Abstract 113: Aldosterone Synthase Inhibition With Lorundrostat For The Treatment Of Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial

Importance: Excess aldosterone production contributes to hypertension in both classical hyperaldosteronism and obesity-associated hypertension. Objective: To compare the safety and efficacy of lorundrostat, an aldosterone synthase inhibitor, with placebo, and characterize dose-dependent safety and efficacy. Design, Setting, and Participants: Randomized, placebo-controlled, dose-ranging, double-blind clinical trial among adults with uncontrolled hypertension taking 2 or more antihypertensive medications. A first cohort of participants with suppressed plasma renin (plasma renin activity (PRA) of less than 1.0 ng/mL/h) and elevated plasma aldosterone (greater than 1.0 ng/dL) were enrolled (n=163), with subsequent enrollment of participants with PRA greater than 1.0 ng/mL/h (n=37). Interventions: Participants were randomized to placebo or one of five doses of lorundrostat (12.5, 50, or 100 mg once daily, or 12.5 or 25 mg twice daily.) Results: Following 8 weeks of treatment in participants with suppressed PRA, dose-dependent changes in office systolic BP were observed (figure). The primary endpoint, placebo-subtracted change in modeled systolic BP was -9.6 mmHg (90% confidence interval [CI], -15.8 to -3.4, p=0.01) for the 50 mg once daily dose and -7.8 mmHg (90% CI, -14.1 to -1.5, p=0.04) for 100 mg daily. Six participants had increases in serum potassium above 6.0 mmol/L that were reversed with dose reduction or drug discontinuation. Conclusions and Relevance: Among individuals with uncontrolled hypertension, use of lorundrostat was effective at lowering blood pressure compared with placebo.