Safety Of Oral Rivaroxaban Research Articles

Use of oral rivaroxaban in cerebral venous thrombosis

Background Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in humans and the mainstay of treatment is anticoagulation unless contraindicated. Non-vitamin K oral anticoagulants have not been duly evaluated in randomized controlled trials in CVT. Objective To compare the efficacy and safety of oral rivaroxaban with vitamin K anticoagulant (warfarin) in preventing recurrent venous thromboembolism (VTE) in patients with CVT. Methods Adult patients with CVT, who were stable after 5–12 days of treatment with parenteral heparin 1 mg/kg, were screened for eligibility. The patients were randomly divided into two groups to receive oral rivaroxaban 20–30 mg daily or warfarin 1, 3 or 5 mg daily (with the dose adjusted to maintain an INR of 2–3), for 3–12 months. Recanalization rates, periprocedural complications, and clinical outcomes were assessed by Magnetic Resonance Venography (MRV) and National Institutes of Health Stroke Scale (NIHSS) at 3rd, 6th and 12th month follow-ups. Results In total, 45 patients with CVT were randomized to the two treatment groups (21 to rivaroxaban and 24 to warfarin). Overall recanalization was achieved by 18 (86%) and 20 (83%) cases from rivaroxaban and warfarin group, respectively at 6th month follow-up; and by all 45 (100%) cases from the both groups at 12th month follow-up. Excellent outcome (NIHSS score 0) was obtained by 20 (95%) cases from rivaroxaban group at 3rd to 12th month follow-ups; and by 23 (96%) cases at 6th to 12th month follow-ups. There were no major bleeding events during the trial. None of the patients developed recurrence of thrombosis. Statistically, no significant difference between the two treatment groups in terms of recanalization and clinical outcomes could be observed. Conclusion Rivaroxaban is a safe option in CVT however; larger randomized controlled studies will impact the results validity.

Incidence of DVT in post-operative lower limb trauma patients and the role of rivaroxaban in prevention of DVT

Background: Deep vein thrombosis (DVT) is a common cause of morbidity and mortality after Orthopedic surgery. Some recent studies report an increasing incidence of VTE in the Indian subcontinent. Rivaroxaban was found to be safe and effective for thromboprophylaxis after major Orthopedic surgery across a wide range of doses. Aim: To study incidence of DVT in lower limb trauma patients and the efficacy and safety of oral rivaroxaban, 10 mg once daily, administered postoperatively, for the prevention of venous thromboembolism.Material and Methods: A total of 200 patients selected by simple random sampling with lower limb trauma admitted for surgery in the hospital were included in the study. The patients were randomized into two groups of 100 patients each. RE was given oral Rivaroxaban, 10 mg once daily for the prevention of venous thromboembolism and Group E, control group, for which no prophylaxis was given. Results: Incidence of DVT was 3% in Group RE and 6% in group E. There was statistical significant difference when two groups were compared statistically. Incidence was 7% in males and 2% in females. The mean duration of treatment in patients in Group RE was 26.32± 13.21 days and in Group E was 16.32 ±4.21 days. The adverse event of bleeding in patients of Group RE was 3% and in Group E was 2% with no statistically difference. Conclusion: DVT in Indian patients with lower limb trauma is a fair problem and hence pharmacological prophylaxis should be used only for all patients with risk factors. Rivaroxaban offers a simple, approach to the short-term treatment of DVT that may improve the benefit-risk profile of anticoagulation.

Comparing Prophylactic Effect of Rivaroxaban and Enoxaparin on Thromboembolism After Total Hip or Knee Arthroplasty

