Comparative Efficacy of Aldosterone-Related Sodium-Retention Pathway Therapies for Resistant Hypertension: A Drug-Level Network Meta-Analysis of Randomized Controlled Trials
Abstract
Mineralocorticoid receptor antagonists (MRAs), aldosterone synthase inhibitors (ASIs), and epithelial sodium channel (ENaC) blockade target different levels of the aldosterone-related sodium-retention pathway in resistant hypertension (RH), but the comparative efficacy of individual agents remains uncertain. We conducted a focused drug-level network meta-analysis of randomized controlled trials (RCTs) comparing pathway-directed therapies in adults with RH. PubMed, Scopus, Embase, Cochrane CENTRAL, Cochrane Reviews, and ClinicalTrials.gov were searched from inception to July 20, 2026. The primary outcome was change in office systolic blood pressure (BP). Secondary outcomes included office diastolic BP and 24-hour ambulatory systolic and diastolic BP. Ten RCTs including 2865 participants were analyzed. In the primary drug-level analysis, amiloride, spironolactone, baxdrostat, eplerenone, and lorundrostat significantly reduced office systolic BP compared with placebo, with mean differences (MDs) of -14.08, -10.78, -9.09, -8.14, and -6.80 mmHg, respectively. Osilodrostat showed a statistically uncertain effect, with an MD of -2.61 mmHg. At the class level, both MRAs and ASIs showed clinically meaningful reductions in office systolic BP. Secondary outcomes were generally consistent with the primary analysis, although fewer trials contributed to these networks. Sensitivity analyses did not materially change the primary findings. These results support the aldosterone-related…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 2,865 participants or records.
Read the paper
Related studies
- Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis
- Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials
- Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials
- Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta‐analysis, and network meta‐analysis of randomized trials with 94,283 participants
- Screen time increases overweight and obesity risk among adolescents: a systematic review and dose-response meta-analysis
- Exposure to WHO AWaRe antibiotics and isolation of multi-drug resistant bacteria: a systematic review and meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.