Efficacy and Safety of Sacubitril/Valsartan in the Management of Heart Failure with Preserved Ejection Fraction: A Comprehensive Review
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Abstract
Heart failure with preserved ejection fraction (HFpEF) represents a significant clinical challenge due to its complex pathophysiology, limited therapeutic options, and growing prevalence, particularly in aging populations. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), has emerged as a potential therapeutic intervention in HFpEF. While sacubitril/valsartan has demonstrated substantial benefits in heart failure with reduced ejection fraction (HFrEF), its role in HFpEF has been the subject of extensive clinical investigations. This review aims to evaluate the efficacy, safety, and clinical implications of sacubitril/valsartan in the treatment of HFpEF. We will discuss the pharmacological mechanisms of the ARNI combination, key clinical trials, and their outcomes, including the PARAGON-HF trial, and assess its impact on morbidity, mortality, functional status, and quality of life in HFpEF patients. Additionally, we will explore potential biomarkers for response to therapy and the relevance of phenotyping HFpEF subgroups to optimize therapeutic strategies.
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References
I. Metra M, Teerlink JR. Heart failure. Lancet. (2017) 390:1981–95. 10.1016/S0140-6736(17)31071-1
II. Gazewood JD, Turner PL. Heart failure with preserved ejection fraction: diagnosis and management. Am Fam Physician. (2017) 96:582–8. 10.1016/j.amjmed.2016.12.031
III. Ma C, Luo H, Fan L, Liu X, Gao C. Heart failure with preserved ejection fraction: an update on pathophysiology, diagnosis, treatment, and prognosis. Braz J Med Biol Res. (2020) 53:e9646. 10.1590/1414-431x20209646
IV. Gu J, Noe A, Chandra P, Al-Fayoumi S, Ligueros-Saylan M, Sarangapani R, et al. . Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. (2010) 50:401–14. 10.1177/0091270009343932
V. Gori M, D'Elia E, Senni M. Sacubitril/valsartan therapeutic strategy in HFpEF: clinical insights and perspectives. Int J Cardiol. (2019) 281:158–65. 10.1016/j.ijcard.2018.06.060
VI. Kuno T, Ueyama H, Fujisaki T, Briasouli A, Takagi H, Briasoulis A. Meta-analysis evaluating the effects of renin-angiotensin-aldosterone system blockade on outcomes of heart failure with preserved ejection fraction. Am J Cardiol. (2020) 125:1187–93. 10.1016/j.amjcard.2020.01.009
VII. Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, et al. . Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. (2019) 381:1609–20. 10.1056/NEJMoa1908655
VIII. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. (2009) 6:e1000097. 10.1371/journal.pmed.1000097
IX. Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, et al. . The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. (2012) 380:1387–95. 10.1016/S0140-6736(12)61227-6
X. Maries L, Manitiu I. Diagnostic and prognostic values of B-type natriuretic peptides (BNP) and N-terminal fragment brain natriuretic peptides (NT-pro-BNP). Cardiovasc J Afr. (2013) 24:286–9. 10.5830/CVJA-2013-055
XI. Cocco G, Jerie P. Assessing the benefits of natriuretic peptides-guided therapy in chronic heart failure. Cardiol J. (2015) 22:5–11. 10.5603/CJ.a2014.0041
XII. Shah SJ, Katz DH, Selvaraj S, Burke MA, Yancy CW, Gheorghiade M, et al. . Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. (2015) 131:269–79. 10.1161/CIRCULATIONAHA.114.010637
XIII. Pieske B, Wachter R, Shah SJ, Baldridge A, Szeczoedy P, Ibram G, 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) 326:1919–29. 10.1001/jama.2021.18463
XIV. Thomas L, Marwick TH, Popescu BA, Donal E, Badano LP. Left atrial structure and function, and left ventricular diastolic dysfunction: JACC state-of-the-art review. J Am Coll Cardiol. (2019) 73:1961–77. 10.1016/j.jacc.2019.01.059
XV. Solomon SD, Rizkala AR, Gong J, Wang W, Anand IS, Ge J, et al. . Angiotensin receptor neprilysin inhibition in heart failure with preserved ejection fraction: rationale and design of the PARAGON-HF trial. JACC Heart Fail. (2017) 5:471–82. 10.1016/j.jchf.2017.04.013
XVI. Del Buono MG, Bonaventura A, Vecchie A, Wohlford GF, Dixon DL, Van Tassel BW, et al. . Sacubitril–valsartan for the treatment of heart failure: time for a paragon? J Cardiovasc Pharmacol. (2020) 75:105–7. 10.1097/FJC.0000000000000782
XVII. Del Buono MG, Iannaccone G, Scacciavillani R, Carbone S, Camilli M, Niccoli G, et al. . Heart failure with preserved ejection fraction diagnosis and treatment: an updated review of the evidence. Prog Cardiovasc Dis. (2020) 63:570–84. 10.1016/j.pcad.2020.04.011