N Engl J Med

ACC 2025: Investigational drug lowers BP in uncontrolled hypertension

April 28, 2025

Lorundrostat reduced BP in patients with uncontrolled hypertension, with a manageable safety profile, suggesting that the aldosterone synthase inhibitor could be a valuable addition to the therapeutic options for patients with resistant hypertension. Trial results were shared at the recent American College of Cardiology’s 2025 Scientific Session.

Study details: In the phase 2b Advance-HTN study, 285 participants with uncontrolled hypertension (defined as a BP of ≥140/90 mm Hg despite taking 2-5 antihypertensive medications) were randomized to receive either placebo, lorundrostat at a stable dose of 50 mg daily, or lorundrostat with dose adjustment from 50 - 100 mg daily based on BP response. Primary endpoint was change in 24-hour average systolic BP from start to week 12, comparing the results with a placebo in each lorundrostat group.

Results:

After 12 weeks, the change in 24-hour average systolic BP was as follows:

• Stable-dose group: -15.4 mm Hg (97.5% confidence interval [CI] -19.0 to -11.8)
• Dose-adjustment group: -13.9 mm Hg (97.5% CI -17.6 to -10.3)
• Placebo group: -7.4 mm Hg (97.5% CI -11.4 to -3.4)

The placebo-adjusted change in BP was -7.9 mm Hg (97.5% CI, -13.3 to -2.6) in the stable-dose group and -6.5 mm Hg (97.5% CI, -11.8 to -1.2) in the dose-adjustment group. Notably, 5% of participants in the stable-dose group and 7% in the dose-adjustment group experienced elevated potassium levels >6.0 mmol/L, which resolved with dose adjustment or discontinuation.

Source:

Laffin LJ, et al; Advance-HTN Investigators. (2025, April 23). N Engl J Med. Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension. https://pubmed.ncbi.nlm.nih.gov/40267417/