Key result
Aldosterone synthase inhibitors lower systolic blood pressure by ~7 mmHg but increase hyperkalemia risk.
Why the study?
Prior meta-analyses of aldosterone synthase inhibitors for hypertension were limited by heterogeneous evidence and incomplete safety assessment, necessitating an updated synthesis including new RCTs.
Do aldosterone synthase inhibitors reduce blood pressure in patients with uncontrolled or resistant hypertension?
Meta-Analysis (n=3,595)
Do aldosterone synthase inhibitors reduce blood pressure in patients with uncontrolled or resistant hypertension?
Mean Difference: -6.84 (95% CI -8.76–-4.93)
Aldosterone synthase inhibitors provide clinically meaningful short-term blood pressure reduction in hypertension but are associated with significant increases in hyperkalemia, hyponatremia, and hypotension.
Aldosterone synthase inhibitors merit consideration for resistant hypertension with monitoring; extends prior RCTs by quantifying hyperkalaemia and hypotension risks in 3595 patients.
Background Prior meta-analyses of aldosterone synthase inhibitors (ASIs) for hypertension were limited by heterogeneous evidence and incomplete safety assessment. New randomised controlled trials (RCTs), including BaxHTN, required an updated synthesis. Methods MEDLINE, PubMed, Embase, and Cochrane CENTRAL were searched through January 2026 for placebo-controlled RCTs of ASIs for hypertension. Random-effects models pooled mean differences in systolic and diastolic blood pressure (BP) and risk ratios (RRs) for safety, with 95% confidence intervals (CIs). Principal systolic BP combined office and 24-h ambulatory measurements; office-only analysis was post hoc. Results Nine RCTs (10 independently randomised cohorts; 3595 participants) were included. ASIs reduced systolic BP (mean difference (MD) −6.84 mmHg; 95% CI −8.76 to −4.93) and diastolic BP (MD −2.99 mmHg; 95% CI −4.22 to −1.76). Office-only systolic BP results were similar (MD −6.64 mmHg; 95% CI −8.97 to −4.32). Intermediate- and high-dose estimates were numerically greater than the low-dose estimate, but interaction was nonsignificant ( P = 0.25). ASIs increased hyperkalaemia (RR 2.74; 95% CI 1.59–4.71), hyponatraemia (RR 1.81; 95% CI 1.11–2.95), hypotension (RR 2.76; 95% CI 1.29–5.93), and at least one adverse event (RR 1.22; 95% CI 1.05–1.42). Serious adverse events did not differ significantly (RR 0.98; 95% CI 0.59–1.62). Certainty was high for BP and at least one adverse event and moderate for other safety outcomes. Conclusion ASIs provide clinically meaningful short-term BP reduction in uncontrolled or resistant hypertension but increase electrolyte abnormalities, hypotension, and adverse events. Monitoring is warranted; long-term cardiovascular, renal, and safety outcomes remain uncertain.
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Kashyap et al. (2026) conducted a meta-analysis in hypertension (n=3,595). Aldosterone synthase inhibitors (ASIs) vs. Placebo was evaluated on Systolic blood pressure (combined office and 24-h ambulatory measurements) (MD -6.84 mmHg, 95% CI -8.76 to -4.93). Aldosterone synthase inhibitors significantly reduced systolic blood pressure (MD -6.84 mmHg; 95% CI -8.76 to -4.93) but increased risks of hyperkalaemia, hyponatraemia, and hypotension.
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