Optimal Dose of Lorundrostat in Uncontrolled Hypertension: A Dose Response Meta-Analysis

Background Lorundrostat, an aldosterone synthase inhibitor, shows promise for hypertension management, though optimal dosing strategies remain poorly defined. Aims To evaluate the efficacy, safety, and dose-response effects of Lorundrostat to identify the optimal therapeutic dose. Methods We searched PubMed, Embase, Scopus, and ClinicalTrials.gov systematically for relevant RCTs. Using a random-effects model, data were pooled to calculate mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs). Dose-response modeling was performed using “dosresmeta” and “rcs” packages in R (v4.4.3). Results Three RCTs (n=1568) were included. Lorundrostat significantly reduced systolic BP at 4–8 weeks (MD: –7.66 mmHg, 95% CI: –10.42 to –4.89) and 12 weeks (MD: –10.19 mmHg, 95% CI: –13.57 to –6.82). Diastolic BP also decreased significantly (MD: –3.81). Sub-group analysis based on background medication count showed no significant differences (P=0.80). Aldosterone levels were significantly reduced (MD: –4.39). Dose-response modeling identified 60 mg as the optimal dose, with diminishing returns thereafter. While hyperkalemia risk increased (RR: 3.19), no significant differences were found in serious adverse events. Conclusion Lorundrostat effectively lowers BP with a manageable safety profile. The modeling-based insights suggest 60 mg as the optimal dose, delineating a clearer therapeutic window.