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. 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.

Cardiovascular Calcification Heterogeneity in Chronic Kidney Disease

“…Recent results from a randomized prospective clinical study demonstrated 56% lower thoracic aortic calcification and 68% lower CAC in hemodialysis patients treated with 5 mg vitamin K1 3× per week compared with patients only receiving standard care. 177 Trending differences in valvular calcification were also observed but did not reach statistical significance. The observed differences in calcification associated with significantly lower plasma levels of dephosphorylated uncarboxylated form of MGP, with the vitamin K1–treated group exhibiting only 36% of this inactive form compared with the untreated patients after 4 weeks and persisted to the reported end point at 18 months.…”

“…Only 40 patients were included in the final end point analyses of the study. 177 Of note, supplementation of vitamin K2 in the form of MK-7 (menaquinone-7) in patients with CKD failed to show any beneficial cardiovascular effects (like calcification progression, pulse wave velocity, or cardiovascular events), 178,179 explained by a disturbed lipoprotein-mediated MK-7 transport in patients with CKD. 180 Future studies will need to more fully examine whether decreased calcification proves beneficial in reducing cardiovascular events across the wide spectrum of patients with CKD.…”

The Pleiotropic Role of Vitamin K in Multimorbidity of Chronic Obstructive Pulmonary Disease

“…Therefore, vitamin K1 may be more effective in CKD. Indeed, a recent trial in hemodialysis patients with pre-existing CAC demonstrated that high dose vitamin K1 supplementation for the duration of 18 months resulted in a significant deceleration of thoracic aortic calcium (TAC) progression and a trend towards an attenuation of CAC progression [ 85 ]. Other trials of vitamin K1 supplementation in the CKD population are currently ongoing [ 84 ].…”

Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies

“…125 As underpowered clinical randomized Vitamin K trials have shown divergent results, fully powered randomized trials should be initiated possibly combining vitamin K2 with a phosphate binder. [126][127][128][129] Mitochondrial Dysfunction-When Cells Run Out of Energy…”