Aldosterone Synthesis Inhibitors in Resistant Hypertension: The BaxHTN Trial

Abstract Inhibitors of the renin–angiotensin–aldosterone system (RAAS) remain foundational therapies for arterial hypertension across major international guidelines. Their effectiveness, however, may be partially attenuated by the phenomenon of aldosterone escape, characterized by chronic elevation of adrenal aldosterone due to activation of alternative enzymatic pathways. Mineralocorticoid receptor antagonists (MRAs) are recommended as first-line therapy for resistant hypertension, yet their clinical utility is limited by poor adherence and high discontinuation rates, driven largely by hyperkalemia and sex hormone–related adverse effects such as gynecomastia, impotence, and menstrual irregularities. Recent pharmacologic research has focused on alternative strategies for suppressing aldosterone activity, particularly through the development of selective aldosterone synthase inhibitors (ASI). This approach has led to the emergence of highly selective agents such as baxdrostat and lorundrostat. Clinical studies have demonstrated meaningful reductions in blood pressure among patients with resistant or uncontrolled hypertension, with favorable tolerability and without clinically significant adverse events. Further studies are required to determine the impact of ASIs on hypertensive-mediated organ damage, major cardiovascular events, nephrovascular outcomes, and long-term safety.