Comparative Efficacy of Treatments for Resistant or Uncontrolled Hypertension: A Network Meta-Analysis of Randomized Trials
In brief
Spironolactone lowers office blood pressure by about 12 mm Hg in resistant hypertension
In a network meta-analysis of randomized trials, spironolactone lowered office systolic blood pressure by about 12 mm Hg versus baseline treatment in resistant hypertension; radiofrequency renal denervation lowered it by about 9 mm Hg. Similar findings appeared in broader uncontrolled hypertension, but head-to-head comparisons did not establish that any add-on treatment was clearly better than another.
- Journal
- JACC. Advances (Q1)
- Published
- 5 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Angelo Laino, Raffaele Piccolo, Antonio Pio Vitale, Raffaele Izzo, Anna Franzone, Giovanni Esposito
- PMID
- 42832922
- DOI
- 10.1016/j.jacadv.2026.103306
Why clinicians should know about it
- Picked for Nephrology (top studies of the week, 11 October 2026): Network meta‑analysis of resistant hypertension
Abstract
BACKGROUND: Many patients with hypertension fail to achieve recommended blood pressure targets despite treatment with 2 or more antihypertensive drugs. OBJECTIVES: We aimed to compare the efficacy of add-on treatments for the management of resistant or uncontrolled hypertension. METHODS: We searched Embase and MEDLINE through November 2025. We included randomized trials comparing add-on treatments for resistant or uncontrolled hypertension. The certainty of evidence was assessed using the Confidence In Network Meta-Analysis (CINeMA) framework. The primary outcome was the change in office systolic blood pressure from baseline. Summary mean differences were estimated using random-effects network meta-analysis within a Bayesian framework in patients with resistant hypertension and in the broader population with uncontrolled hypertension. RESULTS: We included 35 trials (8,648 patients and 12 individual treatments) in the systematic review and 30 trials (8,187 patients and 10 individual treatments) in the network meta-analysis. In patients with resistant hypertension, spironolactone (mean difference: -12.43 mm Hg; 95% credible interval: -17.68 to -7.18; CINeMA moderate) and radiofrequency renal denervation (mean difference: -8.74 mm Hg; 95% credible interval: -12.96 to -4.52; CINeMA moderate) were more effective than baseline treatment in reducing office systolic blood pressure. Similar findings were observed in patients with uncontrolled hypertension. No intervention demonstrated clear superiority over another because most head-to-head comparisons included the possibility of no effect. CONCLUSIONS: In head-to-head comparisons, no significant differences were observed between add-on treatments in reducing blood pressure among patients with resistant or uncontrolled hypertension. Treatment selection should prioritize treatments with demonstrated superiority over baseline treatment, including spironolactone, baxdrostat, and radiofrequency renal denervation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.