Vitamin K2 and D3 Supplementation in Patients With Severe Coronary Artery Calcification: The DANCODE Trial.

BACKGROUND: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular events. We investigated whether supplementation with vitamin K2 and vitamin D3 reduces CAC progression in patients with severe coronary calcification. METHODS: In this multicenter, double-blind, placebo-controlled randomized trial, 400 participants with a CAC score ≥400 Agatston units (AU) were randomly assigned to vitamin K2 (720 μg/d) plus vitamin D3 (25 μg/d) or placebo for 24 months. Participants were enrolled from February 2023 to February 2024. Noncontrast cardiac computed tomography was performed at baseline, 12 months, and 24 months. The primary end point was change in CAC score at 24 months. Subgroup analyses by sex and baseline CAC subgroups (400-999 and ≥1000 AU) were performed. Change in plaque composition was assessed in a subset with CAC score <1000 AU who underwent coronary computed tomography angiography at baseline and 24 months. RESULTS: A total of 398 participants (30% women; median age, 71 years) were included. Median baseline CAC was 903 AU, and 44% had CAC ≥1000 AU. In the intention-to-treat analysis, the mean CAC increase was 196 AU (95% CI, 178-214) with vitamin K2 and D3 and 248 AU (95% CI, 225-271 AU) with placebo (between-group difference, -52 AU [95% CI, -79 to -24]). The treatment effect was consistent across sex and baseline CAC subgroups. In the 143 participants who underwent coronary computed tomography angiography, there were a similar increase in total plaque volume and no change in noncalcified plaque volume between groups; progression of calcified plaque volume was attenuated in the intervention group (between-group difference, -8 mm3 [95% CI, -13 to -2]). CONCLUSIONS: Among patients with severe CAC, supplementation with vitamin K2 and vitamin D3 reduced progression of CAC over 24 months. The reduction in calcification progression was not associated with an increase in noncalcified plaque volume. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05500443.