rivaroxaban and Venous-Thromboembolism

Direct oral anticoagulants (DOACs) are widely used to treat venous thromboembolism (VTE) in adults. Little attention is given to pediatric VTE (PVTE). The objective of this study is to study the efficacy and safety of DOACs in published PVTE randomized control trials (RCTs). PubMed, Embase, China National Knowledge Infrastructure, the Cochrane Library, SinoMed, and ClinicalTrials.gov were searched until 2021, to identify RCTs that enrolled patients with VTE <18 years of age who received DOACs versus standard anticoagulation. Outcomes were evaluated using the Mantel-Haenszel method of random-effects model. Our study evaluated seven RCTs that included 1139 cases of PVTE, which had a low risk of publication and assessment bias. Compared with standard anticoagulation, patients receiving DOACs presented a lower rate of recurrent VTE (relative risk [RR], 0.42 [confidence interval {CI}, 0.20 to 0.89]), similar mortality rate (RR, 0.50 [CI, 0.07 to 3.57]), major bleeding (RR, 0.46 [CI, 0.14 to 1.57]), and higher clinically relevant nonmajor bleeding (RR, 2.71 [CI, 1.05 to 7.02]) with low heterogeneity. Limiting to subgroups, dabigatran and rivaroxaban yielded similar findings, except for a higher incidence of nonmajor bleeding during rivaroxaban use. DOACs could be an alternative to standard anticoagulation in PVTE. Dabigatran and rivaroxaban have similar effects. IMPACT: In venous thromboembolism (VTE), direct oral anticoagulants (DOACs) are widely used as a substitution for standard anticoagulation in most situations for adults; however, little attention is paid to the pediatric population. For pediatric VTE, previous meta-analyses have emphasized the epidemiology, risk factors, and the use of traditional anticoagulants, and seldom reported the use of novel oral anticoagulants. This is the first meta-analysis of randomized controlled trials that focuses on the efficacy outcomes and safety endpoints of DOACs compared with standard anticoagulation in pediatric VTE.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Child; Dabigatran; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Dabigatran; Gastrointestinal Hemorrhage; Humans; Rivaroxaban; Stroke; Venous Thromboembolism

Topics: Anticoagulants; Child; Humans; Nephrotic Syndrome; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

To systematically review the efficacy of 11 anticoagulants in the treatment of venous thromboembolism (VTE) after total hip or knee arthroplasty.. PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine databases were electronically searched for studies assessing the efficacy of different anticoagulants for the prevention of VTE after total hip or knee arthroplasty from January 1, 2010, to January 27, 2022. Two reviewers independently screened the literature, extracted data, and graded the evidence using Confidence in Network Meta-Analysis. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software.. A total of 61 articles were included. The results of network meta-analysis showed that apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban were the most effective anticoagulants for the prevention of deep vein thrombosis in patients undergoing total hip or knee arthroplasty (P < .05), while there was no difference in the efficacy among the anticoagulants for the prevention of pulmonary embolism (P > .05).. Apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban have the best efficacy for the prevention of VTE after total hip or knee arthroplasty.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Fondaparinux; Humans; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism

To summarize the incidence, risk factors, diagnosis methods, prophylaxis methods, and treatment of venous thromboembolism (VTE) following arthroscopic shoulder surgery.. Literature on VTE after arthroscopic shoulder surgeries was summarized, and all primary full-text articles reporting at least 1 case of deep vein thrombosis (DVT) or pulmonary embolism (PE) after arthroscopic shoulder surgeries were included. Articles were critically appraised and systematically analyzed to determine the incidence, risk factors, diagnosis, prophylaxis, and management of VTE following arthroscopic shoulder surgeries.. Based on the included studies, the incidence rate of VTE after arthroscopic shoulder surgeries is relatively low. The risk factors for VTE are still unclear. CT/CTA and ultrasound were the mainstream diagnosis methods for PE and DVT, respectively. Current evidence shows that chemical prophylaxis did not deliver significant benefits, since none of the existing studies reported statistically different results. High-quality studies focusing on the prophylaxis and management of VTE population undergoing arthroscopic shoulder surgeries should be done in the future.

