Two Years of Menaquinone-7 Supplementation and Coronary Artery Calcification: A Randomized Clinical Trial

Abstract

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