Efficacy and Safety of Lorundrostat in Patients With Uncontrolled and Treatment-Resistant Hypertension: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis evaluated the efficacy and safety of lorundrostat, a novel aldosterone synthase inhibitor, in patients with uncontrolled or treatment-resistant hypertension. A comprehensive literature search was conducted across major electronic databases, including MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus through July 25, 2025. Randomized controlled trials comparing lorundrostat to placebo in adult patients with uncontrolled hypertension were included. Three studies met the inclusion criteria and were analyzed using Review Manager 5.4.1 (The Cochrane Collaboration, London, England, UK) with random-effects models. The pooled analysis demonstrated that lorundrostat achieved a statistically significant reduction in systolic blood pressure of 8.04 mmHg compared to placebo (95% confidence interval (CI): -10.69 to -5.39) with low heterogeneity (I2 = 28%). Subgroup analysis revealed comparable efficacy between 50 mg and 100 mg doses, suggesting a relatively flat dose-response relationship within this range. This magnitude of blood pressure reduction is clinically meaningful and comparable to established fourth-line therapies like spironolactone. Regarding safety, lorundrostat was associated with a significantly higher risk of adverse events compared to placebo (risk ratio (RR): 1.47; 95% CI: 1.32 to 1.64), though most were mild to moderate in severity. Importantly, no significant difference was observed in serious adverse events (RR: 1.01; 95% CI: 0.39 to 2.63), providing reassurance about the overall safety profile. These findings suggest that lorundrostat represents a promising therapeutic option for treatment-resistant hypertension, offering clinically significant blood pressure reductions with an acceptable safety profile. However, long-term cardiovascular outcome studies and direct comparisons with existing therapies are needed to fully establish its clinical role.