Topics: Aged; Anticoagulants; Humans; Incidence; Pulmonary Embolism; Risk Factors; Rivaroxaban; Shoulder; Venous Thromboembolism; Warfarin

Direct oral anticoagulants (DOACs) have been used for venous thromboembolism (VTE) in Thailand. However, they have not been listed in the National List of Essential Medicines (NLEM). A cost-effectiveness analysis is needed to aid policymakers in deciding whether DOACs should be listed in the NLEM. This study aimed to assess the cost-effectiveness of DOACs for patients with VTE in Thailand.. A cohort-based state transition model was constructed from a societal perspective with a lifetime horizon. All available DOACs, including apixaban, rivaroxaban, edoxaban, and dabigatran, were compared with warfarin. A 6-month cycle length was used to capture all costs and health outcomes. The model consisted of nine health states, including VTE on treatment, VTE off treatment, recurrent VTE, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial bleeding, post-intracranial bleeding, chronic thromboembolic pulmonary hypertension, and death. All inputs were based on a comprehensive literature review. The model outcomes included total cost and quality-adjusted life-years (QALYs) with a 3% annual discount rate. A fully incremental cost-effectiveness analysis and the incremental cost-effectiveness ratio (ICER) per QALY gained were calculated at a willingness-to-pay (WTP) of THB 160,000/QALY ($5003). The robustness of the findings was assessed using deterministic and probabilistic sensitivity analyses.. All DOACs were associated with a decreased risk of VTE recurrence and intracranial hemorrhage. In the base-case analysis, apixaban could increase 0.16 QALYs compared with warfarin. An ICER for apixaban was 269,809 Thai baht (THB)/QALY ($8437/QALY). Rivaroxaban had a better QALY than warfarin at 0.09 QALYs with an ICER of 757,363 THB/QALY ($23,682/QALY). Edoxaban and dabigatran could also increase by 0.10 QALYs with an ICER of 709,945 THB ($22,200) and 707,145 THB ($22,122)/QALY, respectively. Our probabilistic sensitivity analyses indicated that warfarin had a 99.8% possibility of being cost-effective, while apixaban had a 0.2% possibility of being cost-effective at the current WTP. Other DOACs had no possibility of being cost-effective.. All DOACs were not cost-effective for VTE treatment at the current WTP in Thailand. Apixaban is likely to be the best option among DOACs.

Topics: Anticoagulants; Cost-Benefit Analysis; Dabigatran; Humans; Pyridones; Quality-Adjusted Life Years; Rivaroxaban; Thailand; Venous Thromboembolism; Warfarin

This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion.. Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

Direct oral anticoagulants (DOACs) have become the cornerstone for prevention of thromboembolic events in patients with atrial fibrillation and patients with a history of venous thromboembolism. However, studies show that DOAC prescriptions are commonly inconsistent with guideline recommendations. DOAC dosing in the acutely ill patient could impose an even greater challenge. In this review, we describe the prevalence of inappropriate inpatient prescribing of DOACs and the associated rationales, predictors and clinical consequences. With the aim of promoting appropriate prescriptions of DOACs to hospitalized patients, we further outline DOAC dose reduction criteria justified by various guidelines, illustrating the complexities of appropriate dosing, especially in acutely ill patients. Moreover, we will discuss the impact of anticoagulant stewardship programs and the vital role that pharmacists may play in optimizing inpatient DOAC treatment.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Inappropriate Prescribing; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism

Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT.. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022.. We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome.. We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortal

Topics: Anticoagulants; Antithrombins; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasm Recurrence, Local; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

