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Current Cardiology Reviews

Editor-in-Chief

ISSN (Print): 1573-403X
ISSN (Online): 1875-6557

Review Article

Recently Approved and Under Investigation Drugs for Treating Patients with Heart Failure

Author(s): Yaniel Castro-Torres* and Richard E. Katholi

Volume 16, Issue 3, 2020

Page: [202 - 211] Pages: 10

DOI: 10.2174/1573403X14666180702151626

Price: $65

Abstract

Heart Failure (HF) represents a leading cause of morbidity and mortality worldwide. Despite the recent advances in the treatment of this condition, patients´ prognosis remains unfavorable in most cases. Sacubitril/valsartan and ivabradine have been recently approved to improve clinical outcomes in patients with HF with reduced ejection fraction. Drugs under investigation for treating patients with HF encompass many novel mechanisms including vasoactive peptides, blocking inflammatory- mediators, natriuretic peptides, selective non-steroidal mineralocorticoid-receptor antagonists, myocardial β3 adrenoreceptor agonists, inhibiting the cytochrome C/cardiolipin peroxidase complex, neuregulin-1/ErbB signaling and inhibiting late inward sodium current. The aim of this manuscript is to review the main drugs under investigation for the treatment of patients with HF and give perspectives for their implementation into clinical practice.

Keywords: Heart failure, heart failure reduced ejection fraction, heart failure preserved ejection fraction, heart failure treatment, heart failure management, drugs for HF.

