Baxdrostat for the treatment of primary aldosteronism: current evidence.

Primary aldosteronism (PA) is a common form of secondary hypertension, estimated to affect up to 20% of individuals with resistant hypertension. High levels of aldosterone induce several genomic and nongenomic effects, which lead to comorbidities beyond high blood pressure (BP), including excess cardiovascular and renal risk. Adrenalectomy is the treatment of choice for unilateral PA, while mineralocorticoid receptor antagonists (MRAs) represent the standard medical treatment for PA. However, many individuals fail to achieve complete medical treatment responses. This may be partly due to treatment‑limiting adverse effects and to the inability of MRAs to target mineralocorticoid receptor–independent pathways. As a result, the nongenomic actions of aldosterone – which may remain elevated – are not fully blocked, and its detrimental effects may persist. Selective aldosterone synthase (CYP11B2) inhibition has recently emerged as an alternative strategy for treating uncontrolled and resistant hypertension. Through highly selective CYP11B2 inhibition, baxdrostat was reported to significantly lower systolic and diastolic BP, while reducing aldosterone levels, with relatively low rates of hyperkalemia or serious adverse events, in phase II and III trials (BrigHTN, FigHTN, BaxHTN). Similarly, in patients with confirmed PA, a phase II trial (SPARK-PA) reported significant BP reductions, with aldosterone-to-renin ratio improvements indicative of complete biochemical response. Several phase III trials are currently studying the potential of baxdrostat not only in PA (BaxPA), but also its impact on cardiovascular and renal outcomes (BaxDuo Arctic, BaxDuo Pacific, Prevent-HF). Baxdrostat might become an important therapeutic option for PA, particularly for patients who are not candidates for adrenalectomy, who decline it, or do not have complete response with MRAs. If long-term studies confirm benefits on cardiovascular and renal outcomes, baxdrostat could redefine the medical management of PA and potentially serve as an equally effective alternative to adrenalectomy in selected patients.