Background: Vascular thromboembolism is one of the major concerns of orthopedic surgeons after hip or knee replacement surgery. Although many thromboprophylactic drugs have been introduced, there is still no consensus over their efficacy and safety. Therefore, this study aimed to compare the efficacy and safety of oral rivaroxaban and aspirin administration and enoxaparin injections in patients undergoing knee or hip replacement. Objectives: Determination and comparison of the side effect and efficacy of Rivaroxaban and Enoxaparin after total hip or knee arthroplasty. Methods: A total of 231 patients undergoing knee or hip replacement surgery were included in the study. Of them, 31 patients were excluded due to missing the follow-up. Of the remaining 200 patients, 42 low-risk and 158 moderate- to high-risk patients were identified, according to Caprini risk assessment model. Then, they were divided into three groups: aspirin (42 patients), enoxaparin (78 patients), and rivaroxaban (80 patients). Severe hemorrhage (hemoglobin reduction of more than 2 g/dL or requiring blood transfusion) was assessed after the first dose of medication until discharge through daily hemoglobin testing. Frequency of other side effects such as wound complications (ecchymosis, hematoma, and wound infection) and gastrointestinal or skin problems was recorded and compared by daily examination during the hospital stay and then in the future visits to the clinic up to 6 months in each group. Follow up visits were performed at weeks 6, 12, and 24. Results: No cases of deep vein thrombosis or pulmonary thromboembolism were observed in any of the study groups. There was no significant difference between the two groups in the number of major bleeding cases (P=0.39). Ecchymosis around the wound was significantly higher in the rivaroxaban group than in the enoxaparin group (33.8% vs. 23%). However, this difference was not statistically significant (P=0.06). Conclusion: The efficacy and safety of rivaroxaban and enoxaparin drugs are comparable. Although ecchymosis was seen after using rivaroxaban rather than enoxaparin, rivaroxaban is orally administered and costs less for the patient and the health system. So, its use as a thromboprophylactic drug of choice following hip and knee arthroplasty surgery is still recommended.

Conservative Treatment of Upper Extremity Deep Vein Thrombosis with Oral Rivaroxaban: A Single-center Experience

Introduction -The aim of the study was to assess efficacy and safety of oral Rivaroxaban in the treatment of upper extremity deep vein thrombosis (UEDVT). Methods - This was a prospective observational study involving patients with the first episode of UEDVT confirmed by duplex ultrasound (DUS) without symptoms of pulmonary embolism (PE). All patients initially received low-molecular-weight heparins for 1-2 days and then were switched to oral rivaroxaban 15 mg bid for 3 weeks and then 20 mg qd up to three months. Those after interventional treatment of UEDVT were excluded. Patients were followed up with clinical examination and DUS for 6 months. The endpoints of the study were: symptomatic PE, recurrent UEDVT, major, clinically relevant non-major and minor bleeding, recanalization of the affected veins, recognized as any blood flow with DUS, the incidence of postthrombotic syndrome (PTS) of the affected limb assessed by modified Villata score by Czihal (1). Results - Totally 30 patients (13 men and 17 women) aged 28-78 years (mean age 52.4 ± 17.3) were included in the study. 16.7% of them had physical effort as a trigger factor for UEDVT. In 13.3% there was a pacemaker previously implanted through the affected limb. Also, patients had from 0 to 5 individual risk factors for venous thromboembolism (mean - 1.9±1.6). The subclavian vein was involved in the thrombotic process in all cases, predominantly on the right side (60%). The mean duration of symptoms before diagnosis was 1.8±1.7 days. All of 30 patients were followed up for 6 months. There were no episodes of symptomatic PE and/or recurrent UEDVT during the period of anticoagulation (0-3 months) and after stop of treatment (3-6 months). No episodes of major bleeding were observed. Clinically relevant non-major bleeding occurred in 2 patients (6.7%: 95% CI: 1.9-21.4%) represented by uterine bleeding and large skin hemorrhage. Minor bleeding was observed in 2 patients (6.7%: 95% CI: 1.9-21.4%) represented by nasal and gingival bleeding. So cumulative incidence of bleeding was 13.4% (95% CI: 5.4-29.8%). Recanalization of upper extremity deep veins was observed at all affected limbs at 3 months and persist up to 6 months. The signs of upper limbs PTS (5 and more modified Villalta score) were found in 4 patients (13.4 %; 95% CI: 5.4-29.8%) and the mean score was 2.1±1.9. Conclusion - Treatment of UEDVT with oral rivaroxaban seems to be effective, safe and associated with the low incidence of upper limb PTS.

The Efficacy and Safety of Oral Rivaroxaban in Patients with Non-Valvular Atrial Fibrillation Scheduled for Electrical Cardioversion.

