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 (R2 = 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.