Background: Treatment with spironolactone (SPL) is beneficial in patients with severe congestive heart failure (CHF). In the Randomized Aldactone Evaluation Study SPL was well tolerated, particularly with regard to renal function and serum K(+) levels. Our aim was to investigate whether the reported low frequency of adverse effects during SPL treatment in a heart failure study population could be confirmed in an unselected heart failure outpatient cohort and to identify potential predictors of harmful effects.
Methods and results: We investigated 125 consecutive patients with CHF recruited from our heart failure clinic. Inclusion criteria were LVEF (left ventricular ejection fraction) </=45% and treatment with SPL. Blood tests were performed bimonthly or more frequently if necessary. Outcomes measures were (1) increases in serum K(+) to >5,0, 5.5, 6.0, or 6.5 mmol/L, respectively, and (2) rise in serum creatinine to 120%, 150%, and 200% of baseline, respectively. Mean age was 72.9 years (range 46.5 to 90.6 years); 27% were women. The New York Heart Association class distribution was: I, 6%; II, 44%; III, 46%; and IV, 4%. Mean LVEF was 29+/-5%. Other medication included angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in 86% and beta-blockers in 39%. At baseline, serum creatinine levels were 117.6+/-6.5 (mean+/-standard deviation; micromol/L, normal <130) and serum K(+) was 4.2+/-0.3 mmol/L. The mean follow-up period was 11 months, and the cumulative observation period was 73 SPL treatment years. Mean peak serum-creatinine was 167.6 micromol/L+/-11.9 (45% increase from baseline) and mean peak serum K(+) was 5.0+/-0.4 mmol/L (21% increase from baseline). Sixty patients were already on SPL when admitted to the CHF clinic. The remainder were initiated on SPL. During the follow-up period 36% of the patients developed hyperkalemia (>5 mmol/L), with 10% having serum K(+) >6 mmol/L. An increase in serum creatinine of >20% was seen in 55%, and in 24% an increase of >50% was found. These alterations in serum creatinine and serum K(+) were not significantly more frequent in patients treated with angiotensin-converting enzyme inhibitors or beta-blockers or different doses of SPL.
Conclusion: SPL adverse effects (impaired renal function, increase in serum K(+)) are much more prevalent in our elderly CHF patient population than previously reported. The recommendations from our study are that (1) particular caution is mandated in elderly patients with an LVEF <20%, (2) potassium supplementation should be discontinued, (3) changes in body weight should raise concern, and (4) a dose-adjustment of the concomitant conventional diuretic regime should be considered. Care should be given to the frequent monitoring of electrolytes and renal parameters.