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Angiotensin Receptor Neprilysin Inhibitors—2019 Update

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Abstract

An abundance of new data regarding the use of the novel drug compound sacubitril/valsartan in chronic heart failure (CHF) patients is published every year since the initial publication of the PARADIGM-HF study in 2014. This review summarises the most recent evidence (2019 and onwards) of sacubitril/valsartan in CHF patients as well as provides a critical appraisal of these data. New data are grouped in categories such as real-world data, randomised controlled trials, surrogate end-points, cost-effectiveness, use of sacubitril/valsartan as an anti-hypertensive treatment, effect on diuretic dosing and implementation of this novel compound in other populations. This review of recent literature identified important messages such as early initiation during index hospitalisation or immediately post-discharge, barriers against implementation of this novel treatment modality, analytical issues regarding measuring natriuretic peptides in patients under treatment and extrapolated use of sacubitril/valsartan in other than PARADIGM-HF populations. This update may serve as a very helpful evidence-based resource for practising clinicians, future research planning and health-related policy makers.

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References

  1. Entresto. 2015. https://www.ema.europa.eu/en/documents/overview/entresto-epar-summary-public_en.pdf. Accessed 20 Mar 2020.

  2. Fabris E, Merlo M, Rapezzi C, et al. Sacubitril/valsartan: updates and clinical evidence for a disease-modifying approach. Drugs. 2019;79:1543–56.

    PubMed  Google Scholar 

  3. Smith KR, Hsu CC, Berei TJ, et al. PARADIGM-HF Trial: secondary analyses address unanswered questions. Pharmacotherapy. 2018;38:284–98.

    PubMed  Google Scholar 

  4. Carballo D, Stirnemann J, Garin N, Marti C, Serratrice J, Carballo S. Eligibility for sacubitril-valsartan in patients with acute decompensated heart failure. ESC Heart Fail. 2020;7(3):1282–1290.

  5. Nordberg-Backelin C, Fu M, Ljungman C. Early experience of sacubitril-valsartan in heart failure with reduced ejection fraction in real-world clinical setting. ESC Heart Fail. 2020;7(3):1049–1055.

  6. de Frutos F, Mirabet S, Ortega-Paz L, et al. Management of heart failure with reduced ejection fraction after ESC 2016 Heart Failure Guidelines: The Linx Registry. ESC Heart Fail. 2020;7:25–35.

    PubMed  PubMed Central  Google Scholar 

  7. Nandal S, Chow CL, Hannah V, Vaddadi G, Van Gaal W. Tolerability and efficacy of sacubitril/valsartan in clinical practice. Intern Med J. 2020. https://doi.org/10.1111/imj.14749.

  8. Pharithi RB, Ferre-Vallverdu M, Maisel AS, et al. Sacubitril-Valsartan in a routine community population: attention to volume status critical to achieving target dose. ESC Heart Fail. 2020;7:158–66.

    PubMed  PubMed Central  Google Scholar 

  9. Esteban-Fernández A, Díez-Villanueva P, Vicent L, et al. Sacubitril/valsartan is useful and safe in elderly people with heart failure and reduced ejection fraction. Data from a real-word cohort. Rev Esp Geriatr Gerontol. 2020;55:65–9.

    PubMed  Google Scholar 

  10. Tan NY, Sangaralingham LR, Sangaralingham SJ, Yao X, Shah ND, Dunlay SM. Comparative effectiveness of sacubitril-valsartan versus ACE/ARB therapy in heart failure with reduced ejection fraction. JACC Heart Fail. 2020;8:43–54.

    PubMed  Google Scholar 

  11. Chen X, Schaufelberger M, Fu M. The eligible population of the PARADIGM-HF trial in a real-world outpatient clinic and its cardiovascular risk between 2005 and 2016. J Cardiovasc Med (Hagerstown). 2020;21:6–12.

    CAS  Google Scholar 

  12. Norberg H, Bergdahl E, Lindmark K. Safety and tolerability of initiating maximum-dose sacubitril-valsartan in patients on target dose renin-angiotensin system inhibitors. Cardiovasc Ther. 2019;2019:6745074.

