Menaquinone-7 (MK-7), commonly known as vitamin K2, is a cofactor for the carboxylation of proteins involved in arterial calcification inhibition and has been shown to slow the course of aortic valve calcification (AVC) in individuals with aortic stenosis. Men from the community with an AVC score of >300 arbitrary units (AU) on cardiac non-contrast computed tomography were assigned to daily therapy with tablet 720 µg MK-7 + 25 g vitamin D or matched placebo for 24 months in a randomized, double-blind, multicenter experiment. The change in AVC score was the primary result. Changes in the aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, aortic and coronary artery calcification, and dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein) were among the secondary outcomes.] All-cause mortality and cardiovascular events were among the safety outcomes.

About 365 males were randomly assigned between February 1, 2018, and March 21, 2019. The average age was 71.0 (4.4) years. In the intervention and placebo groups, the mean (95% CI) rise in AVC score was 275 AU (95% CI, 225–326 AU) and 292 AU (95% CI, 246–338 AU), respectively. The mean difference in AVC progression was 17 AU (95% CI, –86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, –0.09 to 0.12 cm2; P=0.78), and the mean change in peak aortic jet velocity was 0.04 m/s (95% CI, –0.11 to 0.02 m/s; P=0.21). The evolution of aortic and coronary artery calcification scores was not substantially different between MK-7 plus vitamin D patients and placebo patients. There was no difference in heart valve surgery (1 against 2 patients; P=0.99), all-cause mortality (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). MK-7 + vitamin D resulted in a substantial decrease in dp-ucMGP compared to the placebo arm (–212 pmol/L vs. 45 pmol/L; P<0.001). MK-7 with vitamin D administration for two years had no effect on AVC advancement in older men with AVC scores greater than 300 AU.