Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: the VitaVasK randomized controlled trial

Abstract

Background: Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Haemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicentre VitaVasK trial analysed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CACs) and thoracic aortic calcifications (TACs).

Methods: Patients with pre-existing CACs were randomized to continue on standard care or to additionally receive 5 mg of vitamin K1 orally thrice weekly. Hierarchically ordered primary endpoints were progression of TAC and CAC in computed tomography scans at 18 months. Linear mixed effects models with repeated measures at baseline and 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 with the control group (p = .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 = .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.

Keywords: matrix Gla protein; valvular calcification; vascular calcification; vitamin K.

Graphical Abstract

Figure 1:

Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

Figure 2:

Primary endpoints of the VitaVasK trial: (A) progression of TAC (i.e. the absolute change of the volume score at the 12- and 18-month MSCT versus the baseline MSCT) as well as (B) progression of CAC (i.e. the absolute change in the volume score at the 12- and 18-month MSCT versus the baseline MSCT). Individual data, means and SDs are shown.

Figure 3:

Secondary endpoints of the VitaVasK trial: (A) progression of TAC (i.e. the absolute change in the Agatston score at the 12- and 18-month MSCT versus the baseline MSCT), (B) progression of CAC (i.e. the absolute change in the Agatston score at the 12- and 18-month MSCT versus the baseline MSCT), (C) progression of aortic valve calcification (i.e. the absolute change in the volume score at the 12- and 18-month MSCT versus the baseline MSCT) and (D) progression of mitral valve calcification (i.e. the absolute change in the volume score at the 12- and 18-month MSCT versus the baseline MSCT). Individual data, means and SDs are shown.

Figure 4:

Biochemical endpoints of the VitaVasK trial: (A) change in serum vitamin K1 concentration versus baseline at follow-up visits of 4 weeks, 12 months and 18 months and (B) change in plasma ucMGP concentration versus baseline at follow-up visits of 4 weeks, 12 months and 18 months. Individual data, means and SDs are shown.