    PubMed  PubMed Central  Google Scholar 

  13. Miró Ò, Martín-Sánchez FJ, Jacob J, Herrero-Puente P, Gil V, Llorens P. Grupo de Investigación ICA-SEMES Sacubitril/valsartan-treated patients with exacerbated acute heart failure: approaches to care in the emergency department and on the ward. Emergencias. 2019;31:407–12.

    PubMed  Google Scholar 

  14. Mohanty AF, Levitan EB, Dodson JA, et al. Characteristics and healthcare utilization among veterans treated for heart failure with reduced ejection fraction who switched to sacubitril/valsartan. Circ Heart Fail. 2019;12(11):e005691.

    PubMed  Google Scholar 

  15. López-Azor JC, Vicent L, Valero-Masa MJ, et al. Safety of sacubitril/valsartan initiated during hospitalization: data from a non-selected cohort. ESC Heart Fail. 2019;6:1161–6.

    PubMed  PubMed Central  Google Scholar 

  16. Martens P, Verluyten L, Van de Broek H, et al. Determinants of maximal dose titration of sacubitril/valsartan in clinical practice. Acta Cardiol. 2019;7:1–10.

    Google Scholar 

  17. Akerman CC, Beavers JC. Risk factors for intolerance of inpatient sacubitril/valsartan initiation. J Pharm Pract. 2019;897190019878948. https://doi.org/10.1177/0897190019878948.

  18. Jorsal A, Pryds K, McMurray JJV, et al. Optimizing heart failure treatment following cardiac resynchronization therapy. Clin Res Cardiol. 2020;109(5):638–645.

  19. Hsiao FC, Wang CL, Chang PC, Lu YY, Huang CY, Chu PH. Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: real-world experience from Taiwan. J Cardiovasc Pharmacol Ther. 2020;25:152–7.

    PubMed  Google Scholar 

  20. Han J, Chung F, Nguyen QL, Mody FV, Jackevicius CA. Evaluation of patients with heart failure to determine eligibility for treatment with sacubitril/valsartan: insights from a Veterans Administration Healthcare System. Pharmacotherapy. 2019;39:1053–9.

    CAS  PubMed  Google Scholar 

  21. Kapelios CJ, Lainscak M, Savarese G, et al. Heart Failure Long-Term Registry Investigators. Sacubitril/valsartan eligibility and outcomes in the ESC-EORP-HFA Heart Failure Long-Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM-HF trial, ESC guidelines, and real world. Eur J Heart Fail. 2019;21:1383–97.

    CAS  PubMed  Google Scholar 

  22. Atallah B, Sadik ZG, Hisham M, et al. A per-protocol initiation of sacubitril/valsartan in an advanced heart failure disease management programme in the Middle East Gulf Region. ESC Heart Fail. 2019;6:758–63.

    PubMed  PubMed Central  Google Scholar 

  23. Wachter R, Fonseca AF, Balas B, et al. Real-world treatment patterns of sacubitril/valsartan: a longitudinal cohort study in Germany. Eur J Heart Fail. 2019;21:588–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Adie S, Bitar A, Hanigan S, Pogue K, Koelling T, Dorsch M. Real-world prevalence of adverse events after initiating sacubitril/valsartan compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in systolic heart failure. J Card Fail. 2019;25:412–3.

    PubMed  Google Scholar 

  25. Simpson J, Benson L, Jhund PS, Dahlström U, McMurray JJV, Lund LH. “Real world” eligibility for sacubitril/valsartan in unselected heart failure patients: data from the Swedish Heart Failure Registry. Cardiovasc Drugs Ther. 2019;33:315–22.

    PubMed  PubMed Central  Google Scholar 

  26. Parisi C, De Giusti M, Castello L, Dito E, Proietti F, Tomai F. Sacubitril/valsartan: preliminary experience in post-acute stabilized patients with reduced ejection fraction heart failure. Curr Med Res Opin. 2019;35(sup1):17–20.

    CAS  PubMed  Google Scholar 

  27. Pinto G, Tondi L, Gemma M, et al. Real-life indications to sacubitril/valsartan treatment in patients with chronic systolic heart failure. J Cardiovasc Pharmacol. 2019;73:301–6.

