Efficacy and Safety of Aldosterone Synthase Inhibitors for Hypertension: A Meta-Analysis of Randomized Controlled Trials and Systematic Review

BACKGROUND: Hypertension is a major global health issue. Aldosterone synthase inhibitors (ASIs) have emerged as a promising therapeutic strategy for blood pressure control. METHODS: A thorough search of the MEDLINE and Embase databases up to March 30, 2024, identified randomized trials comparing ASIs with a placebo for hypertension treatment. Data extraction was done independently by 2 authors. Both random-effects (REML) and fixed-effects meta-analyses were conducted to account for diversity and study size, respectively. Risk ratios for binary outcomes and mean differences for continuous outcomes were calculated. RESULTS: Seven randomized controlled trials involving 1440 patients (mean age, 60 years; 39% women) were included. The analysis showed that ASIs reduced office systolic blood pressure by 6.3 mm Hg ([95% CI, –8.8 to –3.8]; P <0.0001) and diastolic blood pressure by 2.2 mm Hg ([95% CI, –4.2 to –0.2]; P =0.03). The risk ratio for adverse events was 1.1 ([95% CI, 0.9–1.2]; P =0.3), with a similar trend for serious adverse events (risk ratio, 1.0 [95% CI, 0.5–2.3]; P =0.95). No treatment-related deaths occurred. However, the risk of hyperkalemia was higher with ASIs (risk ratio, 2.5 [95% CI, [1.2–5.4]; P <0.02). CONCLUSIONS: ASIs effectively reduce systolic and diastolic blood pressure in hypertensive patients and have a tolerable safety profile. The increased risk of hyperkalemia requires careful monitoring. These findings suggest ASIs are a potential treatment option for hypertension, pending further research in larger studies.