rivaroxaban and Lupus-Erythematosus--Systemic

Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.. This randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily. Randomisation was done centrally, stratified by centre and patient type (with vs without systemic lupus erythematosus). The primary outcome was percentage change in endogenous thrombin potential (ETP) from randomisation to day 42, with non-inferiority set at less than 20% difference from warfarin in mean percentage change. Analysis was by modified intention to treat. Other thrombin generation parameters, thrombosis, and bleeding were also assessed. Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation. This trial is registered with the ISRCTN registry, number ISRCTN68222801.. Of 116 patients randomised between June 5, 2013, and Nov 11, 2014, 54 who received rivaroxaban and 56 who received warfarin were assessed. At day 42, ETP was higher in the rivaroxaban than in the warfarin group (geometric mean 1086 nmol/L per min, 95% CI 957-1233 vs 548, 484-621, treatment effect 2·0, 95% CI 1·7-2·4, p<0·0001). Peak thrombin generation was lower in the rivaroxaban group (56 nmol/L, 95% CI 47-66 vs 86 nmol/L, 72-102, treatment effect 0·6, 95% CI 0·5-0·8, p=0·0006). No thrombosis or major bleeding were seen. Serious adverse events occurred in four patients in each group.. ETP for rivaroxaban did not reach the non-inferiority threshold, but as there was no increase in thrombotic risk compared with standard-intensity warfarin, this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism.. Arthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.

Topics: Anticoagulants; Antiphospholipid Syndrome; Equivalence Trials as Topic; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prevalence; Rivaroxaban; Survival Rate; Thrombosis; Treatment Outcome; United Kingdom; Warfarin

The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS.. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin.. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed.. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5.

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Prospective Studies; Quality of Life; Recurrence; Rivaroxaban; Thrombin; Venous Thromboembolism; Warfarin

A 34-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted to our hospital for exacerbation of renal dysfunction, hemolytic anemia and thrombocytopenia. Twenty-two years before admission, she was diagnosed with SLE. Eight years before, lupus anticoagulant (LAC) positivity was detected without any thrombotic findings. Fourteen months before, renal function started to worsen. Three months before, unprovoked left leg swelling appeared. She was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Blood examination revealed mild anemia, thrombocytopenia, and renal dysfunction. Rivaroxaban was started after which the left leg swelling subsided. When she was referred to our hospital, LAC was positive, but hypocomplementemia nor elevation of serum anti-double-stranded DNA antibodies was detected. Renal biopsy showed acute and chronic thrombotic microangiopathy (TMA) without concurrent lupus nephritis. Brain magnetic resonance imaging showed new small multiple cerebral infarcts. Antiphospholipid antibody syndrome (APS), causing renal TMA, new cerebral infarction, and DVT was diagnosed. Rivaroxaban was changed to warfarin. Two months after admission, renal impairment improved, and the complete disappearance of DVT and brain infarcts was confirmed. This case suggests that warfarin may be more effective than direct oral anticoagulants in the treatment of APS-associated renal TMA.

Topics: Adult; Antiphospholipid Syndrome; Female; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Rivaroxaban; Thrombotic Microangiopathies; Treatment Outcome; Warfarin

Novel oral anticoagulant (NOAC) medications have revolutionized hematology and cardiology. Recently, NOACs have demonstrated additional promise in dermatology. Specifically, rivaroxaban, a direct factor Xa inhibitor NOAC, has been shown to be successful in the treatment of livedoid vasculopathy. Herein, we describe a patient with systemic lupus erythematosus who presented with painful cutaneous vasculopathy, demonstrated on biopsy with occlusive microvascular fibrin thrombi without evidence of concurrent vasculitis. Interestingly, imaging and laboratory studies did not show evidence of hypercoagulability, arterial disease, or embolic disease. The patient’s vasculopathy and pain progressed despite antiplatelet therapy, often considered first-line in cases of microvascular occlusive disease. However, with rivaroxaban therapy, the patient experienced complete regression of her painful lesions, thereby supporting a further role for NOACs in cutaneous vasculopathy treatment. J Drugs Dermatol. 2020;19(5) doi:10.36849/JDD.2020.4684.

Topics: Administration, Oral; Anticoagulants; Biopsy; Female; Foot; Humans; Lupus Erythematosus, Systemic; Middle Aged; Rivaroxaban; Skin; Skin Diseases, Vascular; Treatment Outcome

Topics: Antiphospholipid Syndrome; Factor Xa Inhibitors; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

To examine the effects of patients taking the direct blood coagulation factor Xa inhibitor rivaroxaban on lupus anticoagulant testing results in a clinical setting.. We reviewed the results of lupus anticoagulant testing performed over a 2-year period. Of 59 patients who met criteria for a lupus anticoagulant, 18 were taking rivaroxaban. We reviewed and compared the parameters of lupus anticoagulant testing.. The average dilute Russell viper venom time (DRVVT) and normal plasma-mix screening results to confirmation ratios in rivaroxaban-naïve patients were 1.6 and 1.7, respectively. In the rivaroxaban group, the same parameters were 1.7 and 1.6, respectively (P = - 0.28 and 0.46, respectively). For 15 of 18 patients taking rivaroxaban, results were corrected on the confirmation steps of both tests.. Rivaroxaban confounds lupus anticoagulant testing because the DRVVT is prolonged in these patients but it also corrects with excess phospholipid, mimicking a lupus anticoagulant. Patient medication review is critical to avoid false-positive findings and inappropriate diagnosis of antiphospholipid syndrome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Factor Xa Inhibitors; False Positive Reactions; Female; Humans; Immunologic Factors; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Mass Screening; Middle Aged; Phospholipids; Rivaroxaban

Topics: Antiphospholipid Syndrome; Humans; Lupus Erythematosus, Systemic; Rivaroxaban; Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Pregnancy; Pregnancy Complications; Rivaroxaban; Secondary Prevention; Venous Thromboembolism; Warfarin; Young Adult

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Drug Substitution; Female; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Recurrence; Retrospective Studies; Rivaroxaban; Splenic Vein; Stroke; Thiophenes; Thromboembolism; Thrombophilia; Treatment Failure; Venous Thrombosis; Warfarin