    CAS  PubMed  Google Scholar 

  28. Daly A, Coughlan JJ, Mross T, Wafer M, O’Connor A, Liston R. Assessing suitability for sacubitril-valsartan therapy in an Irish cohort: challenges and opportunities. Ir J Med Sci. 2019;188:1169–74.

    PubMed  Google Scholar 

  29. Luo N, Lippmann SJ, Mentz RJ, et al. Relationship between hospital characteristics and early adoption of angiotensin-receptor/neprilysin inhibitor among eligible patients hospitalized for heart failure. J Am Heart Assoc. 2019;8(3):e010484.

    PubMed  PubMed Central  Google Scholar 

  30. Vicent L, Esteban-Fernández A, Gómez-Bueno M, De-Juan J, et al. Sacubitril/valsartan in daily clinical practice: data from a prospective registry. J Cardiovasc Pharmacol. 2019;73:118–24.

    CAS  PubMed  Google Scholar 

  31. Du AX, Westerhout CM, McAlister FA, et al. Titration and tolerability of sacubitril/valsartan for patients with heart failure in clinical practice. J Cardiovasc Pharmacol. 2019;73:149–54.

    CAS  PubMed  Google Scholar 

  32. Martens P, Lambeets S, Lau CW, Dupont M, Mullens W. Impact of sacubitril/valsartan on heart failure admissions: insights from real-world patient prescriptions. Acta Cardiol. 2019;74:115–22.

    PubMed  Google Scholar 

  33. De Vecchis R, Ariano C, Di Biase G, Noutsias M. In: HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization: a retrospective cohort study. Herz. 2019;44:651–8.

    PubMed  Google Scholar 

  34. De Vecchis R, Ariano C, Di Biase G, Noutsias M. Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction: a retrospective cohort study. Herz. 2019;44:425–32.

    PubMed  Google Scholar 

  35. Vardeny O, Claggett B, Kachadourian J, et al. Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial. Eur J Heart Fail. 2019;21:337–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Cacciatore F, Amarelli C, Maiello C, et al. Sacubitril/valsartan in patients listed for heart transplantation: effect on physical frailty. ESC Heart Fail. 2020;7(2):757–762.

  37. Romano G, Vitale G, Ajello L, et al. The effects of sacubitril/valsartan on clinical, biochemical and echocardiographic parameters in patients with heart failure with reduced ejection fraction: the “hemodynamic recovery”. J Clin Med. 2019;8:2165.

    CAS  PubMed Central  Google Scholar 

  38. Pugliese NR, Fabiani I, Zywicki V, et al. Effects of sacubitril/valsartan on B-type natriuretic peptide circulating levels and loop diuretic dose in a case series of stabilized heart failure patients with left ventricular ejection fraction ≤35. Curr Med Res Opin. 2019;35(sup3):13–8.

    CAS  PubMed  Google Scholar 

  39. Solomon SD, McMurray JJV, Anand IS, et al. PARAGON-HF Investigators and Committees. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381:1609–20.

    CAS  PubMed  Google Scholar 

  40. Wachter R, Senni M, Belohlavek J, et al. TRANSITION Investigators. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail. 2019;21:998–1007.

    CAS  PubMed  Google Scholar 

  41. Velazquez EJ, Morrow DA, DeVore AD, et al. PIONEER-HF Investigators. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380:539–48.

    CAS  PubMed  Google Scholar 

  42. DeVore AD, Braunwald E, Morrow DA, et al. PIONEER-HF Investigators. Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: secondary analysis of the open-label extension of the PIONEER-HF Trial. JAMA Cardiol. 2019;5:202–7.

    Google Scholar 

  43. Senni M, Wachter R, Witte KK, et al. TRANSITION Investigators. Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. Eur J Heart Fail. 2020;22:303–12.

    CAS  PubMed  Google Scholar 

  44. Solomon SD, Vaduganathan M, Claggett BL, et al. Sacubitril/valsartan across the spectrum of ejection fraction in heart failure. Circulation. 2020;141:352–61.

