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Aldosterone antagonists in the treatment and prevention of heart failure

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Aldosterone is elevated in heart failure and exerts multiple detrimental effects. In addition to playing key roles in sodium and volume regulation, aldosterone is involved in regulation of autonomic tone, endothelial dysfunction, tissue collagen turnover, myocyte fibrosis, and release of inflammatory modulators. Aldosterone receptor antagonists have proven to be a valuable treatment tool in the management of heart failure due to systolic dysfunction. Blocking the effects of aldosterone can improve many of the functions that are deranged in patients with heart failure, as well as promote excretion of sodium and water and preservation of potassium and hydrogen in the distal renal tubule. These medications can be especially effective at removing fluid from the periphery and soft tissues. Prevention of hypokalemia, which may predispose patients to arrhythmia, is an added benefit. Spironolactone and eplerenone are the two agents in this class that have been studied in patients with heart failure and left ventricular dysfunction. However, aldosterone antagonist therapy may not be appropriate for all patients with heart failure. Therefore, guidelines in managing patients on these medications should be followed to avoid serious electrolyte abnormalities and renal dysfunction. This review examines some of the mechanisms of action and the usefulness of aldosterone blockade in the management of heart failure.

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References and Recommended Reading

  1. Weber KT: Aldosterone in congestive heart failure. N Engl J Med 2001, 345:1689–1697.

    Article  PubMed  CAS  Google Scholar 

  2. McKelvie RS, Yusuf S, Pericak D, et al.: Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999, 100:1056–1064.

    PubMed  CAS  Google Scholar 

  3. Struthers AD: Aldosterone blockade in cardiovascular disease. Heart 2004, 90:1229–1234. The most recent and concise review of aldosterone and aldosterone antagonism in heart failure.

    Article  PubMed  Google Scholar 

  4. Rajagopalan S, Pitt B: Aldosterone as a target in congestive heart failure. Med Clin North Am 2003, 87:441–457.

    Article  PubMed  CAS  Google Scholar 

  5. Francis J, Weiss RM, Wei SG, et al.: Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure. Am J Physiol Heart Circ Physiol 2001, 281:H2241-H2251.

    PubMed  CAS  Google Scholar 

  6. Francis J, Beltz T, Johnson AK, Felder RB: Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-alpha in normal rats. Am J Physiol Regul Integr Comp Physiol 2003, 285:R1402-R1409.

    PubMed  CAS  Google Scholar 

  7. Farquharson CA, Struthers AD: Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/ angiotensin II conversion in patients with chronic heart failure. Circulation 2000, 101:594–597.

    PubMed  CAS  Google Scholar 

  8. Gonzalez A, Lopez B, Diez J: Fibrosis in hypertensive heart disease: role of the renin-angiotensin-aldosterone system. Med Clin North Am 2004, 88:83–97.

    Article  PubMed  CAS  Google Scholar 

  9. Kuster GM, Kotlyar E, Rude MK, et al.: Mineralocorticoid receptor inhibition ameliorates the transition to myocardial failure and decreases oxidative stress and inflammation in mice with chronic pressure overload. Circulation 2005, 111:420–427.

    Article  PubMed  CAS  Google Scholar 

  10. Katada J, Meguro T, Saito H, et al.: Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor-knockout mice after myocardial infarction. Circulation 2005, 111:2157–2164.

    Article  PubMed  CAS  Google Scholar 

  11. Zannad F, Alla F, Dousset B, et al.: Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation 2000, 102:2700–2706.

    PubMed  CAS  Google Scholar 

  12. 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, 341:709–717.

    Article  PubMed  CAS  Google Scholar 

  13. Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321. This trial gave further evidence and added that patients in the period after myocardial infarction with resultant heart failure benefit from selective aldosterone antagonism.

    Article  PubMed  CAS  Google Scholar 

  14. Juurlink DN, Mamdani MM, Lee DS, et al.: Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004, 351:543–551. This paper discusses the use of spironolactone after publication of the RALES trial. An excellent example of “real world” application of evidence-based medicine and the resultant effects.

    Article  PubMed  CAS  Google Scholar 

  15. Tamirisa KP, Aaronson KD, Koelling TM: Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. Am Heart J 2001, 148:971–978.

    Article  Google Scholar 

  16. Bozkurt B, Agoston I, Knowlton AA: Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am Coll Cardiol 2003, 41:211–214.

    Article  PubMed  CAS  Google Scholar 

  17. Palmer BF: Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med 2004, 351:585–592.

    Article  PubMed  CAS  Google Scholar 

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Boxer, R.S., Dunlap, M.E. Aldosterone antagonists in the treatment and prevention of heart failure. Curr Treat Options Cardio Med 7, 431–436 (2005). https://doi.org/10.1007/s11936-005-0027-x

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  • DOI: https://doi.org/10.1007/s11936-005-0027-x

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