Key result
Aldosterone synthase inhibitors lower systolic BP by ~9 mmHg vs. placebo in hypertension.
Why the study?
Aldosterone overproduction is an important cause of uncontrolled or resistant hypertension, and while MRAs block downstream signaling, aldosterone synthase inhibitors such as baxdrostat and lorundrostat act upstream to reduce adrenal aldosterone production, prompting a synthesis of recent RCT evidence.
Do aldosterone synthase inhibitors (baxdrostat and lorundrostat) reduce systolic and diastolic blood pressure in adults with uncontrolled or resistant hypertension?
Meta-Analysis
Randomized controlled trials
Do aldosterone synthase inhibitors (baxdrostat and lorundrostat) reduce systolic and diastolic blood pressure in adults with uncontrolled or resistant hypertension?
Aldosterone synthase inhibitors such as baxdrostat and lorundrostat produce clinically meaningful short-term reductions in systolic and diastolic blood pressure in patients with uncontrolled or resistant hypertension, though direct comparisons with standard mineralocorticoid receptor antagonists are still needed.
Answers are grounded in this paper and cite their sources.
Supports ASI for resistant hypertension; confirms efficacy across randomized trials.
Background: The overproduction of aldosterone is an important cause of uncontrolled or resistant hypertension. Conversely, aldosterone synthase inhibitors including baxdrostat and lorundrostat have an upstream effect blocking aldosterone synthesis. The overproduction of aldosterone causes many drug resistant hypertensive diseases. Agents that act at the Mineralocorticoid Receptor (MR), i.e., MR Antagonists (MRAs) such as spironolactone and eplerenone block signalling downstream of aldosterone, thereby inducing BP lowering effects. Conversely, aldosterone synthase inhibitors inculding baxdrostat and lorundrostat have an upstream effect at the aldosterone level, thereby specifically reducing the production of aldosterone in the adrenal cortex. Objective: This systematic review and meta-analysis of recent (2020-2025) RCTs on blood pressure-lowering evidence for ASIs and established MRAs. The 2020-2025 records published were included in accordance with PRISMA 2020 orientation (Pubmed, Scopus, Web of Science, Cochrane CENTRAL, ClinicalTrials.gov). Eligible recent (2020-2025) randomized controlled trials in adults with hypertension reporting impact on Systolic Blood Pressure (SBP) or Diastolic Blood Pressure (DBP) were included. Placebo-adjusted mean differences in mmHg data was assessed, using random-effects meta-analysis where summary confidence intervals available. Outcomes: Eight contemporary RCT reports qualified for qualitative synthesis and five ASI RCT reports were incorporated as dose-level estimates in quantitative synthesis. The combined effect of ASI was a reduction in SBP by almost -8.82 mmHg (95% CI, -10.46 to -7.18; I2 from dose-level summaries = moderate) and a reduction in DBP by almost -4.25 mmHg (95% CI, -5.33 to -3.18). The two drugs, Baxdrostat and lorundrostat, produced clinically meaningful reductions, especially in those with uncontrolled or resistant hypertension. No new 2020-2025 RCT directly comparing spironolactone or eplerenone against ASIs was identified; therefore, class comparison is indirect and must be interpreted cautiously. Overall, ASIs have strong short-term placebo-adjusted effects on BP. MRAs are the standard add-on therapy of resistant hypertension, but direct RCT comparisons between ASIs and MRAs are required.
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Ray et al. (2026) conducted a meta-analysis in Uncontrolled or resistant hypertension. Aldosterone synthase inhibitors (baxdrostat and lorundrostat) vs. Placebo (with indirect comparison to mineralocorticoid receptor antagonists) was evaluated on Placebo-adjusted mean difference in Systolic Blood Pressure (SBP) (MD -8.82 mmHg, 95% CI -10.46 to -7.18). Aldosterone synthase inhibitors reduced placebo-adjusted systolic BP by -8.82 mmHg (95% CI -10.46 to -7.18) and diastolic BP by -4.25 mmHg (95% CI -5.33 to -3.18) in hypertension.
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