    PubMed  Google Scholar 

  45. McMurray JJV, Jackson AM, Lam CSP, et al. Effects of Sacubitril-valsartan versus valsartan in women compared with men with heart failure and preserved ejection fraction: insights from PARAGON-HF. Circulation. 2020;141:338–51.

    PubMed  Google Scholar 

  46. Vaduganathan M, Claggett BL, Desai AS, et al. Prior heart failure hospitalization, clinical outcomes, and response to sacubitril/valsartan compared with valsartan in HFpEF. J Am Coll Cardiol. 2020;75:245–54.

    CAS  PubMed  Google Scholar 

  47. Selvaraj S, Claggett B, Pozzi A, et al. Prognostic implications of congestion on physical examination among contemporary patients with heart failure and reduced ejection fraction: PARADIGM-HF. Circulation. 2019;140:1369–79.

    CAS  PubMed  Google Scholar 

  48. Desai AS, Solomon SD, Shah AM, et al. EVALUATE-HF Investigators. Effect of sacubitril-valsartan vs enalapril on aortic stiffness in patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2019;322:1–10.

    Google Scholar 

  49. Balmforth C, Simpson J, Shen L, et al. Outcomes and effect of treatment according to etiology in HFrEF: an analysis of PARADIGM-HF. JACC Heart Fail. 2019;7:457–65.

    PubMed  Google Scholar 

  50. Morrow DA, Velazquez EJ, DeVore AD, et al. Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF Trial. Circulation. 2019;139:2285–8.

    PubMed  Google Scholar 

  51. Sumarsono A, Vaduganathan M, Ajufo E, et al. Contemporary patterns of Medicare and Medicaid utilization and associated spending on sacubitril/valsartan and ivabradine in heart failure. JAMA Cardiol. 2019;5:336–9.

    Google Scholar 

  52. Perera K, Ademi Z, Liew D, Zomer E. Sacubitril-valsartan versus enalapril for acute decompensated heart failure: a cost-effectiveness analysis. Eur J Prev Cardiol. 2019;2047487319878953. https://doi.org/10.1177/2047487319878953.

  53. van der Pol S, de Jong LA, Vemer P, Jansen DEMC, Postma MJ. Cost-effectiveness of sacubitril/valsartan in Germany: an application of the efficiency frontier. Value Health. 2019;22:1119–27.

    PubMed  Google Scholar 

  54. Borges M, Afonso-Silva M, Laires PA, et al. Cost-effectiveness of sacubitril/valsartan for the treatment of patients with heart failure with reduced ejection fraction in Portugal. Expert Rev Pharmacoecon Outcomes Res. 2020;20:199–205.

    PubMed  Google Scholar 

  55. Park SK, Hong SH, Kim H, Kim S, Lee EK. Cost-utility analysis of sacubitril/valsartan use compared with standard care in chronic heart failure patients with reduced ejection fraction in South Korea. Clin Ther. 2019;41:1066–79.

    PubMed  Google Scholar 

  56. Albert NM, Swindle JP, Buysman EK, Chang C. Lower hospitalization and healthcare costs with sacubitril/valsartan versus angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker in a retrospective analysis of patients with heart failure. J Am Heart Assoc. 2019;8:e011089.

    PubMed  PubMed Central  Google Scholar 

  57. Correale M, Monaco I, Ferraretti A, et al. Hospitalization cost reduction with sacubitril-valsartan implementation in a cohort of patients from the Daunia Heart Failure Registry. Int J Cardiol Heart Vasc. 2019;22:102–4.

    PubMed  PubMed Central  Google Scholar 

  58. Selvaraj S, Claggett BL, Böhm M, et al. Systolic blood pressure in heart failure with preserved ejection fraction treated with sacubitril/valsartan. J Am Coll Cardiol. 2020;75:1644–56.

    CAS  PubMed  Google Scholar 

  59. Huo Y, Li W, Webb R, Zhao L, Wang Q, Guo W. Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: a randomized, double-blind, 8-week study. J Clin Hypertens (Greenwich). 2019;21:67–76.

