Cardiology Letters 2025, 34(5):261-269

Aldosterone synthase inhibitors in the treatment of arterial hypertension

Juraj Dúbrava

Oddelenie neinvazívnej kardiológie, Univerzitná nemocnica Bratislava, Slovenská republika

Aldosterone plays a key role in blood pressure regulation. Aldosterone dysregulation occurs in approximately 30% of hypertensive patients. Mineralocorticoid receptor antagonists (MRA) are currently the only class of antihypertensive drugs that specifically target aldosterone. However, MRAs are underused due to concerns about adverse effects; they do not block the nongenomic effect of aldosterone, and are associated with a reactive increase in aldosterone levels. A promising option to MRA are aldosterone synthase inhibitors (ASI), which change the concept of antialdosterone effect. They act "one step ahead" of MRA. ASI inhibit aldosterone synthesis, while MRA antagonize aldosterone receptor binding. ASI have the potential to overcome several problems associated with MRA. Two highly selective ASI (CYP11B2) are in advanced clinical research for the indication of arterial hypertension - lorundrostat and baxdrostat. Due to their high selectivity, they do not interfere with 11β-hydroxylase (CYP11B1), and therefore there is no risk of hypocortisolism.The results of phase 2 and 3 studies for lorundrostat (Advance-HTN, Target-HTN, and Launch-HTN) and for baxdrostat (BrigHTN and BaxHTN) are comparable. In patients with uncontrolled or resistant hypertension, the addition of lorundrostat or baxdrostat to background therapy significantly reduces blood pressure. The safety profile of both substances was satisfactory and comparable to other drug groups aimed at suppressing the renin-angiotensin-aldosterone system.

Keywords: aldosterone synthase inhibitors; lorundrostat; baxdrostat; arterial hypertension; aldosterone

Published: May 1, 2025  Show citation