Second-Generation Aldosterone Synthase Inhibitors for Hypertension

BACKGROUND: Second-generation aldosterone-synthase inhibitors (ASIs) may offer a novel treatment for hypertension. OBJECTIVES: The objective of the study was to assess the efficacy and safety of ASIs in this clinical setting. METHODS: We searched major databases for randomized controlled trials (RCTs) assessing ASIs (baxdrostat, lorundrostat, and vicadrostat) in patients with hypertension. For efficacy outcomes, mean differences (MD) with 95% credible intervals (CrIs) were estimated using a Bayesian random-effects model. For adverse events, OR with 95% CrI were estimated using a Bayesian binomial-normal hierarchical model. The protocol was registered in Prospective Register of Systematic Reviews (CRD420251132306). RESULTS: 0.1). In subgroup analysis, the probability of achieving a clinically meaningful reduction in SBP (MD < -5 mm Hg) was 87.5% with baxdrostat and 94.3% with lorundrostat. CONCLUSIONS: Second-generation ASIs had a high likelihood of a clinically significant reduction in SBP compared with placebo. However, hyperkalemia, hyponatremia, and hypotension were more frequent with ASIs.