    CAS  Google Scholar 

  60. Li Q, Li L, Wang F, et al. Effect and safety of LCZ696 in the treatment of hypertension: a meta-analysis of 9 RCT studies. Medicine (Baltimore). 2019;98:e16093.

    CAS  Google Scholar 

  61. De Vecchis R, Ariano C, Soreca S. Antihypertensive effect of sacubitril/valsartan: a meta-analysis. Minerva Cardioangiol. 2019;67:214–22.

    PubMed  Google Scholar 

  62. De Vecchis R, Soreca S, Ariano C. Anti-hypertensive effect of sacubitril/valsartan: a meta-analysis of randomized controlled trials. Cardiol Res. 2019;10:24–33.

    PubMed  PubMed Central  Google Scholar 

  63. Correale M, Mallardi A, Mazzeo P, et al. Sacubitril/valsartan improves right ventricular function in a real-life population of patients with chronic heart failure: the Daunia Heart Failure Registry. Int J Cardiol Heart Vasc. 2020;27:100486.

    PubMed  PubMed Central  Google Scholar 

  64. Moliner-Abós C, Rivas-Lasarte M, Pamies Besora J, et al. Sacubitril/valsartan in real-life practice: experience in patients with advanced heart failure and systematic review. Cardiovasc Drugs Ther. 2019;33:307–14.

    PubMed  Google Scholar 

  65. Lee S, Oh J, Kim H, et al. Sacubitril/valsartan in patients with heart failure with reduced ejection fraction with end-stage of renal disease. ESC Heart Fail. 2020;7(3):1125–1129.

  66. Quiroga B, de Santos A, Sapiencia D, Saharaui Y, Álvarez-Chiva V. Sacubitril/valsartan in chronic kidney disease, the nephrologist point of view. Nefrologia. 2019;39:646–52.

    PubMed  Google Scholar 

  67. Chang HY, Feng AN, Fong MC, et al. Sacubitril/valsartan in heart failure with reduced ejection fraction patients: real world experience on advanced chronic kidney disease, hypotension, and dose escalation. J Cardiol. 2019;74:372–80.

    PubMed  Google Scholar 

  68. Martín-Garcia A, López-Fernández T, Mitroi C, et al. Effectiveness of sacubitril-valsartan in cancer patients with heart failure. ESC Heart Fail. 2020;7(2):763–767.

  69. Martín-García A, Díaz-Peláez E, Martín-García AC, Sánchez-González J, Ibáñez B, Sánchez PL. Myocardial function and structure improvement with sacubitril/valsartan in cancer therapy-induced cardiomyopathy. Rev Esp Cardiol (Engl Ed). 2020;73:268–9.

    Google Scholar 

  70. Sheppard CE, Anwar M. The use of sacubitril/valsartan in anthracycline-induced cardiomyopathy: a mini case series. J Oncol Pharm Pract. 2019;25:1231–4.

    CAS  PubMed  Google Scholar 

  71. Maurer SJ, Pujol Salvador C, Schiele S, Hager A, Ewert P, Tutarel O. Sacubitril/valsartan for heart failure in adults with complex congenital heart disease. Int J Cardiol. 2020;300:137–40.

    PubMed  Google Scholar 

  72. Lluri G, Lin J, Reardon L, Miner P, Whalen K, Aboulhosn J. Early experience with sacubitril/valsartan in adult patients with congenital heart disease. World J Pediatr Congenit Heart Surg. 2019;10:292–5.

    PubMed  Google Scholar 

  73. Appadurai V, Thoreau J, Malpas T, Nicolae M. Sacubitril/valsartan in adult congenital heart disease patients with chronic heart failure—a single centre case series and call for an international registry. Heart Lung Circ. 2020;29:137–41.

    PubMed  Google Scholar 

  74. Kang DH, Park SJ, Shin SH, et al. Angiotensin receptor neprilysin inhibitor for functional mitral regurgitation. Circulation. 2019;139:1354–65.

    CAS  PubMed  Google Scholar 

  75. El-Battrawy I, Pilsinger C, Liebe V, et al. Impact of sacubitril/valsartan on the long-term incidence of ventricular arrhythmias in chronic heart failure patients. J Clin Med. 2019;8:1582.

