Efficacy and safety of lorundrostat in patients with uncontrolled or resistant hypertension: A systematic review and meta-analysis with trial sequential analysis

Background

Uncontrolled hypertension (HTN) remains a challenge despite multiple anti-hypertensive medications. This study systematically evaluates the efficacy and safety of Lorundrostat, a novel aldosterone synthase inhibitor, in patients with uncontrolled hypertension.

Methods

A comprehensive search of major electronic databases was conducted until Jul 14, 2025, to identify randomized controlled trials (RCTs) comparing Lorundrostat with placebo. The primary outcomes included changes in office systolic and diastolic blood pressure (BP). A random-effects model was used to pool the data, presented as risk ratios (RR) or mean differences (MD) with 95 % confidence intervals (CIs).

Results

The pooled analysis of three RCTs comprising 1562 patients demonstrated that lorundrostat yielded statistically significant reductions in both office systolic BP (MD = −8.26 mmHg; 95 % CI: −10.87 to −5.64; p < 0.0001) and diastolic BP (MD = −3.53 mmHg; 95 % CI: −5.62 to −1.43; p = 0.001). However, Lorundrostat was associated with increased risks of hyperkalemia (RR = 7.93; 95 % CI: 1.55 to 40.64; p = 0.0131), hyponatremia (RR = 1.96; 95 % CI: 1.15 to 3.35; p = 0.0133), hypotension (RR = 3.06; 95 % CI: 1.15 to 8.11; p = 0.0250), and any adverse events (RR = 1.47; 95 % CI: 1.29 to 1.67; p < 0.0001).

Conclusion

Lorundrostat effectively controls blood pressure in patients with uncontrolled hypertension; however, it also increases the incidence of adverse events, and further large-scale trials are needed to confirm long-term efficacy and safety.

PROSPERO ID: CRD420251107424.