Efficacy and Safety of Lorundrostat in Uncontrolled and/or Treatment Resistant Hypertension: A Systematic Review and...

Resistant hypertension (RH) persists despite use of three different antihypertensive drug classes. Additionally, people with persistent hypertension despite the use of multiple drugs, who do not fit the RH criteria are said to have uncontrolled hypertension. Both these populations have increased risk of cardiovascular, CNS, and renal complications. Aldosterone plays a key role in RH and uncontrolled hypertension. Lorundrostat, a selective aldosterone synthase inhibitor targeting CYP11B2 enzyme, shows promise in improving blood pressure control in these populations.

To evaluate lorundrostat's efficacy and safety in uncontrolled and treatment-resistant hypertension through a meta-analysis of randomized controlled trials.

We searched PubMed, Cochrane, Google Scholar, and clinicaltrials.gov through July 2025. Screening was done via rayyan.ai; data analyzed with Review Manager 5.4. Risk of bias and evidence certainty used Cochrane Risk of Bias 2.0 and GRADE.

Three high-quality RCTs with 1426 patients were included. Stable dose lorundrostat significantly reduced mean systolic blood pressure compared to placebo (MD = - 9.81 mmHg; 95% CI [- 12.80, - 6.83]; p < 0.00001) and dose-adjusted lorundrostat also showed reduction (MD= - 7.35; 95% CI [- 10.81, - 3.89]; p < 0.0001). Adverse events; hypotension, hyponatremia, hyperkalemia, and reduced GFR were more frequent with lorundrostat, while hypertension-related events were more common in placebo. Certainty of evidence was high (except for any adverse event), and heterogeneity was low across outcomes (except for any adverse event with dose adjustment).

Lorundrostat effectively reduces systolic BP in uncontrolled and resistant hypertension but requires cautious monitoring due to safety concerns.