Objective Electrical cardioversion (EC) is associated with an increased risk of thrombotic events in patients with non-valvular atrial fibrillation (NVAF). Patients who experience AF for a period of >48 hours therefore require adequate anticoagulation therapy for at least 3 weeks before and 4 weeks after EC. While the guidelines address the management of vitamin K antagonists (VKAs), there are limited data on the use of novel oral anticoagulants (NOAC). One NOAC, rivaroxaban, has a rapid onset of action and might therefore shorten the time for which anti-coagulant treatment is required before a patient undergoes EC. Methods This study included 91 patients with NVAF of >48 hours in duration or in whom the time of onset was unknown who were undergoing EC after pretreatment with rivaroxaban. All of the patients were pretreated with rivaroxaban for at least 2 hours before EC and the same dose of rivaroxaban was prescribed for 4 weeks after EC. The primary endpoint was a successful EC without any thrombotic events or bleeding complications within 30 days after EC. The secondary endpoint was the time to EC. Results The mean age was 63±12 years and 70 of the 91 patients were male. The CHADS2 and HAS-BLED scores were 1.0±1.0 and 1.7±1.3, respectively. Although there were no thrombotic events, minor bleeding (gingival hemorrhage) occurred 20 days after the initiation of rivaroxaban treatment in one patient. The average time to EC was 11.9±11.1 days. Conclusion Rivaroxaban is safe and effective drug for NVAF patients who are scheduled for an EC. Furthermore, since VKAs take a substantial amount of time to establish adequate anticoagulation, pretreatment with rivaroxaban could shorten the time to the EC.

The Efficacy and Safety of Oral Rivaroxaban in Patients with Permanent Inferior Vena Cava Filter: A Pilot Case-Control Study

Aim: to evaluate the efficacy and safety of direct oral anticoagulant Rivaroxaban in patients with permanent Inferior Vena Cava (IVC) filter.Methods. This was a prospective case-control study involving 30 patients with acute DVT after implantation of IVC filter. The indication for temporary IVC filter implantation was proximal deep vein thrombosis (DVT) with ≥ 4 cm free-floating head. In the study were included patients in whom IVC filter was not removed 3 weeks after implantation because of technical failure (66.7%), persistence of irreversible risk factors or free-floating head (23.3% and 10%). After IVC filter implantation all patients were initially treated with low molecular weight heparins for 48 hours and then assigned to a standard anti-vitamin K therapy (AVK). Those who refused standard anticoagulation were allowed to choose a new oral anticoagulant and some of them were treated with Rivaroxaban 15 mg twice daily for the first 3 weeks, followed by 20 mg once daily. Totally 15 patients were treated with oral Rivaroxaban on their own: 8 men and 7 women, 35-87 years old (mean - 65.6±15.2) with 1-6 individual risk factors for venous thromboembolism (mean - 2.9±1.4). For each case patient the control one treated with AVK was matched by age (±5 years), sex and the number of individual risk factors (±1). Matching was successful in 100%.Patients were evaluated at 6th, 12th, 18th and 24th month after intervention with clinical examination, duplex ultrasound of IVC system and inspection of medical records. The endpoints of the study were: the patency of IVC filter, the rates of recurrent DVT, pulmonary embolism (PE) and bleeding.Results. During 12 month we followed up all 30 patients, during 18 month we followed up 9 cases and 14 controls and during 24 month - 2 cases and 6 controls. We found no IVC filter obstruction or PE in all patients treated with Rivaroxaban or AVK during the whole time of observation. At 6th month after intervention, we found no recurrent DVT. Hemorrhagic complications were found in one case and two controls (6.6% vs 13.3%, n.s.). At 12th month after intervention, we found one recurrent DVT in control patient (0% vs 6.6%, n.s.). New hemorrhagic complications were found in one case and one control. Totally hemorrhagic complications during first year of observation were found in 2 patients at Rivaroxaban and 3 patients at AVK without any statistically significant difference (13.3% vs 20.0%), but in controls they were more severe: one intracranial hemorrhage and two skin hemorrhage versus one skin and one gingival hemorrhage. During the second year of observation we found no new cases of DVT or bleeding.Conclusion. Using of oral Rivaroxaban in patients with permanent IVC filter seems to be not less effective and safe as standard therapy with AVK and does not lead to filter obstruction. These findings need to be confirmed in a randomized controlled trial. DisclosuresLobastov:HemaCore Company: Honoraria, Other: travel funding, Research Funding; Bayer: Honoraria, Other: travel funding. Off Label Use: Prolonged treatment of DVT with Rivaroxaban in patients with permanent inferior vena cava filter. Schastlivtsev:Bayer: Honoraria, Other: travel finding. Barinov:Bayer: Honoraria, Other: travel funding.

