Aldosterone Synthase Inhibitors in Resistant Hypertension
Guido Damianich, MD1*, Noelia Roldán, MD2
1Cardiologist specialising in hypertension; Director, Hypertension Unit, and Attending Physician, Cardiometabolic Diseases Unit, Canning Health Institute, Canning, Buenos Aires, Argentina; Former Director and current Advisor, Hypertension Council, Argentine Society of Cardiology.
2Cardiologist specialising in hypertension; Attending Physician, Hypertension Unit and Echocardiography Department, Canning Health Institute, Canning, Buenos Aires, Argentina.
*Corresponding Author: Guido Damianich, Director, Hypertension Unit, and Attending Physician, Cardiometabolic Diseases Unit, Canning Health Institute, Canning, Buenos Aires, Argentina; Former Director and current Advisor, Hypertension Council, Argentine Society of Cardiology.
https://doi.org/10.58624/SVOAMR.2026.04.001
Received: December 26, 2025
Published: January 09, 2026
Citation: Damianich G, Roldán N. Aldosterone Synthase Inhibitors in Resistant Hypertension. SVOA Medical Research 2026, 4:1, 01-10. doi: 10.58624/ SVOAMR.2026.04.001
Abstract
Resistant hypertension is a high-risk clinical phenotype characterised by persistent blood pressure elevation despite optimised combination therapy and is associated with an increased burden of cardiovascular and renal complications. Aldosterone excess and dysregulated sodium handling play a central role in the pathophysiology of treatment resistance. Current international guidelines recommend mineralocorticoid receptor antagonists as fourth-line therapy, supported by robust clinical evidence. However, their use is limited by adverse effects, incomplete blood pressure control in a substantial proportion of patients, and persistent aldosterone exposure, prompting interest in alternative therapeutic strategies. Highly selective, novel aldosterone synthase inhibitors have recently demonstrated consistent blood pressure–lowering effects in patients with uncontrolled and resistant hypertension, without clinically relevant interference with cortisol synthesis. Emerging phase II and III data support their potential role as a novel and complementary treatment option, offering a more mechanism-based and individualised approach to the management of resistant hypertension.
Keywords: Resistant hypertension, Aldosterone, Mineralocorticoid receptor antagonists, Aldosterone synthase inhibitors, Renin–angiotensin–aldosterone system, Cardio–renal–metabolic syndrome