Baxdrostat: A Next-Generation Aldosterone Synthase Inhibitor Offering New Hope in Resistant Hypertension

Abstract

Hypertension is a leading global cause of cardiovascular disease and mortality, with resistant hypertension (RH) posing treatment challenges. Aldosterone synthase inhibitors (ASIs) are a novel drug class that reduce blood pressure by lowering aldosterone levels. Baxdrostat is a selective ASI that inhibits the CYP11B2 enzyme, responsible for aldosterone synthesis, without affecting cortisol production. This selectivity minimizes hormonal side effects. Clinical trials have shown that baxdrostat reduces plasma aldosterone in a dose-dependent manner while preserving cortisol levels. In the Phase 2 BrigHTN trial, baxdrostat significantly lowered systolic and diastolic blood pressure in patients with RH, with the 2 mg dose showing the most consistent efficacy. However, in the HALO trial, similar blood pressure reductions were observed in the placebo group, possibly due to improved adherence to background antihypertensive therapy. Baxdrostat has demonstrated a favorable safety profile, with mostly mild adverse effects and no significant impact on kidney function. It is considered safe for use with other medications, including metformin. Ongoing trials are investigating its potential in patients with chronic kidney disease (CKD) and primary hyperaldosteronism (PA). Baxdrostat represents a promising therapeutic option for aldosterone-driven hypertension, especially in patients unresponsive to standard treatments.