Oral Rivaroxaban Versus Standard Therapy for the Treatment of Symptomatic Venous Thromboembolism in Patients with Cancer

ABSTRACT Objective: To compare the efficacy and safety of oral rivaroxaban with that of enoxaparin/vitamin K antagonist (VKA) in patients with cancer among 8282 patients with acute venous thromboembolism (VTE) enrolled in the EINSTEIN programme. Rationale: Patients with cancer and VTE constitute a medical challenge for physicians because anticoagulant treatment is indicated to prevent recurrent VTE but is associated with a high risk of major bleeding. Methods: EINSTEIN DVT and EINSTEIN PE were randomized, event-driven, non-inferiority, open-label phase III studies. Patients were treated for 3, 6 or 12 months with rivaroxaban (15 mg twice daily for 21 days followed by 20 mg once daily) or enoxaparin/VKA (international normalized ratio 2.0–3.0) and followed for suspected recurrent VTE, bleeding and mortality. Cancer patients were classified as: active cancer at baseline (diagnosis or treatment within 6 months before enrolment or recurrent/metastatic cancer) or diagnosed during the study (n = 655); or a history of cancer (n = 469). Results: Recurrent VTE occurred with a similar incidence in the rivaroxaban and enoxaparin/VKA groups in patients with active cancer (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.35–1.30) and patients with a history of cancer (HR 0.98; 95% CI 0.28–3.43). In patients with active cancer, the risk of major bleeding was significantly reduced in the rivaroxaban group (HR 0.42; 95% CI 0.18–0.99), whereas it was similar between treatments in patients with a history of cancer (HR 0.23; 95% CI 0.03–2.06). Mortality occurred with a similar incidence between treatments in patients with active cancer (HR 0.93; 95% CI 0.64–1.35) and patients with a history of cancer (HR 1.12; 95% CI 0.30–4.22). Rivaroxaban Enoxaparin/VKA HR (95% CI) Recurrent VTE, n (%) Active cancer 16/354 (4.5) 20/301 (6.6) 0.67 (0.35–1.30) History of cancer 5/233 (2.1) 5/236 (2.1) 0.98 (0.28–3.43) Major bleeding, n (%) Active cancer 8/353 (2.3) 15/298 (5.0) 0.42 (0.18–0.99) History of cancer 1/231 (0.4) 4/236 (1.7) 0.23 (0.03–2.06) Mortality, n (%) Active cancer 58/354 (16.4) 53/301 (17.6) 0.93 (0.64–1.35) History of cancer 5/233 (2.1) 4/236 (1.7) 1.12 (0.30–4.22) Conclusions: Rivaroxaban had similar efficacy to enoxaparin/VKA in patients with VTE and active cancer or a history of cancer, but was associated with a significant reduction in major bleeding in patients with active cancer. Disclosure: M.H. Prins: is a consultant advisor for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Pfizer, Sanofi, Boehringer Ingelheim, GlaxoSmithKline (GSK), LEO, and ThromboGenics; T. Lensing, F. Misselwitz, A.F. Pap, M. Trajanovic and S.D. Berkowitz: is an employee of Bayer HealthCare Pharmaceuticals; P. Prandoni: has received consultant fees from Bayer Pharma, Daiichi Sankyo, Pfizer, Boehringer-Ingelheim and Sanofi-Aventis; A.T. Cohen: has received consultancy and clinical trial funding from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Daiichi, GSK, Johnson & Johnson, Mitsubishi Pharma, Pfizer, Portola, Sanofi-aventis, Schering-Plough & Takeda; B.L. Davidson: has received travel support from Bayer Healthcare, and is a steering committee member for Bayer HealthCare and Daiichi Sankyo;P. Wells: has received research support from Bristol-Myers Squibb, Pfizer; has participated on scientific advisory boards for Bayer Schering Pharma, Pfizer & Boehringer Ingelheim; and has received honoraria from Bayer Schering Pharma, Pfizer & Biomerieux.

Oral rivaroxaban for the treatment of symptomatic pulmonary embolism: are we ready?

