- Question
- Does lorundrostat, an aldosterone synthase inhibitor, lower blood pressure when added to the antihypertensive regimen of adults with uncontrolled hypertension, including treatment-resistant hypertension?
- Design
- Phase 3, randomized, double-blind, placebo-controlled trial of 1083 participants at 159 sites in 13 countries, enrolled between November 2023 and September 2024. Randomization was 1:2:1 to three arms.
- Population
- Adults with uncontrolled hypertension, including treatment-resistant hypertension, taking 2 to 5 antihypertensive medications (mean age 61.6 years; 46.9% female; 63.3% with obesity).
- Intervention
- Lorundrostat 50 mg/d for 12 weeks, or lorundrostat 50 mg/d for 6 weeks followed by 100 mg/d for another 6 weeks if prespecified criteria were met (systolic BP, potassium, sodium and kidney function).
- Control
- Daily placebo for 12 weeks, added to the background antihypertensive regimen.
- Primary outcome
- Change in automated office systolic blood pressure at week 6, comparing lorundrostat 50 mg with placebo.
- Results
- In the pooled 50 mg group (n = 808), systolic BP fell by 16.9 mm Hg vs 7.9 mm Hg with placebo (least-squares mean difference -9.1 mm Hg; 95% CI, -13.3 to -4.9; P < .001).
- Safety
- Hyponatremia, hyperkalemia and reduced kidney function were reported more often with lorundrostat than with placebo. Treatment-emergent adverse events occurred in 49.9% of participants and were mostly mild or moderate; discontinuations due to these events were rare.
- Conclusion
- Lorundrostat significantly lowered blood pressure versus placebo in adults with uncontrolled hypertension, including resistant hypertension, with an acceptable safety profile.
- Why it matters
- It supports blocking aldosterone synthesis as a new pharmacologic strategy for patients who do not reach targets with available antihypertensives, although it requires monitoring of potassium, sodium and kidney function.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 18, 2026