Pharmacological interventions for vascular calcification in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials

Objective To evaluate the efficacy of pharmacological interventions for vascular calcification and related outcomes in patients with chronic kidney disease. Methods PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to 1 May 2026. Randomized controlled trials comparing pharmacological interventions with placebo, standard care, or other controls in patients with chronic kidney disease were included. Primary outcomes were imaging-defined measures of vascular calcification, including coronary artery calcification Agatston score, percentage coronary artery calcification progression, coronary artery calcification volume change, and abdominal aortic calcification progression. Secondary outcomes included carotid intima-media thickness, serum calcification propensity (T50), arterial stiffness, calcification-related biomarkers, mineral metabolism parameters, and all-cause mortality. Mean differences or odds ratios with 95% confidence intervals were pooled using fixed- or random-effects models according to heterogeneity. Results Twenty-eight randomized controlled trials involving 6330 participants were included. Pharmacological interventions did not significantly reduce the coronary artery calcification Agatston score, coronary artery calcification progression, coronary artery calcification volume change, abdominal aortic calcification progression, arterial stiffness, or all-cause mortality. Significant effects were observed for left carotid intima–media thickness (mean difference −0.06 mm, 95% confidence interval: −0.10 to −0.02), common carotid artery intima–media thickness (mean differences −0.07 mm, 95% confidence interval: −0.14 to −0.00), T50 change (mean differences 50.25 min, 95% confidence interval: 34.68–65.82), and dephosphorylated–uncarboxylated matrix Gla protein (mean differences −504.97 pmol/L, 95% confidence interval: −789.72 to −220.22). Most mineral metabolism parameters were unchanged, although ionized calcium was modestly reduced. Effects varied by pharmacological strategy, supporting intervention-specific interpretation. Conclusions Pharmacological interventions did not show consistent benefits on imaging-defined vascular calcification in patients with chronic kidney disease. Improvements in T50, dephosphorylated-uncarboxylated matrix Gla protein, and selected carotid intima–media thickness measures suggest pathway-specific biological or vascular effects that may precede or not directly translate into reduced structural calcification. Further randomized controlled trials with standardized imaging endpoints, longer follow-up, and clinically relevant subgroup reporting are needed to determine which therapeutic strategies provide meaningful vascular benefits.