Can an oral regimen of rivaroxaban be used for the treatment of symptomatic pulmonary embolism? Büller H, Prins M, Lensing A, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97. To determine the effectiveness and safety of oral rivaroxaban in the treatment of symptomatic pulmonary embolism when compared to current standard therapy.

Rivaroxaban versus enoxaparin/vitamin K antagonist therapy in patients with venous thromboembolism and renal impairment.

BackgroundPatients with renal impairment receiving classical anticoagulation for venous thromboembolism (VTE) are at increased risk of bleeding and possibly pulmonary embolism. We examined the efficacy and safety of oral rivaroxaban in patients with VTE with and without renal impairment.MethodsPrespecified subgroup analysis of the EINSTEIN DVT and EINSTEIN PE studies comparing fixed-dose rivaroxaban with enoxaparin/a vitamin K antagonist (VKA), performed in 8246 patients enrolled from 2007 to 2011 in 314 hospitals.ResultsOutcomes were recurrent VTE and major or clinically relevant nonmajor bleeding in patients with normal renal function (n = 5569; 67.3%) or mild (n = 2037; 24.6%), moderate (n = 636; 7.7%), or severe (n = 21; 0.3%) renal impairment. Rates of recurrent VTE were 1.8%, 2.8%, 3.3%, and 4.8% in patients with normal renal function and mild, moderate, and severe renal impairment, respectively (ptrend = 0.001). Hazard ratios for recurrent VTE were similar between treatment groups across renal function categories (pinteraction = 0.72). Major bleeding in rivaroxaban recipients occurred in 0.8%, 1.4%, 0.9%, and 0%, respectively (ptrend = 0.50). Respective rates in enoxaparin/VKA recipients were 1.0%, 3.0%, 3.9%, and 9.1% (ptrend < 0.001). Rivaroxaban–enoxaparin/VKA hazard ratios were 0.79 (95% confidence interval [CI] 0.46–1.36) for normal renal function, 0.44 (95% CI 0.24–0.84) for mild renal impairment, and 0.23 (95% CI 0.06–0.81) for moderate renal impairment (pinteraction = 0.034).ConclusionsPatients with symptomatic VTE and renal impairment are at increased risk of recurrent VTE. Renal impairment increased the risk of major bleeding in enoxaparin/VKA-treated patients but not in rivaroxaban-treated patients.Trial registrationNCT00440193 and NCT00439777.

Rivaroxaban

Rivaroxaban is an oral, direct Factor Xa inhibitor, which is at an advanced stage of clinical development for prevention and treatment of thromboembolic disorders. Two phase II studies, ODIXa-DVT and EINSTEIN DVT, assessed the efficacy and safety of oral rivaroxaban (once daily or twice daily) for treatment of acute deep-vein thrombosis (DVT). Population pharmacokinetic and pharmacodynamic analyses of rivaroxaban in patients in these two phase II studies were conducted to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban and the relationship between important patient covariates and model parameters. Exposure simulations in patients with atrial fibrillation (AF) were also performed in order to predict the exposure of rivaroxaban, using modified demographic data reflecting the characteristics of a typical AF population. A population pharmacokinetic model was developed using plasma samples from these patients. Various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with AF. Correlations between plasma rivaroxaban concentrations and the prothrombin time, Factor Xa activity, HepTest® and activated partial thromboplastin time were also described. The pharmacokinetics of rivaroxaban in patients with DVT were found to be consistent and predictable across all doses studied. The area under the plasma concentration-time curve (AUC) increased dose dependently. The same total daily doses given once daily achieved higher maximum plasma concentration (C(max)) values (∼20%) and lower trough (minimum) plasma concentration (C(trough)) values (∼60%) than when given twice daily; however, the 5th-95th percentile ranges for these parameters overlapped. Rivaroxaban clearance was moderately influenced by age and renal function, and the volume of distribution was influenced by age, body weight and sex; the effects were within the observed interindividual variability. Simulations in virtual patient populations with AF showed that a rivaroxaban dose of 15 mg once daily in patients with creatinine clearance of 30-49 mL/min would achieve AUC and C(max) values similar to those observed with 20 mg once daily in patients with normal renal function. The prothrombin time correlated almost linearly with plasma rivaroxaban concentrations (≤500 μg/L). Population analyses of phase II clinical data indicated that the pharmacokinetics and pharmacodynamics of all rivaroxaban doses were predictable and were affected by expected demographic factors in patients with acute DVT.

