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Review
. 2025 Sep;8(5):e70094.
doi: 10.1002/edm2.70094.

Efficacy and Safety of Aldosterone Synthase Inhibitors in Hypertension: A Systematic Review and Meta-Analysis

Jia Shen Goh  1 , Sameen Sohail  2 , Haroon Ayub  3   4 , Zian Zafar Cheema  5 , Nitish Behary Paray  6 , Sanka Adikari  7 , Ahmad Mesmar  8 , Mohammad Atout  9 , Abdul Rehman Qazi  10 , Ahmad Aldalqamouni  11 , Bilal Younas  12 , Muhammad Atif Rauf  13 , Muhammad Azhar Waheed Khan  14 , Aya Abouayana  8 , Ahmed Eid Ahmed Abouayana  15 , Ali Hasan  16 , Maryam Shahzad  17 , Mushood Ahmed  18 , Raheel Ahmed  19   20 , Saeed Ahmed  21
Affiliations
Review

Efficacy and Safety of Aldosterone Synthase Inhibitors in Hypertension: A Systematic Review and Meta-Analysis

Jia Shen Goh et al. Endocrinol Diabetes Metab. 2025 Sep.

Abstract

Background: Hypertension remains a major contributor to global cardiovascular morbidity and mortality. Aldosterone, a key hormone in blood pressure regulation, plays a significant role in hypertension pathophysiology. This has led to growing interest in aldosterone synthase inhibitors (ASIs) as a potential treatment. This meta-analysis aims to evaluate the efficacy and safety of ASIs in managing hypertension.

Methods: A systematic search of PubMed, Google Scholar and Cochrane Central was conducted up to 13 July 2025, to identify randomised controlled trials (RCTs) evaluating ASIs in hypertensive adults. Data were analysed using RevMan version 5.4, employing random-effects models with significance set at p < 0.05.

Results: A total of 8 RCTs were included, with a total of 2003 participants in the ASI group and 650 participants in the placebo group. ASIs significantly reduced systolic blood pressure (SBP) compared to placebo (MD: -6.01 mmHg; 95% confidence interval [CI]: -9.31 to -2.71; I2 = 85%; p = 0.0004); diastolic blood pressure (DBP) was found to be comparable between the two groups (MD: -2.20 mmHg; 95% CI: -4.46 to 0.06; I2 = 69%; p = 0.06). There was a significant reduction in serum aldosterone levels favouring ASI use (MD: -1.46; 95% CI: -2.76 to -0.16; I2 = 99%; p < 0.00001). The risk of serious (RD: 0.00; 95% CI: -0.01 to 0.02; I2 = 30%; p = 0.75) and non-serious adverse events (RD: 0.05; 95% CI: -0.02 to 0.12; I2 = 64%; p = 0.20) did not differ significantly between ASI and placebo groups. However, ASI use was associated with a significantly higher risk of hyperkalemia (RD: 0.04; 95% CI: 0.02 to 0.06; I2 = 70%; p = 0.002).

Conclusion: ASIs effectively lower SBP and serum aldosterone in adults with hypertension. They appear safe overall but may increase the risk of hyperkalemia.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA chart depicting the study selection process.
FIGURE 2
FIGURE 2
Forest plot for the outcome of Reduction in SBP.
FIGURE 3
FIGURE 3
Forest plot for the outcome of Reduction in DBP.
FIGURE 4
FIGURE 4
Forest plot for the outcome of any serious adverse event.
FIGURE 5
FIGURE 5
Forest plot for the outcome of non‐serious adverse event.
FIGURE 6
FIGURE 6
Forest plot for the outcome of changes in serum aldosterone.
FIGURE 7
FIGURE 7
Forest plot for the outcome of Hyperkalemia.
See this image and copyright information in PMC

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