    CAS  PubMed Central  Google Scholar 

  76. Vicent L, Méndez-Zurita F, Viñolas X, et al. Clinical characteristics of patients with sustained ventricular arrhythmias after sacubitril/valsartan initiation. Heart Vessel. 2020;35:136–42.

    Google Scholar 

  77. Vicent L, Juárez M, Bruña V, et al. Clinical profile and ventricular arrhythmias after sacubitril/valsartan initiation. Cardiology. 2019;142:26–7.

    PubMed  Google Scholar 

  78. Martens P, Nuyens D, Rivero-Ayerza M, et al. Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction. Clin Res Cardiol. 2019;108:1074–82.

    CAS  PubMed  Google Scholar 

  79. Giblin EM, Adams KF Jr, Hill L, et al. Comparison of hydralazine/nitrate and angiotensin receptor neprilysin inhibitor use among black versus nonblack Americans with heart failure and reduced ejection fraction (from CHAMP-HF). Am J Cardiol. 2019;124:1900–6.

    CAS  PubMed  Google Scholar 

  80. Vicent L, Ayesta A, Esteban-Fernández A, et al. Sex influence on the efficacy and safety of sacubitril/valsartan. Cardiology. 2019;142:73–8.

    PubMed  Google Scholar 

  81. De Vecchis R, Paccone A, Di Maio M. Favorable effects of sacubitril/valsartan on the peak atrial longitudinal strain in patients with chronic heart failure and a history of one or more episodes of atrial fibrillation: a retrospective cohort study. J Clin Med Res. 2020;12:100–7.

    PubMed  PubMed Central  Google Scholar 

  82. Valentim Gonçalves A, Galrinho A, Pereira-da-Silva T, et al. Myocardial work improvement after sacubitril-valsartan therapy: a new echocardiographic parameter for a new treatment. J Cardiovasc Med (Hagerstown). 2020;21:223–30.

    Google Scholar 

  83. Díez-Villanueva P, Vicent L, de la Cuerda F, et al. Left ventricular ejection fraction recovery in patients with heart failure and reduced ejection fraction treated with sacubitril/valsartan. Cardiology. 2020;15:1–8.

    Google Scholar 

  84. Nakou ES, Marketou ME, Patrianakos A, Protonotarios A, Vardas PE, Parthenakis FI. Short-term effects of angiotensin receptor-neprilysin inhibitors on diastolic strain and tissue Doppler parameters in heart failure patients with reduced ejection fraction: a pilot trial. Hellenic J Cardiol. 2019;S1109-9666(19):30308–2.

    Google Scholar 

  85. Suo Y, Yuan M, Li H, et al. Sacubitril/valsartan improves left atrial and left atrial appendage function in patients with atrial fibrillation and in pressure overload-induced mice. Front Pharmacol. 2019;10:1285.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. De Vecchis R, Paccone A, Di Maio M. Sacubitril/valsartan therapy for 14 months induces a marked improvement of global longitudinal strain in patients with chronic heart failure: a retrospective cohort study. Cardiol Res. 2019;10:293–302.

    PubMed  PubMed Central  Google Scholar 

  87. De Vecchis R, Paccone A, Di Maio M. Sacubitril/valsartan improves left ventricular longitudinal deformation in heart failure patients with reduced ejection fraction. Minerva Cardioangiol. 2019;67:456–63.

    PubMed  Google Scholar 

  88. Karagodin I, Kalantari S, Yu DB, et al. Echocardiographic evaluation of the effects of sacubitril-valsartan on vascular properties in heart failure patients. Int J Cardiovasc Imaging. 2020;36:271–8.

    PubMed  Google Scholar 

  89. Chang HY, Chen KC, Fong MC, et al. Recovery of left ventricular dysfunction after sacubitril/valsartan: predictors and management. J Cardiol. 2019;S0914-5087(19):30264–3.

