Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification

Importance Vitamin K supplementation can reduce progression of vascular calcification in patients with diabetes or end-stage kidney disease. Presently, it is unknown whether vitamin K is also beneficial in patients with symptomatic atherosclerotic coronary artery disease (CAD). Objective To evaluate whether supplementation with the vitamin K homologue menaquinone-7 (MK-7) for a period of 2 years attenuates the progression of coronary artery calcification (CAC) compared with placebo. Design, Setting, and Participants This randomized placebo-controlled clinical trial including symptomatic patients with CAC score between 50 and 400 Agatston units (AU) with 2 years of follow-up (VitaK-CAC study). The study was conducted at 1 university hospital and 1 community-dwelling hospital in the Netherlands. Data were collected from January 2012 through October 2022 with a few interruptions; analyses were performed from January 2023 to April 2024. Intervention Supplementation with either the vitamin K homologue menaquinone-7 (MK-7) in a daily dose of 360 µg or identical placebo. Main Outcomes and Measures The primary outcome of the study was the evolution of the CAC score and calcium mass at 1 and 2 years of follow-up, as measured with computed tomography (CT) scanning. Additionally, CT angiography was performed. The incidence of new calcifications was a secondary outcome measure. Data were analyzed using a generalized estimation equations model, adjusted for covariates. Results Altogether, 180 patients could be randomized (90 patients per group), with 85 patients receiving MK-7 (median [IQR] age, 59 [54-65] years; 36 [42%] female) and 82 receiving placebo (median [IQR] age, 61 [54-65] years; 34 [42%] female). Baseline characteristics were comparable for the 2 groups. Plasma levels of MK-7 rose significantly in the active treatment group (median [IQR], 0.50 [0.32-0.77] µg/L to 6.56 [2.04-10.35] µg/L; P < .001). In the placebo group, CAC scores increased from a median (IQR) of 145 (99-217) AU to 173 (119-297) AU after the first year and to 214 (148-344) AU after the second. In the active treatment group, these values were 135 (89-226), 150 (110-254) and 184 (122-298) AU, respectively. The difference between the groups was significant ( P = .02), even after adjustment for covariates. A similar result was seen for calcium mass. The increase in CAC score correlated with the number of noncalcified plaques that became partially calcified during the study ( R 2 = 0.17; P = .04). No significant adverse effects were observed. Conclusions and Relevance The findings of this study suggest that supplementation with MK-7 for 2 years may slow calcification in noncalcified plaques of patients with symptomatic CAD. The clinical significance of this finding in terms of plaque stability remains to be determined. Trial Registration ClinicalTrials.gov Identifier: NCT01002157