Baxdrostat for treatment of uncontrolled and resistant hypertension: a meta-analysis and systematic review

Background

Aldosterone synthase inhibitors (ASI) have recently emerged as alternative options for the treatment of uncontrolled and resistant hypertension. Baxdrostat, a highly selective ASI, has been studied in different trials, yielding mixed results. This meta-analysis aimed to summarize its effects on blood pressure and risk of hyperkalemia.

Methods

A systematic search was conducted on PubMed, Embase, Cochrane and unpublished data for randomized controlled trials (RCT) comparing baxdrostat to placebo for the treatment of patients with uncontrolled and resistant hypertension. The main efficacy outcome was reduction in systolic blood pressure (SBP) and the main safety outcome was the incidence of hyperkalemia. Baxdrostat arms were pooled for trials evaluating multiple doses. Pooled mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) were estimated using a random-effects model with the Restricted Maximum Likelihood estimator.

Results

Five RCTs with 1729 total patients were included. Baxdrostat significantly reduced SBP (MD -7.08 mmHg; 95% CI -11.68, -2.47; p = 0.01; I² = 73%) and DBP (MD -3.01 mmHg; 95% CI -5.7, -0.31; p = 0.04; I² = 64%) compared to placebo. There was, however, a significant increase in the incidence of hyperkalemia (RR 5.35; 95% CI 1.76, 16.25; NNH 19; I² = 0) and change in serum potassium (MD 0.4 mmol/L; 95% CI 0.26, 0.54).

Conclusions

Baxdrostat was effective in lowering systolic blood pressure, but increased the risk of hyperkalemia. These results support it as an alternative therapy for uncontrolled and resistant hypertension, with cautious use in patients at risk for hyperkalemia. New evidence is needed for long-term cardiovascular and renal outcomes, as well as comparisons with mineralocorticoid receptor antagonists and other ASIs, concerning efficacy and safety.

SBP forest plot HyperK forest plot