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Pharmacotherapy of congestive heart failure

Currently used and experimental drugs

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Abstract

A survey is given of the currently used therapeutics in the treatment ot chronic congestive heart failure. Symptomatic treatment is usually performed along the following lines: rest, sodium and fluid restriction to unload the decompensating heart, loop diuretics, angiotensin-converting enzyme inhibitors or other vasodilators; inotropic agenls to improve the heart's mechanical performance; attempts to counteract the neuro-endocrine compensatory mechanisms, that is the activated sympathetic nervous and renin-angiotensin aldosterone systems, as well as the rise in vasopressine levels. New insights have been obtained in the effects of cardiac glycosides, which are probably rather based on counteracting the elevated sympathetic neuronal activity than on their weak and uncertain inotropic action. Angiotensin-converling enzyme inhibitors are probably more effective than classical vasodilators owing to their additional interaction with the neuro-endocrinc compensatory mechanisms. Ibopamine, a prodrug of epinine, appears to be rather a vasodilator and antagonist of the neuro-endocrine compensatory mechanisms than an inotropic agent. The most important clinical trials addressing the efficacy and adverse reactions to the various aforementioned therapeutics are discussed. New, experimental approaches in the drug treatment of chronic congestive heart failure include Β-blockers, calcium antagonists, vasopressin antagonists and inhibitors of atrial natriuretic peptide degradation.

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References

  1. Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure.) J Am Coll Cardiol 1992;20:248–54.

    PubMed  Google Scholar 

  2. Packer M. Pathophysiology of chronic heart failure. Lancet 1992;340:88–91.

    PubMed  Google Scholar 

  3. Packer M. How should physicians view heart failure? The philosophical and physiological evolution of three conceptual models of the disease. Am J Cardiol 1993;71:3C-11C.

    PubMed  Google Scholar 

  4. van Zwieten PA, Lie Kl. Neuro-endocrine compensatory mechanisms as a target for the drug treatment of congestive heart failure. Cardiologie 1994;1:311–20.

    Google Scholar 

  5. van Zwieten PA, Lie Kl. Neuro-humorale compensatieprocessen bij chronische decompensatio cordis. De invloed van geneesmiddelen [Neuro-humoral compensation phenomena in chronic congestive heart failure. The influence of drugs]. Ned Tijdschr Geneeskd 1994;138:1208–13.

    PubMed  Google Scholar 

  6. Ritz E, Fliser D. The kidney in congestive heart failure. Eur Heart J 1991;12 suppl C:14–20.

    PubMed  Google Scholar 

  7. Packer M. Treatment of chronic heart failure. Lancet 1992; 340:92–5.

    PubMed  Google Scholar 

  8. van Zwieten PA. Neuro-endocrine effects of diuretics in heart failure. Br Heart J 1994;72:51–3.

    Google Scholar 

  9. Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, Cohn JN. Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neuro-humoral axis. Ann Intern Med 1985;103:1–6.

    PubMed  Google Scholar 

  10. Bayliss J, Norell M, Canepa-Anson R, Sutton G, Poole-Wilson P. Untreated heart failure: clinical and neuro-endocrine effects of introducing diuretics. Br Heart J 1987;57:17–22.

    PubMed  Google Scholar 

  11. Goldsmith SR, Francis G, Cohn JN. Attenuation of the pressor response to intravenous furosemide by angiotensin converting enzyme inhibition in congestive heart failure. Am J Cardiol 1989;64:1382–5.

    PubMed  Google Scholar 

  12. Ward A, Heel RC. Bumetanide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 1984;28:426–64.

    PubMed  Google Scholar 

  13. Clissold SP, Brogden RN. Piretanide. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1985;29:489–530.

    PubMed  Google Scholar 

  14. Brater DC. Clinical pharmacology of loop diuretics. Drugs 1991;41 Suppl 3:14–22.

    PubMed  Google Scholar 

  15. Di Bianco R, Shabetai R, Kossuk W, Moran J, Schlant RC, Wright R. A comparison of oral milrinone, digoxin and their combination in the treatment of patients with chronic heart failure. N Engl J Med 1989;320:677–83.

    PubMed  Google Scholar 

  16. Packer M, Gheorgiade M, Young JB, Constantini PJ, Adams KF, Cody RJ, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-convertingenzyme inhibitors. N Engl J Med 1993;329:1–7.

    PubMed  Google Scholar 

  17. Ferguson DW, Berg WJ, Sanders JS, Roach PJ, Kempf JS, Kienzle MG. Sympatho-inhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathetic neural recordings. Circulation 1989;80:65–77.