    Google Scholar 

  90. Bayard G, Da Costa A, Pierrard R, Roméyer-Bouchard C, Guichard JB, Isaaz K. Impact of sacubitril/valsartan on echo parameters in heart failure patients with reduced ejection fraction a prospective evaluation. Int J Cardiol Heart Vasc. 2019;25:100418.

    PubMed  PubMed Central  Google Scholar 

  91. De Vecchis R, Paccone A, Di Maio M. In heart failure with reduced ejection fraction patients' left ventricular global longitudinal strain is enhanced after 1-year therapy with sacubitril/valsartan compared with conventional therapy with angiotensin-converting enzyme-inhibitors or AT1 blockers: results from a retrospective cohort study. J Cardiovasc Med (Hagerstown). 2019;20:857–8.

    Google Scholar 

  92. Wang Y, Zhou R, Lu C, Chen Q, Xu T, Li D. Effects of the Angiotensin-receptor neprilysin inhibitor on cardiac reverse remodeling: meta-analysis. J Am Heart Assoc. 2019;8(13):e012272.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Santangelo G, Bursi F, Toriello F, et al. Sacubitril/valsartan improves medium-term reverse left ventricular remodeling: why wait? J Cardiovasc Med (Hagerstown). 2019;20:727–9.

    Google Scholar 

  94. Cosentino ER, Degli Esposti D, Miceli R, et al. Sacubitril/valsartan improves both functional and echocardiographic parameters in patients with chronic heart failure with reduced ejection fraction. Curr Med Res Opin. 2019;35(sup1):9–12.

    CAS  PubMed  Google Scholar 

  95. Acanfora D, Scicchitano P, Acanfora C, et al. Early initiation of sacubitril/valsartan in patients with chronic heart failure after acute decompensation: a case series analysis. Clin Drug Investig. 2020;40(5):493–501.

  96. Malfatto G, Ravaro S, Caravita S, et al. Improvement of functional capacity in sacubitril-valsartan treated patients assessed by cardiopulmonary exercise test. Acta Cardiol. 2019;2:1–5.

    Google Scholar 

  97. Morillas-Climent H, Seller-Moya J, Vicedo-López Á, et al. Evolution of functional class, biochemical and echocardiographic parameters and clinical outcomes after sacubitril/valsartan initiation in daily practice. J Comp Eff Res. 2019;8:685–97.

    PubMed  Google Scholar 

  98. Vitale G, Romano G, Di Franco A, et al. Early effects of sacubitril/valsartan on exercise tolerance in patients with heart failure with reduced ejection fraction. J Clin Med. 2019;8:262.

    CAS  PubMed Central  Google Scholar 

  99. Lau CW, Martens P, Lambeets S, Dupont M, Mullens W. Effects of sacubitril/valsartan on functional status and exercise capacity in real-world patients. Acta Cardiol. 2019;74:405–12.

    PubMed  Google Scholar 

  100. Palau P, Mollar A, Domínguez E, Sanchis J, Bayés-Genís A, Núñez J. Early sacubitril/valsartan-driven benefit on exercise capacity in heart failure with reduced ejection fraction: a pilot study. Rev Esp Cardiol (Engl Ed). 2019;72:167–9.

    Google Scholar 

  101. Dereli S, Kılınçel O, Çerik İB, Kaya A. Impact of sacubitril/valsartan treatment on depression and anxiety in heart failure with reduced ejection fraction. Acta Cardiol. 2020;18:1–9.

    Google Scholar 

  102. Holmlund L, Brännström M, Lindmark K, Sandberg C, Hellström ÄK. Health-related quality of life in patients with heart failure eligible for treatment with sacubitril-valsartan. Nurs Open. 2019;7:556–62.

    PubMed  PubMed Central  Google Scholar 

  103. Khariton Y, Fonarow GC, Arnold SV, et al. Association between sacubitril/valsartan initiation and health status outcomes in heart failure with reduced ejection fraction. JACC Heart Fail. 2019;7(11):933–41.

    PubMed  PubMed Central  Google Scholar 

  104. Chandra A, Vaduganathan M, Lewis EF, et al. PARAGON-HF Investigators. Health-related quality of life in heart failure with preserved ejection fraction: The PARAGON-HF Trial. JACC Heart Fail. 2019;7:862–74.

