Comparing Efficacy and Safety of Different Aldosterone Synthase Inhibitors for Hypertension: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

Abstract

Background: Hypertension affects over 1.3 billion globally, many remain uncontrolled, and aldosterone synthase inhibitors (ASIs) are emerging as a treatment. This network meta-analysis compared the effectiveness and safety of ASI regimens in hypertensive patients.

Methods: PubMed, Cochrane Central, and ScienceDirect were searched till December 2025. We conducted a frequentist network meta-analysis using RStudio version 4.3.3 with the "meta" and "netmeta" packages. P-scores were used for treatment ranking.

Results: Ten randomized controlled trials were included in the analysis. Baxdrostat 1 mg, 2 mg, lorundrostat 100 mg once daily, 12.5 mg twice daily, 25 mg twice daily, 50 mg once daily, 50 mg and escalation to 100 mg, osilodrostat 0.25, 0.5, and 1.0 mg once daily, vicadrostat 10, 20, and 3 mg plus empagliflozin, and 20 mg significantly reduced the systolic blood pressure (SBP), where the baxdrostat 2 mg (P-score = 0.89) was ranked best. Lorundrostat 50 mg once daily, Baxdrostat 1 and 2 mg significantly reduced the diastolic blood pressure (DBP) with Lorundrostat 50 mg once daily ranked best (P-score = 0.84). Adverse events were increased with lorundrostat regimens, but serious adverse events were similar across regimens. Hyperkalemia was more frequent with Baxdrostat 1 and 2 mg and all lorundrostat regimens. Symptomatic hypotension occurred mainly with lorundrostat 50 mg daily.

Conclusion: The SBP and DBP were significantly reduced with the baxdrostat and lorundrostat regimens, although the risk of hyperkalemia increased. Adverse events were also higher in the lorundrostat regimens, whereas serious adverse events were comparable.