Emerging Therapies for Treatment-Resistant Hypertension: A Review of Lorundrostat and Related Selective Aldosterone Synthase Inhibitors

Abstract

The target-hypertension (Target-HTN) trial investigated the efficacy and safety of lorundrostat, an aldosterone synthase inhibitor, as an antihypertensive. Cohort 1 of the trial includes patients with suppressed plasma renin activity and elevated aldosterone levels. Lorundrostat doses of 100 mg and 50 mg daily significantly decreased systolic blood pressure compared to the placebo group. Cohort 2 also demonstrated a reduction in systolic blood pressure with the 100 mg daily dose of lorundrostat. Lorundrostat is more selective for the inhibition of CYP11B2 versus CYP11B1, which makes it preferable to other aldosterone synthase inhibitors that inhibit cortisol synthesis, such as osilodrostat. Phase 3 trials are needed to validate the safety and efficacy of lorundrostat, and further research should be performed on other selective aldosterone synthase inhibitors such as baxdrostat, dexfadrostat, and BI 690517.