MENAQUINONE-7 SLOWS DOWN PROGRESSION OF CORONARY ARTERY CALCIFICATION. A RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Objective: Although several studies have shown that vitamin K supplementation can slow down the progression of vascular calcification, studies in humans are restricted to high-risk patients such as those with diabetes or end-stage renal disease. The present study aimed to explore whether vitamin K supplementation can also retard such progression in patients with only mild to moderate coronary artery disease and no other abnormalities other than hypertension. Design and method: We performed a double-blind, placebo-controlled, randomized trial in which patients of either sex with mild to moderate coronary artery calcification were randomized to treatment with either the vitamin K2 homologue MK-7 or placebo. We performed CT scanning to assess the evolution, relative to baseline, of coronary artery calcification at 1 and 2 years of follow-up. In addition, we assessed vitamin K status based on serum levels of vitamin K 1 and K2 and of levels of dephosphorylated, uncarboxylated matrix Gla-protein. The primary outcome was analysed in an unadjusted and adjusted general estimation equations (GEE) model. Results: In the intention-to-treat analysis, 180 patients were included (90 per group). In both groups, K1 levels remained unchanged. MK-7 levels rose significantly in the active treatment group (p<0.001) but not in the placebo group. Levels of dp-ucMGP rose in both groups although significantly less in the treated group (p<0.001). Levels of dp-ucMGP rose in both groups although significantly less in the treated group (p<0.001). Although progression of calcification continued in both groups, MK-7 was able to significantly lower the rate of progression, both in unadjusted and adjusted analyses (unadjusted coefficient 29 Agatston units/year [95%CI 2-57], p=0.04, adjusted coefficient 18 Agatston units/year [95%CI 2-34], p=0.03). These findings were consistent for both absolute and relative changes in calcification score. MK-7 had no effect on blood pressure and the effects of MK-7 were comparable in normotensives and hypertensives. No significant adverse effects were observed.Conclusions: This study shows that a two-year period of supplementation with MK-7 can slow down the progression of coronary artery calcification in patients with mild to moderate coronary artery disease, irrespective of blood pressure status.