Comparing Efficacy and Safety of Different Aldosterone Synthase Inhibitors for Hypertension: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials
Key result
Aldosterone synthase inhibitors, particularly baxdrostat and lorundrostat, significantly lower BP but increase hyperkalemia risk.
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Why the study?
Hypertension affects over 1.3 billion people globally with many remaining uncontrolled, leading to the emergence of aldosterone synthase inhibitors as a treatment.
Do different aldosterone synthase inhibitors reduce blood pressure in hypertensive patients?
Key Points
- The study aims to evaluate the effectiveness and safety of various aldosterone synthase inhibitors in treating hypertension.
- Conducted a systematic review and network meta-analysis on randomized controlled trials.
- Searched databases including PubMed, Cochrane Central, and ScienceDirect until December 2025.
- Used frequentist network meta-analysis in RStudio with specific packages for analysis.
- Calculated P-scores for treatment ranking.
- Ten randomized controlled trials were analyzed.
- Baxdrostat 2 mg ranked best for reducing systolic blood pressure (SBP) with a P-score of 0.89.
- Lorundrostat 50 mg once daily was identified as the best for reducing diastolic blood pressure (DBP) with a P-score of 0.84.
- Increased risk of hyperkalemia was noted with Baxdrostat and lorundrostat regimens.
- Symptomatic hypotension was mainly reported with lorundrostat 50 mg daily.
Study Design
Type
Meta-Analysis
Structured PICO
Do different aldosterone synthase inhibitors reduce blood pressure in hypertensive patients?
P
Population
Hypertensive patients (pooled from 10 RCTs)
I
Intervention
Aldosterone synthase inhibitors (ASIs) including 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), and vicadrostat (10, 20, and 3 mg plus empagliflozin, and 20 mg)
C
Comparator
Other ASI regimens (network meta-analysis)
O
Outcome
Reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP)surrogate
Baxdrostat and lorundrostat regimens significantly reduce systolic and diastolic blood pressure in hypertensive patients, though they are associated with an increased risk of hyperkalemia.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“We know that aldosterone not only raises BP but it is detrimental to our vasculature and kidneys. Increasingly, we as a field in hypertension are understanding that excess aldosterone plays a role in a lot of patients with hypertension. Currently available mineralocorticoid receptor antagonist therapies like spironolactone and eplerenone can help, but newer drugs, such as lorundrostat, will probably be more beneficial in the long term.”
“I think that this is a promising new class of drugs, not only for hypertension, where there's a need for innovation, but it could also be used in things like heart failure and chronic kidney disease, as well, because we know that aldosterone has a negative impact on the vasculature and a negative impact on the kidneys. So the sky's the limit with this new class of medicines.”
Implication
Requires hyperkalemia monitoring with baxdrostat and lorundrostat in hypertension; extends evidence for aldosterone synthase inhibitors.
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.
Discussion
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Cite This Study
Waseem et al. (2026) conducted a meta-analysis in Hypertension. Aldosterone synthase inhibitors (baxdrostat, lorundrostat, osilodrostat, vicadrostat) was evaluated on Systolic blood pressure (SBP) and diastolic blood pressure (DBP). Aldosterone synthase inhibitors, particularly baxdrostat 2 mg (P-score=0.89) and lorundrostat 50 mg (P-score=0.84), significantly reduced blood pressure, though hyperkalemia risk increased.