Breaking down resistance: novel aldosterone synthase inhibitors in the management of resistant hypertension

TY - JOUR

T1 - Breaking down resistance

T2 - novel aldosterone synthase inhibitors in the management of resistant hypertension

AU - Eddison, Chai

AU - Hung, Chung

AU - Kocherry, Cyril

AU - George, Jacob

N1 - © 2025 Wolters Kluwer Health, Inc. All rights reserved

PY - 2025/8/1

Y1 - 2025/8/1

N2 - This review aims to evaluate the impact of novel aldosterone synthase inhibitors, the first new class of antihypertensives in more than 20 years, on the management of resistant hypertension. We highlight the problem of resistant hypertension in clinical practice and describe the challenging history and development of aldosterone synthase inhibitors. The review highlights clinical trial evidence to-date for all agents in this class, with a key focus on the two most mature agents baxdrostat and lorundrostat which are currently in pivotal Phase 3 trials. Both agents have demonstrated significant dose-dependent reductions in blood pressure, particularly in patients with resistant hypertension and crucially, with a minimal impact on cortisol levels. They have also shown promise with marked blood pressure reductions in patients with varying physiological profiles and few adverse events at optimised doses. However, as would be expected, both drugs are associated with increases in serum potassium levels, necessitating careful monitoring.

AB - This review aims to evaluate the impact of novel aldosterone synthase inhibitors, the first new class of antihypertensives in more than 20 years, on the management of resistant hypertension. We highlight the problem of resistant hypertension in clinical practice and describe the challenging history and development of aldosterone synthase inhibitors. The review highlights clinical trial evidence to-date for all agents in this class, with a key focus on the two most mature agents baxdrostat and lorundrostat which are currently in pivotal Phase 3 trials. Both agents have demonstrated significant dose-dependent reductions in blood pressure, particularly in patients with resistant hypertension and crucially, with a minimal impact on cortisol levels. They have also shown promise with marked blood pressure reductions in patients with varying physiological profiles and few adverse events at optimised doses. However, as would be expected, both drugs are associated with increases in serum potassium levels, necessitating careful monitoring.

KW - aldosterone synthase inhibitor

KW - Baxdrostat

KW - hypertension

KW - Lorundrostat

KW - resistant hypertension

UR - https://www.scopus.com/pages/publications/105005424671

U2 - 10.1097/HJH.0000000000004055

DO - 10.1097/HJH.0000000000004055

M3 - Review article

C2 - 40366087

SN - 0263-6352

VL - 43

SP - 1286

EP - 1295

JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 8

M1 - 10.1097/HJH.0000000000004055

ER -