    PubMed  Google Scholar 

  18. Ferguson DW. Sympathetic mechanisms in heart failure. Patho-physiological and pharmacological implications. Circulation 1993;87 Suppl VII:VII68–75.

    Google Scholar 

  19. van Veldhuisen DJ, Manin 't Veld AJ, Dunselman PHJM, Lok DJA, Dohmen HJM, Poortermans JC, et al. Double blind, placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure. Results of the Dutch Ibopamine Multicentre Trial (DIMT). J Am Coll Cardiol 1993;22:1564–73.

    PubMed  Google Scholar 

  20. van Zwieten PA. Receptor-mediated inotropic drugs. Eur Heart J 1988;9 suppl H:85–90.

    Google Scholar 

  21. van Zwieten PA. Dopamine en dopaminerge farmaca als therapeutica bij decompensatio cordis [Dopamine and dopaminergic agents as therapeutics in congestive heart failure]. Ned Tijdschr Geneeskd 1990;47:2281–4.

    Google Scholar 

  22. Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, et al.; for the PROMISE Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468–75.

    PubMed  Google Scholar 

  23. Stevenson LW, Fonarow G. Vasodilators. A re-evaluation of their role in heart failure. Drugs 1992;43:15–6.

    Google Scholar 

  24. Cohn JN. Vasodilators in heart failure. Conclusions from VHEFT II and rationale for V-HEFT III. Drugs 1994; 47 Suppl 4:47–58.

    PubMed  Google Scholar 

  25. Francis GS, Cohn JN, Johnson G, Rector TS, Goldman S, Simon A. Plasma norepinephrine, plasma renin activity and congestive heart failure: relations to survival and the effects of therapy in V-HEFT II. Circulation 1993;87 Suppl VI:40–8.

    Google Scholar 

  26. McGrath BP, Arnolda L, Matthews PG, Jackson B, Jennings G, Kiat H, et al. Controlled trial of enalapril in congestive heart failure. Br Heart J 1985;54:405–14.

    PubMed  Google Scholar 

  27. Enalapril Congestive Heart Failure Investigators. Long-term effects of enalapril in patients with congestive heart failure: a multicenter, placebo-controlled trial. Heart Failure 1987;3: 102–7.

    Google Scholar 

  28. Riegger GAJ. The effects of ACE-inhibitors in the treatment of congestive heart failure. J Cardiovasc Pharmacol 1990; 15 Suppl 2:41–6.

    Google Scholar 

  29. SOLVD investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992;327:685–91.

    Google Scholar 

  30. Cohn JN. The prevention of heart failure — a new agenda. N Engl J Med 1992;327:725–7.

    PubMed  Google Scholar 

  31. van Zwieten PA. Inodilatoren: inotrope/vaatverwijdende farmaca met een dopaminerge component [Inodilator drugs: inotropic/vasodilator drugs with a dopaminergic component]. In: Het Medisch Jaar 1993. Houten: Bohn Stafleu van Loghum, 1993:284–92.

    Google Scholar 

  32. van Woerkens LJ, Boomsma F, Man in 't Veld AJ, Bevers MM, Verdouw PD. Differential cardiovascular and neuro-endocrine effects of epinine and dopamine in conscious pigs before and after adrenoceptor blockade. Br J Pharmacol 1992; 107:303–10.

    PubMed  Google Scholar 

  33. Bravo G, Ghysel-Burton J, Jaumin P, Godfraind T. A comparison of the inotropic effects of dopamine and epinine in human isolated cardiac preparations. J Pharmacol Exp Ther 1991;257:439–43.

    PubMed  Google Scholar 

  34. van Veldhuisen DJ. Ibopamine in heart failure. Efficacy and safety in clinical and experimental studies [dissertation]. Groningen: Rijksuniversiteit Groningen, 1993:20–9, 116–40.

    Google Scholar 

  35. van Veldhuisen DJ, Crijns Hj, Girbes ARJ, Tobé JM, Wiesfeld ACP, Lie Kl. Electro-physiologic profile of ibopamine in patients with congestive heart failure and ventricular tachycardia and relation to its effects on hemodynamics and plasma catecholamines. Am J Cardiol 1991;68:1194–202.

    PubMed  Google Scholar 

  36. Girbes ARJ, Kalisvaart CJ, van Veldhuisen DJ, Smit AJ, Pasteuning WH. Effects of ibopamine on renal haemodynamics in patients with severe congestive heart failure. Eur Heart J 1993;14:279–83.

    PubMed  Google Scholar 

  37. Dei Cas L, Metra M, Visioli O. Effects of acute and chronic ibopamine administration on resting and exercise hemodynamics, plasma catecholamines and functional capacity of patients with chronic congestive heart failure. Am J Cardiol 1992;70:629–34.

