Efficacy and Safety of Baxdrostat in Hypertension: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials.
TL;DR
Findings strengthen the evidence for selective aldosterone synthase inhibition as a therapeutic approach for aldosterone-mediated hypertension and suggest that baxdrostat may provide an additional treatment option, particularly for patients who remain uncontrolled or cannot tolerate mineralocorticoid receptor antagonists.
Abstract
Background
Baxdrostat, a selective aldosterone synthase inhibitor, has emerged as a novel therapy for uncontrolled or resistant hypertension; however, randomized controlled trials (RCTs) have shown variable results.
Objective
To evaluate the efficacy and safety of baxdrostat compared with placebo or standard care in patients with uncontrolled or resistant hypertension.
Methods
We conducted a Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant systematic review and meta-analysis of RCTs. PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov were searched from inception to March 2026. Random-effects models were used to pool standardized mean differences (SMDs) and risk ratios (RRs). Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
Results
Five RCTs (n = 1724) were included. Baxdrostat significantly reduced systolic blood pressure (SMD = -0.40; 95% CI = -0.59 to -0.22; P < .001) and diastolic blood pressure (SMD = -0.29; 95% CI = -0.47 to -0.11; P = .001), and increased achievement of blood pressure control <130 mm Hg (RR = 2.08; 95% CI = 1.18-3.68; P < .001). It reduced serum sodium (SMD = -0.63; 95% CI = -0.80 to -0.47) but increased serum potassium (SMD = 0.91; 95% CI = 0.77-1.05), hyperkalemia (RR = 10.22; 95% CI = 4.22-24.73), and hyponatremia (RR = 2.90; 95% CI = 1.82-4.61). A modest decline in eGFR was observed (SMD = -0.49; 95% CI = -0.65 to -0.34). Serious adverse events and mortality were not significantly different. Evidence certainty was moderate to high.
Conclusion
AND RELEVANCE Baxdrostat significantly improves blood pressure control in patients with uncontrolled or resistant hypertension but increases the risk of hyperkalemia and other electrolyte disturbances. These findings strengthen the evidence for selective aldosterone synthase inhibition as a therapeutic approach for aldosterone-mediated hypertension and suggest that baxdrostat may provide an additional treatment option, particularly for patients who remain uncontrolled or cannot tolerate mineralocorticoid receptor antagonists. However, the increased risk of hyperkalemia and the limited duration of available trials highlight the need for careful electrolyte and renal monitoring and further studies evaluating long-term cardiovascular outcomes and comparisons with established therapies.