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Mineralocorticoid-receptor blockade, hypertension and heart failure

Nature Clinical Practice Endocrinology & Metabolism volume 1, pages 4–5 (2005)Cite this article

Should mineralocorticoid-receptor (MR) antagonists be used in hypertension and heart failure? In the beginning, the answer is yes. As outlined below, the mechanisms involved are still unclear, and the present focus on aldosterone rather than MRs largely misplaced. But the data are in and the message is clear, from laboratory studies and clinical trials, in particular RALES,1 EPHESUS2 and the 4E trial.3

RALES1 was ground-breaking in a number of ways. First, spironolactone was long out of patent; this was an expensive, essentially pro bono, proof-of-principle study on progressive heart failure. Second, the trial was stopped just over halfway through, reflecting the progressive divergence in outcomes between control and treatment groups. Third, the extent of this divergence was impressive: 36 months of treatment with spironolactone plus diuretics, angiotensin-converting-enzyme inhibitors, and so on produced a 30% reduction in mortality and a 35% lower incidence of hospitalization in spironolactone-treated patients, compared with those on standard care plus placebo.

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References

  1. Pitt B et al. (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 341: 709–717

    Article  CAS  Google Scholar 

  2. Pitt B et al. (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348: 1309–1321

    Article  CAS  Google Scholar 

  3. Pitt B et al. (2003) Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 108: 1831–1838

    Article  CAS  Google Scholar 

  4. Rocha R et al. (2002) Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat heart. Endocrinology 143: 4828–4836

    Article  CAS  Google Scholar 

  5. Juurlink D et al. (2004) Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 351: 543–551

    Article  CAS  Google Scholar 

  6. Bozkurt B et al. (2003) Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am Coll Cardiol 41: 211–214

    Article  CAS  Google Scholar 

  7. Levy D et al. (2004) Distinguishing the antihypertensive and electrolyte effects of eplerenone. J Clin Endocrinol Metab 89: 2736–2740

    Article  CAS  Google Scholar 

  8. Funder JW et al. (1988) Mineralocorticoid action: target-tissue specificity is enzyme, not receptor, mediated. Science 242: 583–585

    Article  CAS  Google Scholar 

  9. Funder JW and Myles K (1996) Exclusion of corticosterone from epithelial mineralocorticoid receptors is insufficient for selectivity of aldosterone action: in vivo binding studies. Endocrinology 137: 5264–5268

    Article  CAS  Google Scholar 

  10. Funder JW (2004) Is aldosterone bad for the heart? Trends Endocrinol Metab 15: 139–142

    Article  CAS  Google Scholar 

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  1. Professor of Medicine at Monash University, a Senior Fellow at Prince Henry's Institute, Monash Medical Centre, Melbourne, and a Professorial Associate of the Centre for Neuroscience, University of Melbourne, Australia

    John W Funder

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  1. John W Funder
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Correspondence to John W Funder.

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Competing interests

Dr Funder is a consultant for Eli Lilly, Merck, Pfizer, cBio, Exelisis, GNF and Kalypsis, and holds research grants from Merck and Pfizer.

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Funder, J. Mineralocorticoid-receptor blockade, hypertension and heart failure. Nat Rev Endocrinol 1, 4–5 (2005). https://doi.org/10.1038/ncpendmet0016

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