Hyperkalemia in congestive heart failure patients aged 63 to 85 years with subclinical renal disease

Abstract

Prolonged treatment with an angiotensin-converting enzyme (ACE) inhibitor does not permanently suppress aldosterone production. Increased aldosterone production often resumes after a variable interval. The failure to suppress aldosterone production permanently is termed “aldosterone escape.” 1 Borghi C. Boschi S. Ambrosioni E. Melandri G. Branzi A. Magnani B. Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors. J Clin Pharmacol. 1993; 33: 40-45 Crossref PubMed Scopus (132) Google Scholar , 2 Struthers A.D. Aldosterone escape during angiotensin converting enzyme inhibitor therapy in chronic heart failure. J Card Fail. 1996; 2: 47-54 Abstract Full Text PDF PubMed Scopus (220) Google Scholar The addition of spironolactone to ACE inhibitor therapy in patients with refractory congestive heart failure has been advocated because of this escape phenomenon. 3 van Vilet A. Donker A.J.M. Nauta J.J.P. Verhengt F.W.A. Spironolactone in congestive heart failure refractory to high dose loop diuretic and low dose angiotensin-converting enzyme inhibitor. Am J Cardiol. 1993; 71: 21A-28A Abstract Full Text PDF PubMed Scopus (145) Google Scholar However, it was not until the landmark Randomized Aldactone Evaluation Study (RALES) by Pitt et al 4 Pitt B. Zannad F. Remme W.J. Cody R. Castaigne A. Perez A. Palensky J. Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999; 341: 709-717 Crossref PubMed Scopus (7416) Google Scholar that widespread use of this combination therapy became uniformly practiced by cardiologists and general internists. The incidence of dangerous hyperkalemia was 2% and insignificant in the RALES study, 4 Pitt B. Zannad F. Remme W.J. Cody R. Castaigne A. Perez A. Palensky J. Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999; 341: 709-717 Crossref PubMed Scopus (7416) Google Scholar but patients with insulin-dependent diabetes mellitus and those with serum creatinine ≥2.0 mg/dl (≥176.8 μmol/L) were excluded. There are increasing reports of hyperkalemic complications in elderly patients with pre-existing renal disease after exposure to this combination of drugs. 5 Berry C, McMurray JJ. Serious adverse events experienced by patients with chronic heart failure taking spironolactone. Heart 2001;85:E8 Google Scholar , 6 Vanpee D, Swine CH. Elderly heart failure patients with drug-induced serious hyperkalemia. Aging (Milano) 2000;12:315–319 Google Scholar , 7 Schepkens H. Vanholder R. Billiouw J. Lameire N. Life-threatening hyperkelemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone an analysis of 25 cases. Am J Med. 2001; 110: 438-441 Abstract Full Text Full Text PDF PubMed Scopus (239) Google Scholar Because serum creatinine may be normal in elderly patients who may already have moderate to severe reduction of their glomerular filtration rate and they also have altered electrolyte homeostasis, elderly patients are therefore at risk for hyperkalemia and other electrolyte derangements. 8 Beck L.H. The aging kidney. Defending a delicate balance of fluid and electrolytes. Geriatrics. 2000; 55 (31–32): 26-28 PubMed Google Scholar Underappreciation of the presence of a reduced glomerular filtration rate in the elderly potentially places them at great risk for hyperkalemia and acute renal failure when exposed to this combination therapy. In this report, we present 18 patients (aged 63 to 85 years) whose serum creatinine levels were apparently normal but who had significantly reduced glomerular filtration rates. They developed hyperkalemia after exposure to combination therapy with spironolactone and ACE inhibitors.