Menaquinone-7 supplementation for 2 years significantly attenuated the progression of coronary artery calcification compared with placebo (P=0.02).
RCT (n=180)
Placebo-controlled
Randomized
Yes
p-value: p=.02
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 lt; .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
“CAC remains a powerful predictor of major cardiovascular events. Thus, before dismissing MK-7 as a form of treatment with a potentially adverse outcome, we need more information on the effects of this vitamin on hard endpoints.”
This study, published in JAMA Cardiology, suggests that Vitamin K2 (MK-7) supplementation may modestly attenuate the progression of coronary artery calcification in patients with existing CAD. This has generated significant interest in the preventive cardiology and nutrition communities as a potential non-statin intervention.
Vossen et al. (Wed,) conducted a rct in Symptomatic atherosclerotic coronary artery disease (CAD) (n=180). Menaquinone-7 (MK-7) vs. Placebo was evaluated on Evolution of the CAC score and calcium mass at 1 and 2 years of follow-up (p=.02). Menaquinone-7 supplementation for 2 years significantly attenuated the progression of coronary artery calcification compared with placebo (P=0.02).