Graphical Abstract
[1]
McKelvie RS, Moe GW, Ezekowitz JA, et al. The 2012 Canadian Cardiovascular Society heart failure management guidelines update: Focus on acute and chronic heart failure. Can J Cardiol 2013; 29(2): 168-81.
[http://dx.doi.org/10.1016/j.cjca.2012.10.007] [PMID: 23201056]
[2]
Rossignol P, Hernandez AF, Solomon SD, Zannad F. Heart failure drug treatment. Lancet 2019; 393(10175): 1034-44.
[http://dx.doi.org/10.1016/S0140-6736(18)31808-7] [PMID: 30860029]
[3]
Benjamin EJ, Muntner P, Alonso A, et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2019 update: A report from the american heart association. Circulation 2019; 139(10): e56-e528.
[http://dx.doi.org/10.1161/CIR.0000000000000659] [PMID: 30700139]
[4]
Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136(6): e137-61.
[http://dx.doi.org/10.1161/CIR.0000000000000509] [PMID: 28455343]
[5]
Ponikowski P, Voors AA, Anker SD, et al. ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37(27): 2129-200.
[http://dx.doi.org/10.1093/eurheartj/ehw128] [PMID: 27206819]
[6]
Heidenreich PA, Albert NM, Allen LA, et al. American Heart Association Advocacy Coordinating Committee. Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Stroke Council. Forecasting the impact of heart failure in the United States: A policy statement from the American Heart Association. Circ Heart Fail 2013; 6(3): 606-19.
[http://dx.doi.org/10.1161/HHF.0b013e318291329a] [PMID: 23616602]
[7]
Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. 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(5): 293-302.
[http://dx.doi.org/10.1056/NEJM199108013250501] [PMID: 2057034]
[8]
Young JB1, Dunlap ME, Pfeffer MA, et al.. Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Investigators and Committees. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: Results of the CHARM low left ventricular ejection fraction trials. Circulation 2004; 110: 2618-26.
[http://dx.doi.org/10.1161/01.CIR.0000146819.43235.A9] [PMID: 15492298]
[9]
Rademaker MT, Charles CJ, Espiner EA, Nicholls MG, Richards AM, Kosoglou T. Neutral endopeptidase inhibition: Augmented atrial and brain natriuretic peptide, haemodynamic and natriuretic responses in ovine heart failure. Clin Sci (Lond) 1996; 91(3): 283-91.
[http://dx.doi.org/10.1042/cs0910283] [PMID: 8869410]
[10]
McMurray JJ, Packer M, Desai AS, et al. PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition vs. enalapril in heart failure. N Engl J Med 2014; 371(11): 993-1004.
[http://dx.doi.org/10.1056/NEJMoa1409077] [PMID: 25176015]
[11]
Solomon SD, Claggett B, Desai AS, et al. Influence of ejection fraction on outcomes and efficacy of sacubitril/valsartan (LCZ696) in heart failure with reduced ejection fraction: The prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure (PARADIGM-HF) trial. Circ Heart Fail 2016; 9(3) e002744
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002744] [PMID: 26915374]
[12]
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(6): 457-65.
[http://dx.doi.org/10.1016/j.jchf.2019.02.015] [PMID: 31078482]
[13]
Packer M, Claggett B, Lefkowitz MP, et al. Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: A secondary analysis of the PARADIGM-HF trial. Lancet Diabetes Endocrinol 2018; 6(7): 547-54.
[http://dx.doi.org/10.1016/S2213-8587(18)30100-1] [PMID: 29661699]
[14]
Ahn R, Prasad V. Do limitations in the design of PARADIGM-HF justify the slow real world uptake of sacubitril/valsartan (Entresto)? Cardiovasc Drugs Ther 2018; 32(6): 633-5.
[http://dx.doi.org/10.1007/s10557-018-6830-x] [PMID: 30232657]
[15]
Chen CH. Critical questions about PARADIGM-HF and the future. Acta Cardiol Sin 2016; 32(4): 387-96.
[PMID: 27471351]
[16]
Velazquez EJ, Morrow DA, DeVore AD, et al. PIONEER-HF Investigators. PIONEER-HF Investigators. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med 2019; 380(6): 539-48.
[http://dx.doi.org/10.1056/NEJMoa1812851] [PMID: 30415601]
[17]
