Aldosterone breakthrough from a pharmacological perspective

Aldosterone (Aldo) breakthrough is a well-known phenomenon that occurs in patients with long-term renin-angiotensin aldosterone system (RAAS) blockade using inhibitors of renin or angiotensin converting enzyme or angiotensin II type 1 receptor blockers. The blockade of the mineralocorticoid receptor (MR), an Aldo binding receptor, is effective in managing patients with resistant hypertension, defined as uncontrollable blood pressure despite the concurrent use of three antihypertensive drugs. In other words, MR inhibitors are not used as first-line antihypertensive drugs in most guidelines for hypertension management. Aldo breakthrough puts hypertensive patients at higher risk of cardiovascular disease and worsens future outcomes. This review discusses Aldo secretion and the mechanism of Aldo breakthrough, dependent or independent of the RAAS, with consideration of the pharmacological aspects of this phenomenon, as well as hypothetical views.