Aldosterone antagonists clinical trials

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

Antihypertensive drug name and dose is associated with compelling indications which are based on benefits from outcome studies or clinical guidelines. For example, the drug class aldosterone antagonists have eplerenone dosed at 25-50 mg per day which is indicated for heart failure patients after an Ml and supported by the EPHESUS trial. 

Based on clinical trial results demonstrating reduced mortality, low-dose aldosterone antagonists may be appropriate for (1) patients with moderately severe to severe HF who are receiving standard therapy and (2) those with LV dysfunction early after MI. 

Overall, clinical trials have impressively demonstrated that aldosterone is a major contributor to cardiovascular morbidity and mortality in patients with arterial hypertension and heart failure. However, the currently available MR antagonists suffer from two substantial drawbacks that limit their benefit in clinical practice, i.e. lack of selectivity (in the case of spironolactone) and limited efficacy (in the case of eplerenone). Consequently a second race for new aldosterone antagonists has started, in search of a compound which ideally should combine the potency and efficacy of spironolactone with the selectivity of eplerenone. 

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