial. JAMA 2019 Sep 2; PMID: 31475296 https://jamanetwork.com/journals/jama/article-abstract/2749477 - Januzzi JL Jr, Prescott MF, Butler J et al. Association of change in N-terminal pro-B-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA 2019 Sep 2 PMID: 31475295 https://jamanetwork.com/journals/jama/article-abstract/2749476 - Drazner MH. Angiotensin receptor-neprilysin inhibition (ARNI) therapy and reverse remodeling in heart failure with reduced ejection fraction. JAMA 2019 Sep 2; PMID: 31475298 https://jamanetwork.com/journals/jama/article-abstract/2749474
  11. McMurray JJV et al. Effects of sacubitril-valsartan, versus valsartan, in women compared to men with heart failure and preserved ejection fraction: Insights from PARAGON-HF. Circulation 2019 Nov 17; PMID: 31736337 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044491
  12. Pieske B, Wachter R, Shah SJ et al Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction. The PARALLAX Randomized Clinical Trial. JAMA. 2021;326(19):1919-1929. PMID: 34783839 https://jamanetwork.com/journals/jama/fullarticle/2786245 - Redfield MM, Borlaug BA Quality of Life and Exercise Ability in Heart Failure With Preserved Ejection Fraction. No Time for Therapeutic Complacency. JAMA. 2021;326(19):1913-1915 PMID: 34783856 https://jamanetwork.com/journals/jama/fullarticle/2786265
  13. Pfeffer MA, Claggett B, Lewis EF et al. Angiotensin receptor-neprilysin inhibition in acute myocardial infarction. N Engl J Med 2021 Nov 11; 385:1845 PMID: 34758252 https://www.nejm.org/doi/10.1056/NEJMoa2104508
  14. Mann DL, Givertz MM, Vader JM et al Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection FractionA Randomized Clinical Trial. JAMA Cardiol. 2022;7(1):17-25. PMID: 34730769 PMCID: PMC8567189 (available on 2022-11-03) https://jamanetwork.com/journals/jamacardiology/fullarticle/2785700
  15. Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
  16. Vaduganathan M, Mentz RJ, Claggett BL et al Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF. Eur Heart J. 2023 Aug 14;44(31):2982-2993. PMID: 37210743 PMCID: PMC10424880 Free PMC article. Clinical Trial.

Components

sacubitril valsartan (Diovan)