Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial
Authors' conclusion
Among individuals with uncontrolled hypertension, use of lorundrostat was effective at lowering blood pressure compared with placebo, which will require further confirmatory studies.
Study context
- Population
- Adults with uncontrolled hypertension taking ≥2 antihypertensive medications; initial cohort with suppressed plasma renin (PRA ≤1.0 ng/mL/h) and elevated plasma aldosterone (≥1.0 ng/dL), second cohort with PRA >1.0 ng/mL/h163 suppressed PRA + 37 not
- Participants
- 200 adults
- Comparison
- Lorundrostat vs placebo
- Primary endpoint
- Change in automated office SBP from baseline
- Follow-up
- Week 8
Methodological detailsplacebo-controlled, dose-ranging, Randomised July 2021–June 2022; final follow-up September 2022
- Placebo-controlled
- Dose-ranging
- Randomised July 2021–June 2022; final follow-up September 2022
Primary result
As reported in the abstract
Change in office SBP (suppressed PRA) · 8 weeks
Lorundrostat 100 mg once daily
−14.1
mm Hg
Lorundrostat 50 mg once daily
−13.2
mm Hg
Lorundrostat 12.5 mg once daily
−6.9
mm Hg
Placebo
−4.1
mm Hg
Lorundrostat 25 mg twice daily
−10.1
mm Hg
Lorundrostat 12.5 mg twice daily
−13.8
mm Hg
Each group vs placeboLeast-squares mean difference, mm Hg (90% CI)P value
Lorundrostat 50 mg once daily
−9.6(−15.8 to −3.4)
P = 0.01Lorundrostat 100 mg once daily
−7.8(−14.1 to −1.5)
P = 0.04Further findings
| Outcome | Values |
|---|---|
| Change in SBP, participants without suppressed PRA (second cohort) | Lorundrostat 100 mg once daily decrease 11.4 (SD 2.5) mm Hg |
Change in SBP, participants without suppressed PRA (second cohort)
- Similar to reduction with same dose in suppressed PRA
Safety
Serum potassium >6.0 mmol/L
- Participants with increase, corrected with dose reduction or discontinuation
- 6
Cortisol insufficiency
- No instances
Original publication
Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial. JAMA. Published 26 September 2023. doi:10.
Summarised from the published abstract; every number is checked against it