Aldosterone synthase inhibitors for the treatment of cardiovascular disease.

Aldosterone is essential for maintaining blood pressure during hypovolaemia and/or dehydration through genomic actions mediated by the mineralocorticoid receptor and rapid signalling pathways involving the G-protein-coupled oestrogen receptor. Inappropriate aldosterone secretion contributes to cardiovascular and renal injury in several common disorders, including resistant hypertension, primary aldosteronism and heart failure. Pharmacological blockade of the mineralocorticoid receptor has therefore become a cornerstone in the therapy of cardiovascular disease. Nevertheless, mineralocorticoid receptor antagonism does not address the pathophysiological effects that are mediated by aldosterone, and residual cardiovascular risk remains substantial in many patients. Aldosterone synthase inhibitors are a novel therapeutic strategy that have effectively lowered aldosterone concentrations and reduced blood pressure in randomized clinical trials in patients with resistant or uncontrolled hypertension and patients with chronic kidney disease. Although these findings highlight the potential therapeutic value of aldosterone synthase inhibition, data on long-term safety, effectiveness compared with mineralocorticoid receptor antagonists and effects on cardiovascular outcomes are still lacking.