Aldosterone synthase inhibition for the treatment of hypertension and the derived mechanistic requirements for a new therapeutic strategy.

Context: We describe the clinical investigation of the first generation aldosterone synthase inhibitor, LCI699, in patients with essential, uncontrolled, resistant, or secondary hypertension. LCI699 competitively reduced blood pressure at lower doses yet counterintuitive effects were observed at higher doses.

Objective And Method: An extensive endocrine biomarker analysis was performed to better understand the pharmacological mechanism of the drug.