The incidence and implications of aldosterone breakthrough

Interruption of the renin-angiotensin-aldosterone system has become a leading therapeutic strategy in the treatment of chronic heart and kidney disease. Angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers do not, however, uniformly suppress the renin-angiotensin-aldosterone system. Plasma aldosterone levels are elevated in a subset of patients despite therapy. This phenomenon, known as 'aldosterone escape' or 'aldosterone breakthrough', has only been directly examined in small numbers of patients. The key questions of how often breakthrough occurs and whether breakthrough leads to worse outcomes have yet to be definitively answered. In this Review, we summarize the reported data on the incidence and clinical implications of aldosterone breakthrough, and highlight areas of uncertainty that have yet to be adequately addressed in the literature. Although the available evidence is not strong enough to support widespread screening for aldosterone breakthrough, our findings should prompt physicians to consider the phenomenon in select patients as well as guide future research efforts.