Comparative Efficacy of Interventions for Vascular Calcification and Stiffness in Dialysis Patients: A Systematic...

Vascular calcification (VC) and vascular stiffness (VS) significantly increase cardiovascular risks in renal dialysis (RD) patients. Currently, several interventions have been tried to alleviate VC and VS, but they all lack systematic comparison. This study integrated randomized controlled trials (RCTs) of seven interventions to provide evidence-based insights to inform clinical decision-making.

A systematic search was conducted for all RCTs on drug treatments for VS or VC in patients receiving RD published between January 2001 and October 2025 in four databases: PubMed, Web of Science, Embase, and The Cochrane Library. Analyses were conducted in accordance with the PRISMA network meta-analysis (NMA) guidelines and registered in PROSPERO (CRD420251060534). Risk assessment was performed using the Cochrane Risk of Bias 2.0 tool. Bayesian NMA was then conducted using R software and Stata 15.0.

Sodium thiosulfate (STS) showed the highest Surface Under the Cumulative Ranking Curve (SUCRA) ranking for improving pulse wave velocity (PWV) (SUCRA = 89.4%), but no statistically significant difference was observed between STS and standard care (mean difference [MD] -1.3, 95% credible interval [95% CrI] -2.8, 0.2). No statistically significant differences were observed across all interventions for PWV improvement. Etidronic acid (EA) ranked first in SUCRA for reducing coronary artery calcification (CAC) volume score (SUCRA = 84.57%), but the difference versus most interventions did not reach statistical significance (MD -1,300, 95% CrI -3,800, 1,100). STS showed statistically significant reduction in CAC volume score compared with standard care, 300 mg SNF472, and 600 mg SNF472 (MD -188.27, 95% CrI -221.68, -154.52; MD -192.55, 95% CrI -245.83, -139.54; MD -182.39, 95% CrI -237.91, -126.55). For coronary artery and aortic Agatston scores, standard care showed superior SUCRA rankings, but EA exhibited a statistically significant difference compared with cinacalcet (aortic Agatston score: MD -1,175.11, 95% CrI -2,220.92, -125.45), indicating partial comparative efficacy among drugs.

This study suggests that SUCRA rankings indicate STS has a potential comprehensive advantage in improving VS and delaying calcification progression, making it a reasonable exploratory choice for dialysis patients with concurrent VC and VS. While EA ranks highest in SUCRA for reducing CAC volume score, it has limited impact on VS and requires caution regarding long-term safety. Given the limited sample size, network sparsity for some outcomes, and mostly non-significant between-group comparisons, large-scale, head-to-head RCTs are needed to further validate these findings.