menaquinone-6 and Atrial-Fibrillation

In patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown.. In the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2-3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding.. Median (IQR) follow-up was 1.88 (1.01-3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk-adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68;. In patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA.. Oral Anticoagulation in Hemodialysis, NCT03799822.

Topics: Aged; Aged, 80 and over; Antifibrinolytic Agents; Atrial Fibrillation; Cardiovascular Diseases; Factor Xa Inhibitors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Mortality; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Vitamin K; Vitamin K 2

Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation.. Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000. Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm.. Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.

Topics: Aged; Aged, 80 and over; Antifibrinolytic Agents; Atrial Fibrillation; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Humans; Male; Prospective Studies; Renal Dialysis; Rivaroxaban; Stroke; Vascular Calcification; Vitamin K; Vitamin K 2; Vitamin K Deficiency

Vitamin K is an essential factor for synthesis of plasma clotting proteins and for site-specific carboxylation of bone Gla protein and other bone matrix proteins. Low vitamin K has been associated with reduced bone mineral density. Warfarin therapy, which inhibits vitamin K-dependent blood-clotting, has been demonstrated to reduce the risk of stroke in nonrheumatic atrial fibrillation. We evaluated vitamin K and bone mineral density in nonrheumatic atrial fibrillation patients who had long-term warfarin therapy after an ischemic stroke.. Sera were collected from 64 patients with non-rheumatic atrial fibrillation and ischemic stroke who had been treated with warfarin, 63 stroke patients without warfarin, and 39 control subjects. All stroke patients in both groups had hemiplegia. Sera were assayed for vitamins K1 and K2, bone Gla protein, and 25-hydroxyvitamin D. Bone mineral density was determined in both second metacarpals.. Serum vitamin K1 concentrations (ng/mL) were lower in treated patients (.234 +/- .177 ng/mL) than in untreated patients (.329 +/- .284) or controls (.553 +/- .164). Bone Gla protein was lower in treated patients' sera (1.241 +/- .799 ng/mL) than in untreated patients (4.476 +/- 3.226). Concentrations of 25-hydroxyvitamin D were lower in both patient groups. Bone mineral density was lower on both sides in treated patients than in untreated patients (P < .0001). Vitamin K1 and bone Gla protein were significantly related to bone mineral density bilaterally in treated but not in untreated patients.. Bone mineral density was significantly lower in stroke patients with long-term warfarin treatment than in untreated patients. Both warfarin-induced reduction in vitamin K function and lowered vitamin K1 concentrations are probable causes of this osteopenia.

Topics: Administration, Oral; Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Bone Density; Cerebral Infarction; Female; Humans; Male; Middle Aged; Regression Analysis; Vitamin K; Vitamin K 1; Vitamin K 2