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. 2025 Sep 22:16:1664810.
doi: 10.3389/fphar.2025.1664810. eCollection 2025.

Efficacy and safety of aldosterone synthase inhibitors for uncontrolled hypertension: a meta-analysis of randomized controlled trials and systematic review

Yifan Gao  1 , Xu Mu  1 , Xingxue Pang  1   2
Affiliations

Efficacy and safety of aldosterone synthase inhibitors for uncontrolled hypertension: a meta-analysis of randomized controlled trials and systematic review

Yifan Gao et al. Front Pharmacol. .

Abstract

Background: Uncontrolled hypertension is a major global health concern. Aldosterone synthase inhibitors (ASIs) show promise as a new treatment approach for blood pressure management.

Methods: A systematic review and meta-analysis were conducted on randomized controlled trials comparing ASIs versus placebo for uncontrolled hypertension. The search included PubMed, Cochrane Library, Web of Science, and Embase databases from inception to 7 July 2025, limited to English-language publications. Data extraction was performed independently by two authors.

Results: Four randomized controlled trials involving 1,838 patients (mean age 62 years; 47% female) were analyzed. The results demonstrated that ASIs significantly reduced office systolic blood pressure by 8.21 mmHg (95% CI, -10.64 to -5.78; P < 0.0001) and diastolic blood pressure by 3.64 mmHg (95% CI, -5.65 to -1.63; P = 0.0004). The risk ratio for adverse events was 1.42 (95% CI, 1.25-1.60; P < 0.00001), with a similar trend observed for serious adverse events (risk ratio 1.17; 95% CI, 0.63-2.17; P = 0.61). No treatment-related deaths occurred. However, ASIs were associated with a significantly higher risk of hyperkalemia (risk ratio 7.97; 95% CI, 2.27-27.99; P = 0.001).

Conclusion: ASIs significantly lower blood pressure in hypertensive patients with an acceptable safety profile, though hyperkalemia risk requires monitoring. These results suggest ASIs may be a viable hypertension treatment, but larger studies are needed.

Keywords: aldosterone synthase inhibitors; blood pressure reduction; hyperkalemia; meta-analysis; uncontrolled hypertension.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of the article selection procedure for meta-analysis.
FIGURE 2
FIGURE 2
Pooled treatment effect estimates of aldosterone synthase inhibitors compared with placebo on systolic blood pressure in patients with uncontrolled hypertension, random-effects model.
FIGURE 3
FIGURE 3
Pooled treatment effect estimates of aldosterone synthase inhibitors compared with placebo on diastolic blood pressure in patients with uncontrolled hypertension, random-effects model.
FIGURE 4
FIGURE 4
Pooled safety effect estimates of aldosterone synthase inhibitors compared with placebo in patients with uncontrolled hypertension, random-effects model.
See this image and copyright information in PMC

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