Striking the Right Balance in Heart Failure
Authors: Monica R. Shah, Michael S. Lauer
Journal: Annals of Internal Medicine (2015)

Ideas and Opinions19 January 2016Striking the Right Balance in Heart FailureMonica R. Shah, MD and Michael S. Lauer, MDMonica R. Shah, MDFrom the National Heart, Lung, and Blood Institute, Bethesda, Maryland. and Michael S. Lauer, MDFrom the National Heart, Lung, and Blood Institute, Bethesda, Maryland.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-2587 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The treatment of heart failure with reduced ejection fraction (HFREF) is a fascinating story of our evolving understanding of how to modulate physiologic systems to improve clinical outcomes—and combination therapies, such as sacubitril–valsartan (formerly known as LCZ696), that intervene on multiple systems may be the protagonists of the next chapter. In the late 1980s, we learned that blockade of the renin–angiotensin–aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors significantly decreased morbidity and mortality in HFREF (1, 2). We then discovered that antagonism of the sympathetic nervous system with β-adrenergic–receptor blockers and further inhibition of the RAAS with mineralocorticoid antagonists increased survival ...References1. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293-302. [PMID: 2057034] CrossrefMedlineGoogle Scholar2. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316:1429-35. [PMID: 2883575] CrossrefMedlineGoogle Scholar3. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349-55. [PMID: 8614419] CrossrefMedlineGoogle Scholar4. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709-17. [PMID: 10471456] CrossrefMedlineGoogle Scholar5. Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667-75. [PMID: 11759645] CrossrefMedlineGoogle Scholar6. Braunwald E. The path to an angiotensin receptor antagonist-neprilysin inhibitor in the treatment of heart failure. J Am Coll Cardiol. 2015;65:1029-41. doi:10.1016/j.jacc.2015.01.033 CrossrefMedlineGoogle Scholar7. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004. [PMID: 25176015] doi:10.1056/NEJMoa1409077 CrossrefMedlineGoogle Scholar8. Moe GW, Ezekowitz JA, O'Meara E, Lepage S, Howlett JG, Fremes S, et al; Canadian Cardiovascular Society. The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Focus Update: anemia, biomarkers, and recent therapeutic trial implications. Can J Cardiol. 2015;31:3-16. [PMID: 25532421] doi:10.1016/j.cjca.2014.10.022 CrossrefMedlineGoogle Scholar9. Cheng RK, Cox M, Neely ML, Heidenreich PA, Bhatt DL, Eapen ZJ, et al. Outcomes in patients with heart failure with preserved, borderline, and reduced ejection fraction in the Medicare population. Am Heart J. 2014;168:721-30. [PMID: 25440801] doi:10.1016/j.ahj.2014.07.008 CrossrefMedlineGoogle Scholar10. Vodovar N, Séronde MF, Laribi S, Gayat E, Lassus J, Januzzi JL, et al; GREAT Network. Elevated plasma B-type natriuretic peptide concentrations directly inhibit circulating neprilysin activity in heart failure. JACC Heart Fail. 2015;3:629-36. [PMID: 26251090] doi:10.1016/j.jchf.2015.03.011 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From the National Heart, Lung, and Blood Institute, Bethesda, Maryland.Disclaimer: The opinions expressed here are those of the authors and do not reflect the official positions or opinions of the National Heart, Lung, and Blood Institute or the National Institutes of Health.Acknowledgment: The authors thank Dr. Eugene Braunwald for his helpful review and comments.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-2587.Corresponding Author: Monica R. Shah, MD, Division of Cardiovascular Sciences of the National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Room 8174, Bethesda, MD 20892-7956; e-mail, [email protected]nih.gov.Current Author Addresses: Dr. Shah: Division of Cardiovascular Sciences of the National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Room 8174, Bethesda, MD 20892-7956.Dr. Lauer: National Institutes of Health, 1 Center Drive, Building 1, Room 144, Bethesda, MD 20814.Author Contributions: Conception and design: M.R. Shah, M.S. Lauer.Drafting of the article: M.R. Shah, M.S. Lauer.Critical revision of the article for important intellectual content: M.S. Lauer.Final approval of the article: M.R. Shah, M.S. Lauer.This article was published at www.annals.org on 22 December 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCost-Effectiveness of Sacubitril–Valsartan in Patients With Heart Failure With Reduced Ejection FractionAlexander T. Sandhu, MD, MS, Daniel A. Ollendorf, PhD, Richard H. Chapman, PhD, Steven D. Pearson, MD, MSc, and Paul A. Heidenreich, MD, MSAngioedema with renin angiotensin system drugs and neutral endopeptidase inhibitorsUnbelievable Folly of Clinical Trials in Heart Failure 19 January 2016Volume 164, Issue 2Page: 125-126KeywordsAngiotensin converting enzyme inhibitorForecastingHeartHeart failureHospitalizationsLungsMorbidityMortalityNatriuretic peptidesSympathetic nervous system ePublished: 22 December 2015 Issue Published: 19 January 2016 PDF downloadLoading ...