BACKGROUND AND PURPOSE:

• Lorundrostat is an aldosterone synthase inhibitor that may help treat hypertension
• Laffin et al. (NEJM, 2025) examined the efficacy and safety of lorundrostat in participants with uncontrolled and treatment-resistant hypertension

METHODS:

• Multicenter, double-blind, randomized, placebo-controlled trial
• Participants
  • Individuals receiving 2 to 5 antihypertensive medications
  • BP ≥140/90 mm Hg obtained during an office visit
  • Average 24-hour ambulatory blood pressure of ≥130/80 mm Hg
• Interventions
  • Stable dose group: Lorundrostat, 50 mg daily
  • Dose adjustment group: Lorundrostat, starting dose of 50 mg daily, increased to 100 mg daily if systolic blood pressure was ≥130 mm Hg after 4 weeks
  • Placebo
• Study design
  • Patients stopped their regular medications and were assigned standardized doses antihypertensive medications based on number of medications prior to enrollment
    • If taking 2 medications: Olmesartan with indapamide or hydrochlorothiazide
    • If taking ≥3 medications: Amlodipine added to the above
  • Changes in blood pressure were assessed as the least-squares mean difference from placebo (the placebo-adjusted change) in each lorundrostat group
• Primary outcome
  • Change in 24-hour average systolic blood pressure from baseline to week 12
• Secondary outcome
  • Change in 24-hour average systolic blood pressure from baseline to week 4

RESULTS:

• Stable dose: 94 participants | Dose adjustment: 96 participants | Placebo: 95 participants
  • Mean age: 60 years | Black: 53%
• Compared to placebo, both lorundrostat groups achieved greater change in 24-hour average systolic blood pressure at 12 weeks
  • Stable dose vs placebo
    • Stable dose: −15.4 mm Hg | Placebo: −7.4 mm Hg
    • Placebo-adjusted change −7.9 mm Hg (97.5% CI, −13.3 to −2.6)
  • Dose adjustment vs placebo
    • Dose adjustment: −13.9 mm Hg
    • Placebo-adjusted change −6.5 mm Hg (97.5% CI, −11.8 to −1.2)
• Both lorundrostat groups also achieved greater change in 24-hour average systolic blood pressure at 4 weeks
  • Placebo-adjusted change: −5.3 mm Hg (95% CI, −8.4 to −2.3)
• Incidence of potassium levels >6.0 mmol per liter
  • Stable dose: 5% | Dose adjustment: 7% | Placebo: 0

CONCLUSION:

• For patients with uncontrolled, treatment-resistant hypertension, lorundrostat improved 24-hour average blood pressure at 4 and 12 weeks vs placebo
• Limitations include on 12 week follow-up | Open label study is ongoing
• The authors state

In this trial, aldosterone synthase inhibition with lorundrostat effectively lowered blood pressure in patients with uncontrolled and treatment-resistant hypertension

Learn More – Primary Sources:

Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension

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