BACKGROUND Mineralocorticoid receptor antagonists reduce morbidity and mortality in patients with heart failure but can cause hyperkalemia, which contributes to reduced use of these drugs. Hypokalemia also leads to worse outcomes in patients with heart failure and may be attenuated by mineralocorticoid receptor antagonists. METHODS AND RESULTS We assessed incidence and predictors of hyperkale...

AIMS There are currently limited data about whether the effect of spironolactone in patients with resistant arterial hypertension depends on baseline blood pressure and the presence of a secondary cause of hypertension. METHODS Patients with office systolic blood pressure (BP) >140 mmHg or diastolic BP >90 mmHg, despite treatment with at least 3 antihypertensive drugs including a diuretic, we...

BACKGROUND The RALES study showed that spironolactone, added to conventional therapy for chronic heart failure, dramatically reduced mortality. We tested the hypothesis that this benefit was partially due to improvement in endothelial function and/or to amplified suppression of the vascular renin-angiotensin axis. METHODS AND RESULTS We performed a randomized, placebo-controlled, double-blind...

AIMS To compare the absorption and clinical effect of spironolactone from an inclusion complex with beta-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease. METHODS Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples we...

Mineralocorticoid receptor (MR) activation stimulates systemic vascular and left ventricular remodeling. We hypothesized that MR contributes to pulmonary vascular and right ventricular (RV) remodeling of pulmonary hypertension (PH). We evaluated the efficacy of MR antagonism by spironolactone in two experimental PH models; mouse chronic hypoxia-induced PH (prevention model) and rat monocrotalin...

Increased aldosterone levels with consequent or diuretic-potentiated electrolyte abnormalities are an important consideration when patients with cirrhosis and ascites undergo diuresis. A simple clinical method using the urinary Na/K ratio as a guide to spironolactone dosage is outlined. Patients with a ratio greater than 1 responded well to 100 mg. of spironolactone a day; those when it was one...

BACKGROUND Concerns have been raised about the appropriateness of spironolactone use in some patients with heart failure. We studied the adoption of spironolactone therapy after publication of the Randomized Aldactone Evaluation Study (RALES) in national cohorts of older patients hospitalized for heart failure. METHODS AND RESULTS This is a study of serial cross-sectional samples of Medicare ...

BACKGROUND Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left...

Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium...