rivaroxaban and Diabetic-Angiopathies

Activated factor X (FXa) plays a central role in the coagulation cascade, while it also mediates vascular function through activation of protease-activated receptors (PARs). Here, we examined whether inhibition of FXa by rivaroxaban, a direct FXa inhibitor, attenuates endothelial dysfunction in streptozotocin (STZ)-induced diabetic mice. Induction of diabetes increased the expression of a major FXa receptor, PAR2, in the aorta (P < 0.05). Administration of rivaroxaban (10 mg/kg/day) to diabetic wild-type (WT) mice for 3 weeks attenuated endothelial dysfunction as determined by acetylcholine-dependent vasodilation compared with the control (P < 0.001), without alteration of blood glucose level. Rivaroxaban promoted eNOS

Topics: Animals; Anthracenes; Aorta; Cell Line; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Endothelium, Vascular; Factor Xa; Factor Xa Inhibitors; Humans; JNK Mitogen-Activated Protein Kinases; Male; Mice; Mice, Knockout; Nitric Oxide Synthase Type III; Phosphorylation; Receptor, PAR-2; Rivaroxaban; Streptozocin; Vasodilation

To assess the effectiveness and safety of rivaroxaban vs warfarin in people with non-valvular atrial fibrillation and diabetes treated in routine practice.. Using US MarketScan claims data for the period November 2011 to December 2016, we identified oral anticoagulation-naïve people with non-valvular atrial fibrillation and diabetes (Type 1 or Type 2) and ≥12 months of continuous insurance coverage prior to the qualifying oral anticoagulation dispensing time. Rivaroxaban users were 1:1 propensity score-matched to warfarin users. Participants were followed until an event, oral anticoagulation switch/discontinuation, insurance disenrolment or end of follow-up. Rates (events/100 person-years) of the composite of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios and 95% CIs.. We assessed 5517 rivaroxaban users (20% received the reduced dose) and 5517 warfarin users with non-valvular atrial fibrillation and diabetes (~97% with Type 2 diabetes) with a median (interquartile range) available follow-up of 1.5 (0.7, 2.7) years. Rivaroxaban was associated with nonsignificant reductions in stroke or systemic embolism (0.87 vs 1.35/100 person-years; hazard ratio 0.68, 95% CI 0.44-1.05) and ischaemic stroke (0.69 vs 0.93/100 person-years; hazard ratio 0.78, 95% CI 0.48-1.30) compared with warfarin. No differences in major bleeding (2.7 vs 3.0/100 person-years; hazard ratio 0.96, 95% CI 0.74-1.25) were observed. Similar results were seen when analysis was limited to standard-dose rivaroxaban. Reduced-dose rivaroxaban was associated with a significantly decreased hazard of stroke or systemic embolism and ischaemic stroke, without an increase in major bleeding risk.. Rivaroxaban has effectiveness and safety at least as good as those of warfarin in people with diabetes and non-valvular atrial fibrillation treated in routine clinical practice.

Topics: Administrative Claims, Healthcare; Aged; Atrial Fibrillation; Databases, Factual; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Treatment Outcome; Warfarin

The present study estimates the effect of rivaroxaban on preventing deep vein thrombosis (DVT) in aged diabetics with femoral neck fractures after hip replacement. Our study consisted of 236 aged diabetics with femoral neck fractures, which were divided into the rivaroxaban and control groups. Reaction time (R time), clot formation time (K time), α angle (α), maximum amplitude (MA), clot elasticity (G) and coagulation index (CI), prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. DVT was diagnosed by color duplex Doppler ultrasound (CDDU). The risk factors of DVT were analysed by logistic regression analysis. Compared with the control group, in the rivaroxaban group, R time and K time were extended and α, MA and G decreased 1 day before operation. One day after operation, the rivaroxaban group had less PT and APPT and lower incidence of DVT than the control group. In the two groups, preoperative and postoperative PT and APPT significantly differed. Body mass index (BMI) ≥25, abnormal coagulation indicators, use of cemented femoral hip prosthesis, high haemoglobin content and non-ankle pump exercise after operation were the risk factors for DVT. Rivaroxaban could prevent DVT in aged diabetics with femoral neck fractures after hip replacement.

Topics: Aged; Arthroplasty, Replacement, Hip; Blood Coagulation; Body Mass Index; Diabetic Angiopathies; Female; Femoral Neck Fractures; Humans; Logistic Models; Male; Partial Thromboplastin Time; Postoperative Complications; Postoperative Period; Preoperative Period; Prothrombin Time; Reaction Time; Risk Factors; Rivaroxaban; Venous Thrombosis

Further to its pivotal role in haemostasis, factor Xa (FXa) promotes effects on the vascular wall. The purpose of the study was to evaluate if FXa modifies the expression level of energy metabolism and oxidative stress-related proteins in femoral arteries obtained from type 2 diabetic patients with end-stage vasculopathy.. Femoral arteries were obtained from 12 type 2 diabetic patients who underwent leg amputation. Segments from the femoral arteries were incubated in vitro alone and in the presence of 25 nmol l(-1) FXa and 25 nmol l(-1) FXa + 50 nmol l(-1) rivaroxaban.. In the femoral arteries, FXa increased triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase isotype 1 expression but decreased pyruvate dehydrogenase expression. These facts were accompanied by an increased content of acetyl-CoA. Aconitase activity was reduced in FXa-incubated femoral arteries as compared with control. Moreover, FXa increased the protein expression level of oxidative stress-related proteins which was accompanied by an increased malonyldialdehyde arterial content. The FXa inhibitor, rivaroxaban, failed to prevent the reduced expression of pyruvate dehydrogenase induced by FXa but reduced acetyl-CoA content and reverted the decreased aconitase activity observed with FXa alone. Rivaroxaban + FXa but not FXa alone increased the expression level of carnitine palmitoyltransferase I and II, two mitochondrial long chain fatty acid transporters. Rivaroxaban also prevented the increased expression of oxidative stress-related proteins induced by FXa alone.. In femoral isolated arteries from type 2 diabetic patients with end-stage vasculopathy, FXa promoted disruption of the aerobic mitochondrial metabolism. Rivaroxaban prevented such effects and even seemed to favour long chain fatty acid transport into mitochondria.

Topics: Acetyl Coenzyme A; Aged; Carnitine O-Palmitoyltransferase; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Energy Metabolism; Factor Xa; Female; Femoral Artery; Glycolysis; Humans; Male; Mitochondria; Morpholines; Oxidative Stress; Rivaroxaban; Thiophenes