Efficacy and Safety of Lorundrostat for Uncontrolled and Treatment-resistant Hypertension: A Systematic Review and...

Uncontrolled hypertension remains a major contributor to cardiovascular morbidity and mortality. Lorundrostat directly reduces aldosterone synthesis and represents a targeted therapeutic strategy. The aim of this study was to evaluate the comparative efficacy and safety of lorundrostat among adults with uncontrolled or treatment-resistant hypertension. We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 guidelines and identified relevant randomized controlled trials from PubMed, ScienceDirect, and CENTRAL databases through August 2025. Data for various outcomes were extracted after computing the risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. We included 3 randomized controlled trials, with 1165 patients receiving lorundrostat and 403 patients receiving placebo. The efficacy outcomes demonstrated a significant reduction in systolic blood pressure (MD: -8.00; 95% CI: -10.81 to -5.19; P < 0.00001) and diastolic blood pressure (DBP) (MD: -3.31; 95% CI: -5.56 to -1.07; P = 0.004) with lorundrostat. Regarding safety outcomes, lorundrostat reported a higher incidence of adverse events (RR: 1.47; 95% CI: 1.29 to 1.67; P < 0.00001), hyperkalemia (RR: 9.17; 95% CI: 2.24 to 37.44; P = 0.002), and symptomatic hypotension (RR: 2.97; 95% CI: 1.12 to 7.90; P = 0.03), whereas the incidence of serious adverse events (RR: 1.29; 95% CI: 0.33 to 5.03; P = 0.71) was comparable between the 2 groups. Lorundrostat effectively reduced blood pressure; however, its use was accompanied by increased adverse events, hyperkalemia, and symptomatic hypotension. Efficacy must therefore be weighed carefully against safety, taking into account the patients' baseline characteristics.