Safety and Efficacy of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-Analysis

Uncontrolled hypertension remains a major global health concern and a leading cause of cardiovascular morbidity and mortality. Aldosterone dysregulation plays a critical role in resistant hypertension, and Lorundrostat, a novel aldosterone synthase inhibitor, offers a promising therapeutic approach by directly inhibiting aldosterone production. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Lorundrostat in adults with uncontrolled hypertension. Comprehensive searches of MEDLINE (PubMed), ScienceDirect, Google Scholar, and Cochrane databases were conducted up to July 2025 following PRISMA guidelines, with the protocol registered on PROSPERO (CRD420251091117). Three randomized controlled trials involving 1,568 participants (1,165 Lorundrostat and 403 placebo) were included, all demonstrating low risk of bias. Pooled analysis revealed that Lorundrostat significantly reduced systolic blood pressure (-8.50 mmHg, 95% CI -11.63 to -5.36, p < 0.00001) and diastolic blood pressure (-3.53 mmHg, 95% CI -5.61 to -1.45, p = 0.0009) compared with placebo, with no heterogeneity observed. However, Lorundrostat was associated with higher risks of 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), though there were no significant differences in moderate or severe adverse events or reduction in kidney function. Publication bias was noted for diastolic blood pressure and selected safety outcomes. In conclusion, Lorundrostat demonstrates clinically meaningful blood pressure reduction in uncontrolled hypertension compared with placebo, but with an increased risk of electrolyte disturbances and hypotension. Cautious use and close monitoring are warranted, and larger, long-term trials are needed to further define its safety and therapeutic role.