Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: The VitaVasK randomized controlled trial
Turgay Saritas, Sebastian Reinartz, Thilo Krüger, Markus Ketteler, Orfeas Liangos, Laura Labriola, Peter Stenvinkel, Christoph Kopp, Ralf Westenfeld, Pieter Evenepoel, Robert Siepmann, Stephanie Wied, R.-D Hilgers, Leon J. Schurgers, Jürgen Floege, for the VitaVasK Investigators
Abstract
Abstract Background Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Hemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicenter VitaVasK trial analyzed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CAC) and thoracic aortic calcifications (TAC). Methods Patients with preexisting CAC were randomized to continue on standard care or to additionally receive 5 mg vitamin K1 orally thrice weekly. Hierarchically ordered primary end points were progression of TAC and CAC in computed tomography scans at 18 months. Linear mixed effects models with repeated measures at baseline, 12 and 18 months assessed treatment effects after adjusting for study site. Results Of 60 randomized patients, 20 dropped out for reasons unrelated to vitamin K1, resulting in 23 control and 17 vitamin K1 patients. The trial was stopped early due to slow recruitment. At 18 months, the average TAC progression was 56% lower in the vitamin K1 compared to the control group (p = 0.039). CAC significantly progressed within the control group, but not within the vitamin K1 group. Average progression at 18 months was 68% lower in the vitamin K1 compared to the control group (p = 0.072). Vitamin K1 reduced plasma levels of pro-calcific uncarboxylated-MGP by 69% at 18 months. No treatment-related adverse events were noted. Conclusion Vitamin K1 intervention is a potent, safe and cost-effective approach to correct vitamin K deficiency and to potentially reduce cardiovascular calcification in this high-risk population.