Advertisement

Recently Approved Pharmacologic Agents to Improve Outcomes in Heart Failure

  • David C. BoothEmail author
  • Navin Rajagopalan
Chapter
Part of the Contemporary Cardiology book series (CONCARD)

Abstract

Traditional pharmacologic approaches to the management of patients with heart failure with reduced systolic function (HFrEF) have been based on neurohormonal inhibition on a background of hemodynamic effects. The agents that have been shown to be associated with improved outcomes in this patient population are inhibitors of the renin-angiotensin-aldosterone (RAAS) system, mineralocorticoids, and beta-blockers. More recently, two agents were FDA-approved for improved outcomes in HFrEF, sacubitril/valsartan, and ivabradine. Sacubitril/valsartan combines RAAS inhibition (valsartan) with inhibition of natriuretic peptide breakdown, while ivabradine is a novel means of heart rate control. While the evidence for clinical benefit of sacubitril/valsartan is substantial, evidence for the use of ivabradine is emerging.

Keywords

ARNI Neprilysin Ivabradine Sacubitril/valsartan HFrEF Corlanor Entresto 

References

  1. 1.
    Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. N Engl J Med. 1986;314:1547–52.CrossRefGoogle Scholar
  2. 2.
    CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl Med. 1987;316:1429–35.CrossRefGoogle Scholar
  3. 3.
    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.CrossRefGoogle Scholar
  4. 4.
    Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991;325:303–10.CrossRefGoogle Scholar
  5. 5.
    Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049–57.CrossRefGoogle Scholar
  6. 6.
    Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.CrossRefGoogle Scholar
  7. 7.
    MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet. 1999;353:2001–7.CrossRefGoogle Scholar
  8. 8.
    Pitt B, Zannad F, Remme WJ, 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.CrossRefGoogle Scholar
  9. 9.
    Kagawa CM, Sturtevant FM, Van Arman CG. Pharmacology of a new steroid that blocks salt activity of aldosterone and desoxycorticosterone. J Pharm Exp Ther. 1959;126:123–30.Google Scholar
  10. 10.
    Zannad F, McMurray JJ, Frum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.CrossRefGoogle Scholar
  11. 11.
    Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–33.CrossRefGoogle Scholar
  12. 12.
    Srikanth Y, Aronow WS, Mondal P, Chabbott DR. The evolution of natriuretic peptide augmentation in management of heart failure and the role of sacubitril/valsartan. Arch Med Sci. 2017;13:1207–16.Google Scholar
  13. 13.
    Cohn JN, Tognoni G, for the Valsartan Trial Investigators. A randomized trial of the angiotensin receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–1675.Google Scholar
  14. 14.
    O’Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365:32–43.CrossRefGoogle Scholar
  15. 15.
    Packer M, Califf RM, Konstam MA, et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation. 2002;106:920–6.CrossRefGoogle Scholar
  16. 16.
    Braunwald E. The path to an angiotensin receptor neprilysin inhibitor in the treatment of heart failure. J Am Coll Cardiol. 2015;65:1029–41.CrossRefGoogle Scholar
  17. 17.
    Ruilope LM, Dukat A, Bohm M, et al. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet. 2010;375:1255–66.CrossRefGoogle Scholar
  18. 18.
    Solomon SD, Zile M, Pieske B, 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.CrossRefGoogle Scholar
  19. 19.
    Young JB, Dunlap ME, Pfeffer MA, et al. 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.CrossRefGoogle Scholar
  20. 20.
    Chandra A, Lewis EF, Claggett BL, et al. Effects of sacubitril/valsartan on physical and social activity limitations in patients with heart failure: a secondary analysis of the PARADIGM-HF trial. JAMA Cardiol. 2018;3:498–505.  https://doi.org/10.1001/jamacardio.2018.0398 . Published online April 4.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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. 2017;2:79–85.CrossRefGoogle Scholar
  22. 22.
    Bernardez-Pereira S, Ramires FJA, de Melo RFT, Pereira-Barretto AC. Was the enalapril dose too low in the PARADIGM-HF trial? Cardiol Rev. 2018;  https://doi.org/10.1097/CRD.0000000000000193. [Epub ahead of print]
  23. 23.