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(8): 998-1007.
[http://dx.doi.org/10.1002/ejhf.1498] [PMID: 31134724]
[18]
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(6): 1066-79.
[http://dx.doi.org/10.1016/j.clinthera.2019.04.031] [PMID: 31101372]
[19]
Valentim Gonçalves A, Pereira-da-Silva T, Galrinho A, et al. Antiarrhythmic effect of sacubitril-valsartan: Cause or consequence of clinical improvement? J Clin Med 2019; 8(6) E869
[http://dx.doi.org/10.3390/jcm8060869] [PMID: 31216679]
[20]
Aimo A, Emdin M, Maisel AS. Sacubitril/Valsartan, cardiac fibrosis, and remodeling in heart failure. J Am Coll Cardiol 2019; 73(23): 3038-9.
[http://dx.doi.org/10.1016/j.jacc.2019.03.510] [PMID: 31196469]
[21]
Badu-Boateng C, Jennings R, Hammersley D. The therapeutic role of ivabradine in heart failure. Ther Adv Chronic Dis 2018; 9(11): 199-207.
[http://dx.doi.org/10.1177/2040622318784556] [PMID: 30364460]
[22]
Sattar Y, Neisani Samani E, Zafrullah F, Latchana S, Patel NB. Ivabradine in congestive heart failure: Patient selection and perspectives. Cureus 2019; 11(4) e4448
[http://dx.doi.org/10.7759/cureus.4448] [PMID: 31205834]
[23]
Fox K, Ford I, Steg PG, Tendera M, Ferrari R. BEAUTIFUL Investigators. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): A randomised, double-blind, placebo-controlled trial. Lancet 2008; 372(9641): 807-16.
[http://dx.doi.org/10.1016/S0140-6736(08)61170-8] [PMID: 18757088]
[24]
Swedberg K, Komajda M, Böhm M, et al. SHIFT Investigators. Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: Is there an influence of beta-blocker dose?: Findings from the SHIFT (Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial) study. J Am Coll Cardiol 2012; 59(22): 1938-45.
[http://dx.doi.org/10.1016/j.jacc.2012.01.020] [PMID: 22617188]
[25]
Pei H, Miao W, Xie WZ, et al. Ivabradine improves cardiac function and increases exercise capacity in patients with chronic heart failure. Int Heart J 2019; 60(4): 899-909.
[http://dx.doi.org/10.1536/ihj.18-559] [PMID: 31308326]
[26]
Bonnet D, Berger F, Jokinen E, Kantor PF, Daubeney PEF. Ivabradine in children with dilated cardiomyopathy and symptomatic chronic heart failure. J Am Coll Cardiol 2017; 70(10): 1262-72.
[http://dx.doi.org/10.1016/j.jacc.2017.07.725] [PMID: 28859790]
[27]
Hasenfuss G, Mann DL. Pathophysiology of heart failurebraunwald’s heart disease: A textbook of cardiovascular medicine. 11th ed. Elsevier 2019; pp. 442-61.
[28]
Dalzell JR, Rocchiccioli JP, Weir RA, et al. The emerging potential of the apelin-APJ system in heart failure. J Card Fail 2015; 21(6): 489-98.
[http://dx.doi.org/10.1016/j.cardfail.2015.03.007] [PMID: 25795508]
[29]
Goidescu CM, Vida-Simiti LA. The apelin-APJ system in the evolution of heart failure. Clujul Med 2015; 88(1): 3-8.
[PMID: 26528040]
[30]
Wang M, Gupta RC, Rastogi S, et al. Effects of acute intravenous infusion of apelin on left ventricular function in dogs with advanced heart failure. J Card Fail 2013; 19(7): 509-16.
[http://dx.doi.org/10.1016/j.cardfail.2013.05.004] [PMID: 23834927]
[31]
Barnes GD, Alam S, Carter G, et al. Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure. Circ Heart Fail 2013; 6(3): 482-91.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.111.000077] [PMID: 23519586]
[32]
Van Tassell BW, Seropian IM, Toldo S, Mezzaroma E, Abbate A. Interleukin-1β induces a reversible cardiomyopathy in the mouse. Inflamm Res 2013; 62(7): 637-40.
[http://dx.doi.org/10.1007/s00011-013-0625-0] [PMID: 23649041]
[33]
Toldo S, Mezzaroma E, Bressi E, et al. Interleukin-1β blockade improves left ventricular systolic/diastolic function and restores contractility reserve in severe ischemic cardiomyopathy in the mouse. J Cardiovasc Pharmacol 2014; 64(1): 1-6.
[http://dx.doi.org/10.1097/FJC.0000000000000106] [PMID: 25006675]
[34]
Toldo S, Mezzaroma E, Van Tassell BW, et al. Interleukin-1β blockade improves cardiac remodelling after myocardial infarction without interrupting the inflammasome in the mouse. Exp Physiol 2013; 98(3): 734-45.
