Efficacy and safety of lorundrostat in uncontrolled hypertension: a meta-analysis

Lorundrostat, a novel selective aldosterone synthase inhibitor, has emerged as a potential treatment for uncontrolled hypertension. However, a comprehensive summary of its efficacy and safety profile is currently lacking. This meta-analysis aims to synthesize evidence from published randomized controlled trials (RCTs) to evaluate the clinical benefits and risks of lorundrostat in this patient population. Following the PRISMA guidelines, a systematic search was conducted on PubMed, Scopus, and Web of Science for RCTs comparing lorundrostat with placebo. The primary outcomes were changes from baseline in systolic and diastolic blood pressure. Data were pooled using a random-effects model to calculate mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes, with corresponding 95% confidence intervals (CIs). Three RCTs comprising 1568 patients were included. Compared to placebo, lorundrostat significantly reduced both 24-h systolic blood pressure (MD: - 6.65 mmHg; 95% CI: [- 9.95 to - 3.35]) and office systolic blood pressure (MD: - 7.94 mmHg; 95% CI: [- 9.72 to - 6.15]). While the risk of serious adverse events was comparable, lorundrostat was associated with a higher incidence of hyperkalemia (RR: 5.47; 95% CI: [1.55 to 19.36]) and hyponatremia (RR: 1.95; 95% CI: [1.13 to 3.36]). Notably, lorundrostat significantly reduced the risk of adrenal insufficiency (RR: 0.15; 95% CI: [0.03 to 0.91]). Lorundrostat may be an effective agent for lowering blood pressure in patients with uncontrolled hypertension. Its safety profile is acceptable but requires careful monitoring of serum electrolytes and renal function. The reduced risk of adrenal insufficiency highlights its selectivity and potential as a valuable therapeutic option. Further large-scale, long-term studies are needed to confirm its sustained benefits and safety.