rivaroxaban and Vasculitis

Cutaneous small vessel vasculitis (CSVV) was identified as a safety signal among patients treated with direct oral anticoagulants (DOAC). This study aimed to determine if CSVV risk differed among patients with atrial fibrillation (Afib) who newly initiated warfarin or a DOAC.. We identified enrollees aged ≥21 years diagnosed with Afib who newly initiated rivaroxaban, dabigatran, apixaban, and warfarin in the Sentinel Distributed Database from October 19, 2010 to February 29, 2020. We selected and followed patients who did not have evidence of the following in the 183 days prior to initiating treatment: CSVV diagnosis, dispensing of other study drugs, select autoimmune diseases or autoimmune medications, cancer diagnoses or chemotherapeutic treatment, kidney dialysis or transplant, alternative anticoagulation indications, or an institutional (nursing home, hospice, hospital) stay on the treatment initiation date (index date) until CSVV outcome or pre-specified censoring. We conducted 1:1 propensity score matching in six comparisons.. CSVV incidence rates for DOACs and warfarin ranged from 3.3 to 5.6 per 10 000-person years in our matched Afib population. The adjusted CSVV hazard ratio (HR) and 95% confidence interval (CI) was 0.94 (0.64, 1.39) for rivaroxaban versus warfarin; 1.17 (0.67, 2.06) for dabigatran vs. warfarin; 0.85 (0.62, 1.16) for apixaban vs. warfarin; 0.86 (0.49, 1.50) for rivaroxaban vs. dabigatran; 0.99 (0.68, 1.45) for rivaroxaban versus apixaban; and 1.70 (0.90, 3.21) for dabigatran versus apixaban.. We did not find significant evidence of differential CSVV risk in pair-wise comparisons of DOACs and warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Humans; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Vasculitis; Warfarin

Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study was to investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute vascular inflammatory response. Male rats were treated with 5 mg/kg RVX (oral gavage) followed by 10 mg/kg LPS i.p injection. Circulating levels of IL-6, MCP-1, VCAM-1, and ICAM-1 were measured in plasma 6 and 24 hours after LPS injection, while isolated aorta was used for gene expression analysis, immunohistochemistry, and vascular tone evaluation. RVX pre-treatment significantly reduced LPS mediated increase after 6h and 24h for IL-6 (4.4±2.2 and 2.8±1.7 fold), MCP-1 (1.4±1.5 and 1.3±1.4 fold) VCAM-1 (1.8±2.0 and 1.7±2.1 fold). A similar trend was observed in the aorta for iNOS (5.5±3.3 and 3.3±1.9 folds reduction, P<0.01 and P<0.001, respectively), VCAM-1 (1.3±1.2 and 1.4±1.3 fold reduction, P<0.05), and MCP-1 (3.9±2.2 and 1.9±1.6 fold reduction, P<0.01). Moreover, RVX pre-treatment, improved LPS-induced PE contractile dysfunction in aortic rings (Control vs LPS, Emax reduction = 35.4 and 31.19%, P<0.001; Control vs LPS+RVX, Emax reduction = 10.83 and 11.48%, P>0.05, respectively), resulting in 24.5% and 19.7% change in maximal constriction in LPS and LPS+RVX respectively. These data indicate that RVX pre-treatment attenuates LPS-induced acute vascular inflammation and contractile dysfunction.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Aorta; Disease Models, Animal; Endothelium, Vascular; Humans; Lipopolysaccharides; Male; Rats; Rivaroxaban; Vasculitis; Vasoconstriction

Anticoagulants have recently been recognised as a cause of acute kidney injury (AKI). We describe the case of a 75-year-old man with IgA vasculitis and atrial fibrillation treated with rivaroxaban, who presented with macroscopic haematuria and an acute decline in renal function. Two months before referral, he noted palpable purpuric lesions and was diagnosed with IgA vasculitis based on skin biopsy findings; the skin lesion disappeared following treatment with a steroid external preparation. Renal biopsy revealed glomerular haemorrhage and red blood cell casts. Although rivaroxaban was withdrawn, his kidney function worsened and he was started on haemodialysis. His renal function did not recover. To the best of our knowledge, this is the first case of direct oral anticoagulant (DOAC)-related AKI in systemic vasculitis. During DOAC therapy, close monitoring of a patient's urinalysis results and their renal function may be required for patients with systemic vasculitis to avoid AKI.

Topics: Acute Kidney Injury; Aged; Diagnosis, Differential; Factor Xa Inhibitors; Humans; Immunoglobulin A; Male; Renal Dialysis; Rivaroxaban; Vasculitis