Aldosterone breakthrough during angiotensin-converting enzyme inhibitor therapy

The effectiveness of angiotensin-converting enzyme (ACE) inhibitors in the treatment of cardiac diseases after infarction and heart failure, and of renal disease such as diabetic nephropathy, has been reported from recent large-scale clinical trials on ACE inhibitors. However, effects of ACE inhibitors during long-term therapy have not always been optimal. In recent years, aldosterone breakthrough has been suggested as a factor potentially involved, in that aldosterone levels may not remain suppressed when an ACE inhibitor is given for a relatively long time, with circulating aldosterone concentrations perhaps increasing above pretreatment levels. To improve our understanding of aldosterone-induced organ damage, which has attracted much attention in recent years, we summarize the data on aldosterone breakthrough during ACE inhibitor treatment in various diseases, and then we consider the mechanism and clinical significance of aldosterone breakthrough. Given the wide range of indications for ACE inhibitors, further studies should be designed to examine in which diseases and for which types of patients aldosterone blockade will be indicated. At present, the mechanisms of aldosterone breakthrough remain obscure, requiring further studies, including those on regional nonepithelial effects of aldosterone.