Beyond Mineralocorticoid Receptor Blockade: Aldosterone Synthase Inhibition as a New Therapeutic Frontier in the Cardiovascular–Kidney–Metabolic Era-What is really new?

Abstract

Aldosterone dysregulation links persistent hypertension with sodium retention, inflammation, fibrosis, and cardiovascular–kidney–metabolic (CKM) injury. This narrative review examines traditional mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) alongside selective aldosterone synthase inhibitors (ASIs) targeting CYP11B2. Focused literature searches and trial-registry review through November 5, 2026 informed a critical synthesis of pharmacology, phase 2 and phase 3 antihypertensive trials, chronic kidney disease studies, safety, and clinical positioning. Randomized trials show additional blood-pressure lowering with baxdrostat and lorundrostat, while the negative primary endpoint of HALO cautions against unqualified extrapolation. Early studies suggest reductions in albuminuria when ASIs are used with guideline-directed kidney therapy, including sodium–glucose cotransporter-2 inhibitors, but durable cardiorenal outcome benefits and comparative superiority over mineralocorticoid receptor antagonists remain unproven. Suspected primary aldosteronism requires appropriate biochemical evaluation before starting agents that may alter aldosterone and renin measurements. In Mexico, the substantial burden of uncontrolled hypertension underscores the need for validated patient selection, electrolyte monitoring, equitable access, and implementation research. Selective CYP11B2 inhibition expands therapeutic options in uncontrolled and resistant hypertension without displacing established receptor-antagonist indications or proven CKM care.