    PubMed  Google Scholar 

  38. CONSENSUS Trial Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med 1987;316: 1429–35.

    Google Scholar 

  39. 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.

    Google Scholar 

  40. Held P, Swedberg K. ACE-inhibitors in the treatment of heart failure. In: Barnett DB, editor. Congestive cardiac failure. New York: Dekker, 1993:169–83.

    Google Scholar 

  41. Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE. Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study (V-HEFT). N Engl J Med 1986;314:1547–52.

    PubMed  Google Scholar 

  42. Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of congestive heart failure. N Engl J Med 1991;325:303–10.

    PubMed  Google Scholar 

  43. Heilbrunn SM, Shali P, Bristow MR, Valentine HA, Mullin AV, Ginsberg R, et al. Increased Β-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy. Circulation 1989;79:483–90.

    PubMed  Google Scholar 

  44. Packer M. Pathophysiological mechanisms underlying the effects of Β-adrenergic agonists and antagonists on functional capacity and survival in chronic heart failure. Circulation 1990;82 Suppl 1:177–88.

    Google Scholar 

  45. Persson H, Erhardt L. Beta receptor antagonists in the treatment of heart failure. Cardiovasc Drugs Ther 1991;5:589–604.

    PubMed  Google Scholar 

  46. Bristow MR, Hershberger RE, Port JD, Gilbert EM, Sandoval A, Rasmussen R, et al. Β-Adrenergic pathways in non-failing and failing human ventricular myocardium. Circulation 1990;82 Suppl 1:112–25.

    Google Scholar 

  47. Brodde OE. Β1 and Β2-Adrenoceptors in the human heart: properties, function, and alterations in chronic heart failure. Pharmacol Rev 1991;43:203–42.

    PubMed  Google Scholar 

  48. Packer M. Role of the sympathetic nervous system in chronic heart failure. Circulation 1990;82 Suppl 1:11–6.

    Google Scholar 

  49. Anderson JL, Lutz JR, Gilbert EM, Sorenson SG, Yanowitz FG, Menlove RL, et al. A randomized trial of low-dose Β-blockade therapy for idiopathic dilated cardiomyopathy. Am J Cardiol 1985;55:471–5.

    PubMed  Google Scholar 

  50. Hjalmarson A, Waagstein F. The role of Β-blockers in the treatment of cardiomyopathy and ischaemic heart failure. Drugs 1994;47 Suppl 4:31–40.

    PubMed  Google Scholar 

  51. Reicher-Reiss H, Barasch E. Calcium antagonists in patients with heart failure. Drugs 1991;42:343–64.

    PubMed  Google Scholar 

  52. Creager MA, Faxon DP, Cutler SS, Kohlmann O, Ryan TJ, Gavras H. Contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison with the renin-angiotensin system and the sympathetic nervous system. J Am Coll Cardiol 1986;7:758–65.

    PubMed  Google Scholar 

  53. Nicod P, Waeber B, Bussien JP, Goy JJ, Turini G, Nussberger J, et al. Acute hemodynamic effect of a vascular antagonist of vasopressin in patients with congestive heart failure. Am J Cardiol 1985;55:1043–7.

    PubMed  Google Scholar 

  54. Mulinari RA, Gavras I, Wang YX, Kohlmann O, Gavras H. Effects of a vasopressin antagonist with combined antipressor and antidiuretic activities in rats with left ventricular dysfunction. Circulation 1990;81:308–11.

    PubMed  Google Scholar 

  55. Raine A, Erne P, Burgisser E. Atrial natriuretic peptide and atrial pressure in patients with congestive heart failure. N Engl J Med 1986;315:533–7.

    PubMed  Google Scholar 

  56. Eisner D, Müntze A, Kromer EP, Riegger AJ. Effectiveness of endopeptidase inhibition (candoxatril) in congestive heart failure. Am J Cardiol 1992, 70:494–8.

    PubMed  Google Scholar 

  57. Münzel T, Kurz S, Holtz J, Busse R, Steinhauer H, Just H, Drexler H. Neurohormonal inhibition and hemodynamic unloading during prolonged inhibition of ANF degradation in patients with severe chronic heart failure. Circulation 1992;86:1089–98.

    PubMed  Google Scholar 

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  1. Departments of Pharmacotherapy and Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105, AZ Amsterdam, The Netherlands

    P. A. van Zwieten

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van Zwieten, P.A. Pharmacotherapy of congestive heart failure. Pharm World Sci 16, 334–342 (1994). https://doi.org/10.1007/BF02178563

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