[http://dx.doi.org/10.1113/expphysiol.2012.069831] [PMID: 23180808]
[35]
Toldo S, Mauro AG, Cutter Z, Abbate A. Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2018; 315(6): H1553-68.
[http://dx.doi.org/10.1152/ajpheart.00158.2018] [PMID: 30168729]
[36]
Van Tassell BW, Canada J, Carbone S, et al. Interleukin-1 blockade in recently decompensated systolic heart failure: Results from the REcently Decompensated Heart failure Anakinra Response Trial (REDHART). Circ Heart Fail 2017; 10(11) e004373
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004373] [PMID: 29141858]
[37]
Van Tassell BW, Trankle CR, Canada JM, et al. IL-1 blockade in patients with heart failure with preserved ejection fraction. Results From DHART2. Circ Heart Fail 2018; 11(8) e005036
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.118.005036] [PMID: 30354558]
[38]
Meems LMG, Burnett JC Jr. Designer natriuretic peptides. JACC Basic Transl Sci 2016; 1(7): 557-67.
[http://dx.doi.org/10.1016/j.jacbts.2016.10.001] [PMID: 28497128]
[39]
Ichiki T, Dzhoyashvili N, Burnett JC Jr. Natriuretic peptide based therapeutics for heart failure: Cenderitide: A novel first-in-class designer natriuretic peptide. Int J Cardiol 2019; 281: 166-71.
[http://dx.doi.org/10.1016/j.ijcard.2018.06.002] [PMID: 29941213]
[40]
Kawakami R, Lee CYW, Scott C, et al. A human study to evaluate safety, tolerability, and cyclic GMP activating properties of a novel designer natriuretic peptide, cenderitide, in subjects with stable chronic heart failure. Clin Pharmacol Ther 2018; 104: 546-52.
[http://dx.doi.org/10.1002/cpt.974] [PMID: 29226471]
[41]
Albert NM, Yancy CW, Liang L, et al. Use of aldosterone antagonists in heart failure. JAMA 2009; 302(15): 1658-65.
[http://dx.doi.org/10.1001/jama.2009.1493] [PMID: 19843900]
[42]
Bärfacker L, Kuhl A, Hillisch A, et al. Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem 2012; 7(8): 1385-403.
[http://dx.doi.org/10.1002/cmdc.201200081] [PMID: 22791416]
[43]
Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J 2016; 37(27): 2105-14.
[http://dx.doi.org/10.1093/eurheartj/ehw132] [PMID: 27130705]
[44]
Pei H, Wang W, Zhao D, Wang L, Su GH, Zhao Z. The use of a novel non-steroidal mineralocorticoid receptor antagonist finerenone for the treatment of chronic heart failure: A systematic review and meta-analysis. Medicine (Baltimore) 2018; 97(16) e0254
[http://dx.doi.org/10.1097/MD.0000000000010254] [PMID: 29668577]
[45]
Rozec B, Gauthier C. beta3-adrenoceptors in the cardiovascular system: Putative roles in human pathologies. Pharmacol Ther 2006; 111(3): 652-73.
[http://dx.doi.org/10.1016/j.pharmthera.2005.12.002] [PMID: 16480771]
[46]
Bundgaard H, Liu CC, Garcia A, et al. β(3) adrenergic stimulation of the cardiac Na+-K+ pump by reversal of an inhibitory oxidative modification. Circulation 2010; 122(25): 2699-708.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.964619] [PMID: 21135361]
[47]
Belge C, Hammond J, Dubois-Deruy E, et al. Enhanced expression of β3-adrenoceptors in cardiac myocytes attenuates neurohormone-induced hypertrophic remodeling through nitric oxide synthase. Circulation 2014; 129(4): 451-62.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.004940] [PMID: 24190960]
[48]
Sacco E, Bientinesi R. Mirabegron: A review of recent data and its prospects in the management of overactive bladder. Ther Adv Urol 2012; 4(6): 315-24.
[http://dx.doi.org/10.1177/1756287212457114] [PMID: 23205058]
[49]
Bundgaard H, Axelsson A, Hartvig Thomsen J, et al. The first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: The BEAT-HF trial. Eur J Heart Fail 2017; 19(4): 566-75.
[http://dx.doi.org/10.1002/ejhf.714] [PMID: 27990717]
[50]
Pouleur AC, Anker S, Brito D, et al. Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH). ESC Heart Fail 2018; 5(5): 830-41.