Rivaroxaban Compared with Enoxaparin for the Prevention of Venous Thromboembolism In Acutely Ill Medical Patients: MAGELLAN Study Methodology

AbstractAbstract 3331 Background:The results of clinical trials comparing low molecular weight heparins or a pentasaccharide with placebo controls have provided compelling evidence for the benefits of pharmacologic thromboprophylaxis for 10–14 days in acutely ill medical patients (Samama et al. N Engl J Med 1999;341:793–800; Leizorovicz et al. Circulation 2004;110:874–879; Cohen et al. BMJ 2006;332:325–329). Oral rivaroxaban 10 mg once daily (od) has been shown to be effective and well tolerated for the prevention of venous thromboembolism (VTE) for 31–39 days after elective hip replacement (Eriksson et al. N Engl J Med 2008;358:2765–2775; Kakkar et al. Lancet 2008;372:31–39) and for 10–14 days after knee replacement surgery in adult patients (Lassen et al. N Engl J Med 2008;358:2776–2786; Turpie et al. Lancet 2009;373:1673–1680). Aims:To compare the efficacy and safety of thromboprophylaxis with oral rivaroxaban 10 mg od for (1) up to 14 days and (2) up to 39 days with subcutaneous enoxaparin 40 mg od for up to 14 days in patients with acute medical illness requiring hospitalization. Methods:MAGELLAN (Multicenter, rAndomized, parallel Group Efficacy and safety study for the prevention of venous thromboembolism in hospitalized acutely iLL medical patients comparing rivaroxabAN with enoxaparin) was a multinational, multicenter, randomized, double-blind, double-dummy, active comparator controlled study in patients with current reduced mobility that was likely to persist. All enrolled patients received study medication on day 1 (defined as the day of randomization), underwent mandatory bilateral lower limb venous ultrasonography on day 10±4 and on day 35±4, and were followed until day 90±7. Suspected symptomatic VTE was investigated promptly using appropriate vascular and pulmonary imaging procedures. The inclusion criteria were: age ≥40 years; immobilization; heart failure, active cancer, acute ischemic stroke, acute infection, acute inflammatory or rheumatic disorders, or acute respiratory insufficiency. Patients with acute ischemic stroke without leg paresis or paralysis, acute infection, acute inflammatory or rheumatic disorders, or acute respiratory insufficiency required at least 1 additional risk factor for VTE, e.g. age ≥75 years, previous VTE, previous cancer or heart failure, severe venous disease, thrombophilia, recent major surgery or serious trauma, hormone replacement therapy or morbid obesity (body mass index ≥35 kg/m2). The exclusion criteria included an increased risk of bleeding; prohibited drugs or procedures, e.g. anticoagulant therapy; and concomitant conditions or diseases, e.g. allergies, severe renal or liver disease. The primary efficacy outcome was the composite of asymptomatic proximal deep vein thrombosis (DVT) detected by mandatory venous ultrasonography, symptomatic proximal and distal DVT, symptomatic pulmonary embolism, and fatal VTE reported during the treatment phase of the study. There were 2 efficacy analysis populations, pertaining to the 2 primary efficacy endpoints. The study was powered at the 90% level to show non-inferiority at day 10±4 and superiority at day 35±4. The primary safety outcome was the composite of major bleeding events and clinically relevant non-major bleeding events. Sparse pharmacokinetic/pharmacodynamic sampling was performed by measuring rivaroxaban levels at peak and trough time points in all patients. In selected centers, a full pharmacokinetic/pharmacodynamic profile was performed. Pharmacogenetic and health economic outcomes were also assessed. Results:The first patient was enrolled in December 2007. As of July 2010, 8,101 subjects have been enrolled in the study from 556 centers in 52 countries. The mean age of patients is approximately 69 years, and around 46% are female. Approximate distributions of the acute medical conditions are as follows: 34% have heart failure, 32% have acute infectious diseases, 24% have acute respiratory insufficiency, 17% have acute ischemic stroke, 8% have active cancer, and 5% have acute inflammatory and rheumatic diseases. Conclusions:MAGELLAN will determine the efficacy and safety of oral rivaroxaban (short- and extended-duration regimens) compared with the current standard of care in a diverse population of acutely ill medical patients with reduced mobility and other risk factors for venous thromboembolic disease. Disclosures:Cohen:Bayer Schering Pharma: Consultancy, Research Funding; Johnson and Johnson: Consultancy, Research Funding. Spiro:Bayer Healthcare Pharmaceuticals Inc.: Employment. Büller:Bayer Schering Pharma: Consultancy, Research Funding. Haskell:Johnson & Johnson Pharmaceutical Research & Development L.L.C.: Employment. Hu:Bayer Schering Pharma: Research Funding. Hull:Bayer Schering Pharma: Research Funding. Mebazaa:Bayer Schering Pharma: Research Funding. Merli:Bayer Schering Pharma: Research Funding. Schellong:Bayer Schering Pharma: Research Funding. Spyropoulos:Bayer Schering Pharma: Research Funding. Tapson:Bayer Schering Pharma: Research Funding.

