Aldosterone antagonism: new ideas, new drugs

In the last few years our ideas about the physiological and pathological roles of aldosterone have changed enormously. It is now widely recognised that this hormone not only plays a crucial role in normal salt and water regulation, and its abnormalities in congestive heart failure and some types of hypertension, but also has other effects. These may include the promotion of cardiac and vascular inflammation and fibrosis and increased likelihood of arrhythmias. These perspectives coincide with a revived interest in aldosterone antagonists, particularly since the RALES trial showing the benefits of spironolactone in patients with congestive heart failure. This long-established drug does unfortunately have serious adverse effects, notably gynaecomastia and menstrual abnormalities. New drugs, such as eplerenone, are being developed which are more selective for the aldosterone receptor and have less interaction with receptors for other steroid hormones. Early studies indicate that this drug may have comparable efficacy to spironolactone in patients with hypertension and heart failure, while adverse effects appear to be less frequent and severe. The development of such compounds will encourage greater emphasis on aldosterone antagonism in cardiovascular drug therapy.