Key result
Aldosterone synthase inhibitors lower SBP ~9 mmHg vs placebo but increase hypotension and hyperkalemia.
Why the study?
No head-to-head trials exist for aldosterone synthase inhibitors in resistant and uncontrolled hypertension, and their comparative efficacy and safety remain uncertain.
Do aldosterone synthase inhibitors reduce blood pressure in patients with uncontrolled and resistant hypertension?
Meta-Analysis (n=2,828)
Do aldosterone synthase inhibitors reduce blood pressure in patients with uncontrolled and resistant hypertension?
Aldosterone synthase inhibitors provide clinically meaningful blood pressure reductions in resistant and uncontrolled hypertension, but are associated with increased risks of hypotension, hyperkalemia, and hyponatremia.
Answers are grounded in this paper and cite their sources.
May add a novel option for resistant hypertension; confirms efficacy across agents while highlighting hypotension and hyperkalemia risks.
Background Aldosterone synthase inhibitors (ASIs) have emerged as a mechanistically targeted strategy for resistant and uncontrolled hypertension; however, no head-to-head trials exist, and comparative efficacy and safety remain uncertain. We compared their efficacy and safety using network and pairwise meta-analysis of randomized trials. Methods This systematic review and meta-analysis adhered to the PRISMA guidelines. PubMed/MEDLINE, Scopus, Embase, ClinicalTrials.gov, and Cochrane Library were searched from inception to January 14, 2026, for randomized trials evaluating ASIs versus placebo or standard care. A frequentist random-effects network meta-analysis assessed systolic (SBP) and diastolic blood pressure (DBP). Dichotomous safety outcomes were pooled using Hartung–Knapp random-effects models. Network consistency was evaluated using design-by-treatment interaction modeling. Prespecified subgroup analyses stratified outcomes by hypertension phenotype (resistant vs uncontrolled). Results Across 7 RCTs (n = 2,828), all ASIs significantly reduced SBP versus placebo: baxdrostat −8.63 mmHg (95% CI −10.84 to −6.42), lorundrostat −7.47 mmHg (95% CI −9.54 to −5.40), and LCI699/osilodrostat −5.63 mmHg (95% CI −9.15 to −2.12), with no significant indirect differences between agents. In resistant hypertension, lorundrostat (−9.00 mmHg; 95% CI −13.19 to −4.81) and baxdrostat (−8.77 mmHg; 95% CI −10.50 to −7.05) demonstrated pronounced reductions. In uncontrolled hypertension, LCI699/osilodrostat showed the largest point estimate (−10.55 mmHg; 95% CI −16.49 to −4.61), though this derives from a single early-phase trial and requires cautious interpretation. DBP reductions were significant for baxdrostat (−3.23 mmHg; 95% CI −4.73 to −1.73) and lorundrostat (−3.60 mmHg; 95% CI −5.43 to −1.77). Hypotension (RR 2.67), hyperkalemia (RR 7.94), and hyponatremia (RR 2.07) were significantly increased; serious adverse events, discontinuation, and network inconsistency were not detected. Conclusions ASIs provide clinically meaningful BP reduction across both hypertension phenotypes; however, short-term use is associated with hypotension and electrolyte disturbances, necessitating careful monitoring. Phenotype-specific efficacy and long-term safety require validation in outcome-driven trials.
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Yusuf et al. (2026) conducted a meta-analysis in Resistant and uncontrolled hypertension (n=2,828). Aldosterone synthase inhibitors vs. Placebo or standard care was evaluated on Systolic blood pressure (SBP) (MD -8.63 mmHg, 95% CI -10.84 to -6.42). Aldosterone synthase inhibitors significantly reduced systolic blood pressure versus placebo (e.g., baxdrostat -8.63 mmHg, 95% CI -10.84 to -6.42), but increased hypotension and hyperkalemia.
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