[http://dx.doi.org/10.1002/ehf2.12306] [PMID: 29932311]
[51]
El-Hattab AW, Zarante AM, Almannai M, Scaglia F. Therapies for mitochondrial diseases and current clinical trials. Mol Genet Metab 2017; 122(3): 1-9.
[http://dx.doi.org/10.1016/j.ymgme.2017.09.009] [PMID: 28943110]
[52]
Mann DL. Targeting myocardial energetics in the failing heart: Are we there yet? Circ Heart Fail 2017; 10(12) e004658
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004658] [PMID: 29217758]
[53]
Sabbah HN, Gupta RC, Singh-Gupta V, Zhang K, Lanfear DE. Abnormalities of mitochondrial dynamics in the failing heart: Normalization following long-term therapy with elamipretide. Cardiovasc Drugs Ther 2018; 32(4): 319-28.
[http://dx.doi.org/10.1007/s10557-018-6805-y] [PMID: 29951944]
[54]
Daubert MA, Yow E, Dunn G, et al. Novel mitochondria-targeting peptide in heart failure treatment. Circ Heart Fail 2017; 10(12) e004389
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004389] [PMID: 29217757]
[55]
Lenneman CG. Neuregulin-1 signaling in the pathogenesis of chemotherapy-induced heart failure. Curr Heart Fail Rep 2014; 11(2): 134-8.
[http://dx.doi.org/10.1007/s11897-014-0193-9] [PMID: 24682830]
[56]
Gassmann M, Casagranda F, Orioli D, et al. Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor. Nature 1995; 378(6555): 390-4.
[http://dx.doi.org/10.1038/378390a0] [PMID: 7477376]
[57]
Crone SA, Zhao YY, Fan L, et al. ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 2002; 8(5): 459-65.
[http://dx.doi.org/10.1038/nm0502-459] [PMID: 11984589]
[58]
Fukazawa R, Miller TA, Kuramochi Y, et al. Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt. J Mol Cell Cardiol 2003; 35(12): 1473-9.
[http://dx.doi.org/10.1016/j.yjmcc.2003.09.012] [PMID: 14654373]
[59]
Gao R, Zhang J, Cheng L, et al. A Phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure. J Am Coll Cardiol 2010; 55(18): 1907-14.
[http://dx.doi.org/10.1016/j.jacc.2009.12.044] [PMID: 20430261]
[60]
Jabbour A, Hayward CS, Keogh AM, et al. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail 2011; 13(1): 83-92.
[http://dx.doi.org/10.1093/eurjhf/hfq152] [PMID: 20810473]
[61]
Task Force Members Montalescot G, Sechtem U, et al. . ESC guidelines on the management of stable coronary artery disease: The task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34: 2949-3003.
[62]
Fihn SD, Gardin JM, Abrams J, et al. American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American College of Physicians; American Association for Thoracic Surgery; Preventive Cardiovascular Nurses Association; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012; 60(24): e44-e164.
[http://dx.doi.org/10.1016/j.jacc.2012.07.013] [PMID: 23182125]
[63]
Mezincescu A, Karthikeyan VJ, Nadar SK. Ranolazine: A true pluripotent cardiovascular drug or jack of all trades, master of none? Sultan Qaboos Univ Med J 2018; 18(1): e13-23.
[http://dx.doi.org/10.18295/squmj.2018.18.01.003] [PMID: 29666676]
[64]
Doshi D, Morrow JP. Potential application of late sodium current blockade in the treatment of heart failure and atrial fibrillation. Rev Cardiovasc Med 2009; 10(1): S46-52.
[PMID: 19898288]
[65]
Riccio G, Antonucci S, Coppola C, et al. Ranolazine attenuates trastuzumab-induced heart dysfunction by modulating ROS production. Front Physiol 2018; 9: 38.
[http://dx.doi.org/10.3389/fphys.2018.00038] [PMID: 29467663]
[66]
Maier LS, Layug B, Karwatowska-Prokopczuk E, et al. RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: The RALI-DHF proof-of-concept study. JACC Heart Fail 2013; 1(2): 115-22.
[http://dx.doi.org/10.1016/j.jchf.2012.12.002] [PMID: 24621836]
[67]
Murray GL, Colombo J. Ranolazine preserves and improves left ventricular ejection fraction and autonomic measures when added to guideline-driven therapy in chronic heart failure. Heart Int 2014; 9(2): 66-73.
[http://dx.doi.org/10.5301/heartint.5000219] [PMID: 27004101]

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