Extended-Duration Thromboprophylaxis with Oral Rivaroxaban Versus Subcutaneous Enoxaparin After Total Hip Arthroplasty: RECORD1

Thromboprophylaxis is recommended for at least 10 days and up to 35 days following total hip arthroplasty (THA). Rivaroxaban is an oral, direct Factor Xa inhibitor that showed promise in early clinical trials. The purpose of this randomized, double-blind, double-dummy, phase III study was to compare the efficacy and safety of oral rivaroxaban with subcutaneous enoxaparin for 5 weeks, to prevent venous thromboembolism (VTE) in patients undergoing primary THA.

Oral Rivaroxaban Compared with Subcutaneous Enoxaparin for Extended Thromboprophylaxis after Total Hip Arthroplasty: The RECORD1 Trial.

Background Thromboprophylaxis for at least 10 days and for up to 4–5 weeks is recommended after total hip arthroplasty (THA). Rivaroxaban is an oral, direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. RECORD1 was a phase III, multinational, randomized, double-blind, double-dummy trial, conducted to determine the efficacy and safety of oral rivaroxaban, compared with subcutaneous enoxaparin, for 5 weeks of thromboprophylaxis in patients undergoing THA.Methods Patients received rivaroxaban 10 mg beginning 6–8 hours after surgery and once daily (od) thereafter, or enoxaparin 40 mg od, beginning the evening before surgery (restarting 6–8 hours after surgery). Therapy continued for 35±4 days and mandatory, bilateral venography was conducted the next day. The primary efficacy endpoint was the composite of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and all-cause mortality. The primary efficacy analysis was a test for non-inferiority in the per-protocol (PP) population, followed by a test for superiority in the modified intention-to-treat (mITT) population. The main secondary efficacy endpoint was major venous thromboembolism (VTE): the composite of proximal DVT, non-fatal PE and VTE-related death. Major and non-major bleeding during the active treatment period were the primary and secondary safety endpoints, respectively.Results A total of 4541 patients were randomized; 4433 were eligible for the safety population, 3153 for the mITT population, and 3029 for the PP population. The criteria for non-inferiority were met and testing for superiority was performed. Rivaroxaban significantly reduced the incidence of the primary efficacy endpoint (p<0.001) and major VTE (p<0.001), compared with enoxaparin, in the mITT population (Table). The incidence of major and non-major bleeding events was similar in both groups (Table). Conclusions Rivaroxaban was significantly more effective than enoxaparin for extended prophylaxis after THA, with a similar safety profile. This is the first pivotal trial to demonstrate the efficacy and safety of a fixed, unmonitored dose of an oral, direct Factor Xa inhibitor - rivaroxaban - for extended thromboprophylaxis after THA.Rivaroxaban 10mg od % (n/N)Enoxaparin 40 mg od % (n/N)Relative risk reduction % (95% CI)P-value for differenceDVT, non-fatal PE, and all-cause mortality1.1% (18/1595)3.7% (58/1558)70% (49–82%)P<0.001Major VTE0.2% (4/1686)2.0% (33/1678)88% (66–96%)P<0.001Major bleeding0.3% (6/2209)0.1% (2/2224)-P=0.178Non-major bleeding5.8% (128/2209)5.8% (129/2224)-P=1.000