    PubMed  Google Scholar 

  105. De Vecchis R, Ariano C, Di Biase G, Noutsias M. Cognitive performance of patients with chronic heart failure on sacubitril/valsartan: a retrospective cohort study. Herz. 2019;44:534–40.

    PubMed  Google Scholar 

  106. Okutucu S, Fatihoglu SG, Sabanoglu C, et al. Effects of angiotensin receptor neprilysin inhibition on P-wave dispersion in heart failure with reduced ejection fraction. Herz. 2019. https://doi.org/10.1007/s00059-019-04872-4.

  107. Marchitto N, Sindona F, Mobilia P, Dalmaso SG, Raimondi G. Effect of low-dose sacubitril/valsartan on body composition, bioelectrical impedance analysis, heart rate variability and T-peak to T-end index in elderly patients with severe chronic heart failure: a pilot experience. Curr Med Res Opin. 2019;35(sup1):13–5.

    CAS  PubMed  Google Scholar 

  108. Pastor-Pérez FJ, García-Alberola A, Navarro-Peñalver M, et al. Lack of improvement in autonomic cardiac tone after sacubitril/valsartan at lower than target doses. J Electrocardiol. 2019;52:99–100.

    PubMed  Google Scholar 

  109. Okutucu S, Sabanoglu C, Yetis Sayin B, Aksoy H, Bursa N, Oto A. Switching from ramipril to sacubitril/valsartan favorably alters electrocardiographic indices of ventricular repolarization in heart failure with reduced ejection fraction. Acta Cardiol. 2020;75:20–5.

    PubMed  Google Scholar 

  110. Januzzi JL Jr, Prescott MF, Butler J, et al. PROVE-HF Investigators. Association of change in N-terminal pro-B-type Nvatriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction. JAMA. 2019;322:1–11.

    Google Scholar 

  111. Abellas-Sequeiros M, Del Prado DS, Del Rey JM, Alonso-Salinas GL, Zamorano JL. Sacubitril/valsartan and B-type natriuretic peptide value: recalculating route. Eur J Heart Fail. 2020;22:162–3.

    PubMed  Google Scholar 

  112. Morrow DA, Velazquez EJ, DeVore AD, et al. Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial. Eur Heart J. 2019;40:3345–52.

    PubMed  PubMed Central  Google Scholar 

  113. Ibrahim NE, McCarthy CP, Shrestha S, et al. Effect of neprilysin inhibition on various natriuretic Peptide Assays. J Am Coll Cardiol. 2019;73:1273–84.

    CAS  PubMed  Google Scholar 

  114. Myhre PL, Vaduganathan M, Claggett B, et al. B-type natriuretic peptide during treatment with Sscubitril/valsartan: The PARADIGM-HF Trial. J Am Coll Cardiol. 2019;73:1264–72.

    CAS  PubMed  Google Scholar 

  115. Zile MR, O’Meara E, Claggett B, et al. Effects of sacubitril/valsartan on biomarkers of extracellular matrix regulation in patients with HFrEF. J Am Coll Cardiol. 2019;73:795–806.

    CAS  PubMed  Google Scholar 

  116. Nougué H, Pezel T, Picard F, et al. Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study. Eur J Heart Fail. 2019;21(5):598–605.

  117. Chalikias G, Kikas P, Thomaidis A, et al. Effect of sacubitril/valsartan on circulating catecholamine levels during a 6-month follow-up in heart failure patients. Timeo Danaos et dona ferentes? Acta Cardiologica.

  118. Pereira NL, Desai VK, Jaffe AS. Beneficial effects of sacubitril/valsartan in heart failure with reduced ejection fraction: pas à cause du BNP? Eur J Heart Fail. 2019;21:609–12.

    PubMed  PubMed Central  Google Scholar 

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Chalikias, G., Tziakas, D. Angiotensin Receptor Neprilysin Inhibitors—2019 Update. Cardiovasc Drugs Ther 34, 707–722 (2020). https://doi.org/10.1007/s10557-020-07015-8

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