    Langenickel TH, Tsubouchi C, Ayalasomayajula S, et al. The effect of LCZ696 (sacubitril/valsartan) on amyloid-ß concentrations in cerebrospinal fluid in healthy subjects. Br J Clin Pharmacol. 2016;81:878–90.CrossRefGoogle Scholar
  24. 24.
    Solomon SD, Rizkala AR, Gong 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.CrossRefGoogle Scholar
  25. 25.
    Packer M, McMurray JJ, Desai AS, et al. Angiotensin receptor neprilysin inhibition compared to enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015;131:54–61.CrossRefGoogle Scholar
  26. 26.
    Ayalasomayajula S, Langenickel T, Pal P, et al. Clinical pharmacokinetics of sacubitril/valsartan (LCZ696): a novel angiotensin receptor neprilysin inhibitor. Clin Pharmacokinet. 2017;56:1461–78.CrossRefGoogle Scholar
  27. 27.
    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:e002744.CrossRefGoogle Scholar
  28. 28.
    Sulfi S, Timmis AD. Ivabradine – the first selective sinus node I f channel inhibitor in the treatment of stable angina pectoris. Int J Clin Pract. 2006;60:222–8.CrossRefGoogle Scholar
  29. 29.
    Vilaine JP, Bidouard JP, Lesage L, et al. Anti-ischemic effects of ivabradine, a selective heart rate-reducing agent, in exercise-induced myocardial ischemia in pigs. J Cardiovasc Pharmacol. 2003;42:688–96.CrossRefGoogle Scholar
  30. 30.
    Joannides R, Moore N, Iacob M, et al. Comparative effects of ivabradine, a selective heart rate lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise. Br J Clin Pharmacol. 2006;61:127–37.CrossRefGoogle Scholar
  31. 31.
    Borer JS, Fox K, Jaillon P, et al. Antianginal and antiischemic effects of ivabradine, and I f inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation. 2003;107:817–23.CrossRefGoogle Scholar
  32. 32.
    Tendera M, Chassany O, Ferrari R, et al. Quality of life with ivabradine in patients with angina pectoris. The study assessing the morbidity and mortality benefits of the I f inhibitor ivabradine in patients with stable coronary artery disease quality of life substudy. Circ Cardiovasc Qual Outcomes. 2016;9:31–8.CrossRefGoogle Scholar
  33. 33.
    Tardif JC, Ponikowski P, Kahan T, et al. Efficacy of the I f current inhibitor ivabradine in patients with chronic stable angina receiving beta blocker therapy: a 4-month, randomize, placebo-controlled trial. Eur Heart J. 2009;30:540–8.CrossRefGoogle Scholar
  34. 34.
    European Medicines Agency. Ivabradine: European public assessment report – scientific discussion. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000597/WC500043587.pdf
  35. 35.
    Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16.CrossRefGoogle Scholar
  36. 36.
    Fox K, Ford I, Steg PG, et al. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J. 2009;30:2337–45.CrossRefGoogle Scholar
  37. 37.
    Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014;371:1091–9.CrossRefGoogle Scholar
  38. 38.
    Swedberg K, Komaida M, Bohm M, Borer JS, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled trial. Lancet. 2010;376:875–85.CrossRefGoogle Scholar
  39. 39.
    Ekman I, Chassany O, Komajda M, et al. Heart rate reduction with ivabradine and health related quality of life in patients with chronic heart failure: results from the SHIFT study. Eur Heart J. 2011;32:2395–404.CrossRefGoogle Scholar
  40. 40.
    Tardif JC, O’Meara E, Komajda M, SHIFT Investigators, et al. Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy. Eur Heart J. 2011;32:2507–15.CrossRefGoogle Scholar
  41. 41.
    Böhm M, Borer J, Ford I, et al. Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study. Clin Res Cardiol. 2013;102:11–22.CrossRefGoogle Scholar
  42. 42.
    Narayanan MA, Reddy YNV, Baskaran J, et al. Ivabradine in the treatment of systolic heart failure – a systematic review and meta-analysis. World J Cardiol. 2017;9:182–90.CrossRefGoogle Scholar
  43. 43.
    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 Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70:776–803.CrossRefGoogle Scholar
  44. 44.
    Yancy CW, Januzzi JL, Allen LA, et al. 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2018;71:201–30.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.The Gill Heart and Vascular InstituteUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.Heart Failure/Cardiac Transplant ProgramThe Gill Heart and Vascular InstituteLexingtonUSA

Personalised recommendations