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

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.