Background: Daily doses of spironolactone higher than 25 mg are rarely used in heart failure (HF) patients, presumably due to the concern for hyperkalemia. However, in advanced HF, doses ≥50 mg have been found to be necessary to produce natriuresis. The aim of the present study was to examine the safety of natriuretic doses of spironolactone (50–200 mg) on serum potassium concentration in New York Heart Association (NYHA) class III/IV HF patients over several weeks. Methods: 18 patients with advanced HF received 50–200 mg of spironolactone in addition to standard treatment. Serum electrolytes, BUN and serum creatinine were assessed at baseline, during increased doses of spironolactone and at the 1-month follow-up. Results: During a total of 738 patient-weeks, there was no significant increase in mean serum potassium (4.0 vs. 4.2 mEq/l) or serum creatinine (1.3 vs. 1.4 mg/dl). However, in 3 patients, spironolactone treatment was stopped due to a mean increase in serum creatinine (1.9 vs. 2.6 mg/dl) and in one of them, an increase in serum potassium (4.4 vs. 5.2 mEq/l) was noted. Conclusion: Increased doses of spironolactone are generally safe during outpatient follow-up in selected patients with advanced HF, who are receiving treatment with ACE inhibitors, beta-blockers, and loop diuretics.

Keywords:
Spironolactone, Hyperkalemia, Heart failure
1.
Pitt B, Zannad F, Remme WJ, et al; Randomized Aldactone Evaluation Study Investigators: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709–717.
2.
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309–1321.
3.
Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B; EMPHASIS-HF Study Group: Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11–21.
4.
The RALES Investigators: Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (The Randomized Aldactone Evaluation Study [RALES]). Am J Cardiol 1996;78:902–907.
5.
Testani JM, Chen J, McCauley BD, Kimmel SE, Shannon RP: Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival. Circulation 2010;122:265–272.
6.
Juurlink D, Mamdani M, Lee DS, et al: Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004;351:543–551.
7.
Li W, Struthers AD, Fahey T, Watson AD, MacDonald TM: Spironolactone use and renal toxicity: population based longitudinal analysis. BMJ 2010;340:c1768.
8.
Schrier RW: Aldosterone ‘escape’ versus ‘breakthrough’. Nat Rev Nephrol 2010;6:61.
9.
Jencks SF, Williams MV, Coleman EA: Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med 2009;360:1418–1428.
10.
Schrier RW: Decreased effective blood volume in edematous disorders: what does this mean? J Am Soc Nephrol 2007;18:2028–2031.
11.
Bansal S, Lindenfeld JA, Schrier RW: Sodium retention in heart failure and cirrhosis: potential role of natriuretic doses of mineralocorticoid antagonist? Circ Heart Fail 2009;2:370–376.
12.
Ginès P, Schrier RW: Renal failure in cirrhosis. N Engl J Med 2009;361:1279–1290.
13.
Braunwald E, Plauth HW Jr, Morrow AG: A method for the detection and quantification of impaired sodium excretion. Circulation 1965;32:223–231.
14.
Hensen J, Abraham WT, Dürr JA, Schrier RW: Aldosterone in congestive heart failure: analysis of determinants and role in sodium retention. Am J Nephrol 1991;11:441–446.
15.
Van Vliet AA, Donker AJ, Nauta JJ, et al: 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.
© 2013 S. Karger AG, Basel
2013
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