Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension.
Summary
In a multicenter double-blind RCT (n=285), lorundrostat lowered 24-hour ambulatory systolic BP by 6.5–7.9 mmHg versus placebo at 12 weeks, with early effects by week 4. Hyperkalemia (>6.0 mmol/L) occurred in 5–7% of lorundrostat recipients, none with placebo.
Key Findings
- Placebo-adjusted reduction in 24-hour systolic BP at 12 weeks: −7.9 mmHg (50 mg stable dose) and −6.5 mmHg (dose-adjustment arm).
- Early BP lowering at 4 weeks in combined lorundrostat groups: −5.3 mmHg vs placebo.
- Hyperkalemia >6.0 mmol/L occurred in 5–7% of lorundrostat patients; 0% in placebo.
Clinical Implications
Lorundrostat may emerge as a targeted option for resistant hypertension with meaningful 24-hour BP reduction; potassium monitoring is essential due to hyperkalemia risk.
Why It Matters
This is the first robust RCT showing clinically meaningful ambulatory BP reduction with an aldosterone synthase inhibitor in treatment-resistant hypertension, published in NEJM.
Limitations
- Short 12-week treatment duration limits assessment of long-term efficacy and safety
- Sponsor-funded study; modest sample size (n=285) and hyperkalemia signal
Future Directions
Longer-term RCTs assessing cardiovascular outcomes, optimal monitoring/mitigation of hyperkalemia, and comparative effectiveness versus MRAs and other therapies.
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- I - Randomized, double-blind, placebo-controlled trial
- Study Design
- OTHER