sacubitril/valsartan (Entresto)
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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]
- has not been studied in patients without heart failure symptoms (MKSAP20)[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
- asymptomatic heart failure (MKSAP20)[15]
- diastolic heart failure[9][11][12]
- decreases serum NT-proBNP at 12 weeks, but not submaximal exercise tolerance at 24 weeks[12]
- not useful for treatment of hypertension[15]
- sacubitril is contraindicated in patients with a history of angioedema[15]
- avoid in patients with hypotension
Dosage
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]
- avoid use in combination with ACE inhibitor or other ARB
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]
- superior to enalapril for treatment of LV systolic dysfunction & LVEF 25%
- sacubitril/valsartan no better than valsartan for reducing serum NT-proBNP levels in patients with left ventricular systolic dysfunction (HFrEF)[14]
Notes
- FDA-approved July 2015
- direct to consumer advertising as Entresto on television
More general terms
Components
References
- ↑ 1.0 1.1 McMurray JJV et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014 Aug 30; <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/25176015 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1409077
- ↑ 2.0 2.1 2.2 FDA News Release. July 7, 2015 FDA approves new drug to treat heart failure http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453845.htm
- ↑ 3.0 3.1 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: <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27208050 <Internet> http://circ.ahajournals.org/content/early/2016/05/18/CIR.0000000000000435.full.pdf+html
J Am Coll Cardiol. 2016 May 17. PMID: https://pubmed.ncbi.nlm.nih.gov/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: <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27216110 Free Article <Internet> http://circ.ahajournals.org/content/early/2016/05/18/CIR.0000000000000436.full.pdf+html - ↑ 4.0 4.1 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 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27417000 Free Article <Internet> 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 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27417001 <Internet> http://content.onlinejacc.org/article.aspx?articleid=2532923 - ↑ 5.0 5.1 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 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27571284 <Internet> http://annals.org/article.aspx?articleid=2546543
- ↑ 6.0 6.1 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 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27842179 <Internet> 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 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27842180 <Internet> http://jamanetwork.com/journals/jamacardiology/article-abstract/2583455 - ↑ 7.0 7.1 7.2 7.3 7.4 7.5 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: https://pubmed.ncbi.nlm.nih.gov/29617523 https://jamanetwork.com/journals/jamacardiology/fullarticle/2677630
- ↑ 8.0 8.1 8.2 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: https://pubmed.ncbi.nlm.nih.gov/30415601 https://www.nejm.org/doi/10.1056/NEJMoa1812851
- ↑ 9.0 9.1 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: https://pubmed.ncbi.nlm.nih.gov/31475794 https://www.nejm.org/doi/10.1056/NEJMoa1908655
- ↑ 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: https://pubmed.ncbi.nlm.nih.gov/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: https://pubmed.ncbi.nlm.nih.gov/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: https://pubmed.ncbi.nlm.nih.gov/31475298 https://jamanetwork.com/journals/jama/article-abstract/2749474 - ↑ 11.0 11.1 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: https://pubmed.ncbi.nlm.nih.gov/31736337 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044491
- ↑ 12.0 12.1 12.2 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: https://pubmed.ncbi.nlm.nih.gov/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: https://pubmed.ncbi.nlm.nih.gov/34783856 https://jamanetwork.com/journals/jama/fullarticle/2786265 - ↑ 13.0 13.1 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: https://pubmed.ncbi.nlm.nih.gov/34758252 https://www.nejm.org/doi/10.1056/NEJMoa2104508
- ↑ 14.0 14.1 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: https://pubmed.ncbi.nlm.nih.gov/34730769 PMCID: PMC8567189 (available on 2022-11-03) https://jamanetwork.com/journals/jamacardiology/fullarticle/2785700
- ↑ 15.0 15.1 15.2 15.3 15.4 15.5 Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025 - ↑ 16.0 16.1 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: https://pubmed.ncbi.nlm.nih.gov/37210743 PMCID: PMC10424880 Free PMC article. Clinical Trial.