Safety and Efficacy of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-analysis.
Saad Ashraf, Shariq A Wani, Muhammad Burhan et al.
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In 30 seconds
This systematic review and meta-analysis assessed lorundrostat’s efficacy and safety in adults with uncontrolled hypertension. It included three randomized controlled trials with 1,568 participants (1,165 receiving lorundrostat and 403 placebo). Compared with placebo, lorundrostat reduced systolic blood pressure by -8.50 mm Hg (95% confidence interval: -11.63 to -5.36, P < 0.00001) and diastolic blood pressure by -3.53 mm Hg (95% confidence interval: -5.61 to -1.45, P = 0.0009). The analysis also found higher risks of several adverse outcomes, including hyperkalemia and symptomatic hypotension.
Key findings
- Lorundrostat reduced systolic blood pressure by -8.50 mm Hg (95% confidence interval: -11.63 to -5.36, P < 0.00001) versus placebo.
- Diastolic blood pressure fell by -3.53 mm Hg (95% confidence interval: -5.61 to -1.45, P = 0.0009) versus placebo.
- Risks were higher for hyperkalemia (RR = 5.84, P = 0.01), symptomatic hypotension (RR = 2.98, P = 0.03), serious adverse events (RR = 3.31, P = 0.03), and hyponatremia (RR = 2.03, P = 0.01).
- There were no significant differences in moderate or severe adverse events or reduction in kidney function.
Why it matters
The findings suggest that aldosterone synthase inhibition can lower blood pressure in adults whose hypertension remains uncontrolled, while highlighting potential electrolyte and blood-pressure-related harms. These competing outcomes are relevant when weighing the treatment’s potential role and underscore the importance of safety assessment in future studies.
What to keep in mind
Only three trials were included, and publication bias was noted for diastolic blood pressure and selected safety outcomes. The abstract also identifies a need for larger, long-term trials to clarify safety and therapeutic role.