Aldosterone synthase inhibitors significantly reduced office systolic blood pressure compared with placebo (MD -8.58 mmHg; 95% CI -9.91 to -7.25).
Meta-Analysis (n=2,639)
Yes
Do aldosterone synthase inhibitors reduce office systolic blood pressure in adults with uncontrolled or treatment-resistant hypertension?
Aldosterone synthase inhibitors effectively reduce blood pressure in uncontrolled hypertension but are associated with renal function decline and electrolyte disturbances, necessitating careful monitoring.
Mean Difference: -8.58 (95% CI -9.91–-7.25)
Objective: Resistant and uncontrolled hypertension remains a major global health challenge and contributes to cardiovascular morbidity and mortality. Aldosterone synthase inhibitors (ASIs) are a novel class of antihypertensive drugs targeting CYP11B2, with potential benefits in treatment-resistant and uncontrolled hypertension. However, their comparative efficacy and safety remain uncertain. Design and method: We systematically searched through PubMed, Scopus, Cochrane, and Web of Science (WOS) from inception to September 6, 2025, for randomized controlled trials (RCTs) evaluating ASIs versus placebo in adults with uncontrolled or treatment-resistant hypertension. The primary outcome was the change in office systolic blood pressure (OSBP). Secondary outcomes included changes in office diastolic blood pressure (ODBP), ambulatory SBP (ASBP), serum aldosterone, plasma renin activity (PRA), potassium and sodium levels, and estimated glomerular filtration rate (eGFR). Random-effects pairwise and network meta-analyses were performed. Results: Five RCTs comprising 2,639 patients across 29 countries were included. ASIs significantly reduced OSBP compared with placebo (mean difference MD –8.58 mmHg; 95% CI –9.91 to –7.25; I2 = 0%). baxdrostat 2 mg achieved the greatest reduction in OSBP (MD –10.32 mmHg; 95% CI –13.50 to –7.14), ODBP (MD –4.27 mmHg), and ambulatory SBP (MD –17.00 mmHg). ASI therapy lowered serum aldosterone and increased PRA, confirming target engagement. ASIs were associated with reduced eGFR (MD –6.88 mL/min/1.73 m2). Dose-dependent risks were most pronounced with lorundrostat 100 mg. Conclusions: ASIs, particularly baxdrostat 2 mg, reduce blood pressure effectively in patients with uncontrolled hypertension, with consistent effects on aldosterone and renin. However, their use is limited by renal function decline, electrolyte disturbances at higher doses. Careful dose selection and monitoring are essential.
Elkasaby et al. (Fri,) conducted a meta-analysis in uncontrolled or treatment-resistant hypertension (n=2,639). Aldosterone synthase inhibitors vs. placebo was evaluated on change in office systolic blood pressure (OSBP) (MD -8.58, 95% CI -9.91 to -7.25). Aldosterone synthase inhibitors significantly reduced office systolic blood pressure compared with placebo (MD -8.58 mmHg; 95% CI -9.91 to -7.25).