Spironolactone and heart failure

HOUSTON, TEXAS. Researchers at the Veterans Affairs Medical Center at Baylor College of Medicine have just completed a study aimed at determining the extent of complications resulting from the use of the potassium-sparing diuretic, spironolactone, in the treatment of heart failure patients. The use of spironolactone took a big jump after the release of the results of the RALES trial in July 1999. The RALES trial involved heart failure patients with class III or class IV disease and a left ventricular ejection fraction (LVEF) of less than 0.35 – in other words, pretty sick people. The trial found that the addition of 12.5 to 25 mg/day of spironolactone to the conventional treatment with beta-blockers and ACE inhibitors decreased mortality by about 30%.

The authors of the RALES study set out quite specific guidelines for the use of spironolactone and the Baylor College researchers wanted to see how well these guidelines were being followed in actual practice. Their study involved 104 patients who had been put on spironolactone following the publication of the RALES trial. Their findings revealed a serious mismatch between the RALES guidelines and their application in actual practice.

Only 25% of the 104 patients met the inclusion criteria from RALES (class III or IV heart failure) with most having less severe disease than experienced among the RALES patients.
All patients in the RALES study had a LVEF of less than 35%. Only 55% of the 104 patients had a LVEF of less than 35%.
The average daily dose of spironolactone used was 41 mg/day versus 26 mg/day in RALES.
31% had renal insufficiency at the start of spironolactone use. Patients with renal insufficiency were excluded from the RALES trial.
The average daily dose of ACE inhibitors was twice as high among the 104 patients as compared to the RALES dosage.
40% of the 104 patients were continued on potassium supplements even though they had no signs of hypokalemia.

Thus, even though the 104 patients had less advanced disease than the RALES patients they were far heavier medicated. This, combined with poor follow-up by attending physicians, led to the following complications among the 104 patients:

24% developed hyperkalemia (potassium overload) as compared to only 2% in the RALES trial.
31% developed hyponatremia (sodium deficiency).
25% developed renal insufficiency, 7% developed hypotension, and 3% needed a temporary pacemaker implant due to arrhythmias caused by severe hyperkalemia.

The researchers conclude that the rate of complications arising from the use of spironolactone in heart failure patients is significantly higher in actual practice than in a rigidly controlled clinical trial.
Bozkurt, Biykem, et al. Complications of inappropriate use of spironolactone in heart failure: When an old medicine spirals out of new guidelines. Journal of the American College of Cardiology, Vol. 41, January 15, 2003, pp. 211-14
Tang, W.H. Wilson and Francis, Gary S. Spironolactone in chronic heart failure: All's well that ends well. Journal of the American College of Cardiology, Vol. 41, January 15, 2003, pp. 215-16 (editorial comment)