Efficacy and safety of lorundrostat in uncontrolled hypertension: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

Hypertension remains a leading global health concern, contributing significantly to cardiovascular and renal morbidity and mortality. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of lorundrostat, a selective aldosterone synthase inhibitor, in adults with uncontrolled hypertension, synthesizing evidence from randomized controlled trials. We systematically searched PubMed, Embase, and Cochrane Central from inception to July 2025. A total of three RCTs comprising 1,567 participants (1,164 receiving lorundrostat and 403 receiving placebo) were included. Lorundrostat significantly reduced office systolic blood pressure compared to placebo (MD: -7.93 mm Hg; 95% CI: -13.62, -2.24; p = 0.006), with no significant impact on office diastolic blood pressure or 24-h ambulatory blood pressure. The risk of adverse events was higher with lorundrostat (RR: 1.47; 95% CI: 1.29, 1.67; p < 0.0001), particularly mild adverse events. Lorundrostat demonstrates moderate efficacy in lowering office systolic blood pressure and reducing the incidence of severely elevated blood pressure in adults with uncontrolled hypertension. However, its use is associated with a higher incidence of mild adverse events, hyperkalemia, and hyponatremia. Larger and longer-term trials are warranted to further clarify the role of lorundrostat in hypertension management and to better define its safety profile.