To conduct an update of the ASCO venous thromboembolism (VTE) guideline.. After publication of potentially practice-changing clinical trials, identified through ASCO's signals approach to updating, an updated systematic review was performed for two guideline questions: perioperative thromboprophylaxis and treatment of VTE. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) published between November 1, 2018, and June 6, 2022.. Five RCTs provided information that contributed to changes to the 2019 recommendations. Two RCTs addressed direct factor Xa inhibitors (either rivaroxaban or apixaban) for extended thromboprophylaxis after surgery. Each of these postoperative trials had important limitations but suggested that these two oral anticoagulants are safe and effective in the settings studied. An additional three RCTs addressed apixaban in the setting of VTE treatment. Apixaban was effective in reducing the risk of recurrent VTE, with a low risk of major bleeding.. Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation. Apixaban was also added as an option for the treatment of VTE, with high quality of evidence and a strong recommendation.Additional information is available at www.asco.org/supportive-care-guidelines.

Topics: Anticoagulants; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

Patients with chronic kidney disease are at an increased risk of venous thromboembolism (VTE). The factor Xa inhibitor rivaroxaban has been shown to provide similar efficacy and a lower risk of bleeding compared with vitamin K antagonists for the treatment and prevention of VTE. Rivaroxaban has been studied in patients with varying degrees of renal impairment, and this review summarizes current knowledge supporting its use in patients with severe renal impairment (creatinine clearance [CrCl] of 15 to < 30 mL/min) for the prevention, treatment, or prophylaxis of VTE. Clinical pharmacology studies have demonstrated an increase in rivaroxaban systemic exposure, factor Xa inhibition, and prothrombin time with decreasing renal function. These changes reach a plateau with comparable increases in exposure among individuals with moderate or severe renal impairment and end-stage renal disease. The clinical development program for the treatment and prevention of VTE as well as prophylaxis of deep vein thrombosis (DVT) following orthopedic surgery excluded patients with CrCl < 30 mL/min; however, a limited number of patients with severe renal impairment were enrolled. Efficacy outcomes in these patients with severe renal impairment were not meaningfully different from those of patients with higher levels of renal function. There was also no increase in the incidence of major bleeding with rivaroxaban in patients with CrCl < 30 mL/min. Taken together, these pharmacological and clinical data suggest that in patients with severe renal impairment, the approved dosages of rivaroxaban can be used in the treatment and prevention of VTE and for prophylaxis of DVT after hip or knee replacement surgery.

Topics: Anticoagulants; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Kidney; Renal Insufficiency; Rivaroxaban; Venous Thromboembolism

Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased risk of thrombotic events. Also, more bleeding events are observed in those who receive anticoagulation compared to those without cancer. In the treatment of cancer-associated thrombosis, direct oral anticoagulants (DOACs) have been found to be at least as effective as low-molecular weight heparins, which became the standard of care after several trials demonstrated superiority over vitamin K antagonists. Non-inferiority compared to low-molecular weight heparins has been shown for rivaroxaban, edoxaban and apixaban with a signal of fewer recurrent thrombotic events, albeit with an increase in bleeding events. Yet, potentially major pharmacokinetic drug-drug interactions have been identified as a reason to withhold DOACs and to rather choose an alternative. Practical guidance on what constitutes a major pharmacokinetic interaction and/or how to deal with these interactions in clinical practice is limited. Hence, here we have provided a framework to allow clinicians to better deal with pharmacokinetic drug-drug interactions between DOACs and cancer therapies in the management of cancer-associated thrombosis. In this review we have discussed the current literature, how the pharmacokinetic profile links to the label information on DDI, and have provided a practical proposal, applied to a clinical case.

Topics: Administration, Oral; Anticoagulants; Drug Interactions; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).. In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.

Topics: Anticoagulants; Brain Neoplasms; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

Isolated distal deep vein thrombosis (IDDVT) is a frequent manifestation of venous thromboembolism (VTE), accounting for up to 50% cases of lower‑extremity deep vein thrombosis (DVT). As compared with proximal DVT, IDDVT is more frequently associated with transient risk factors and less often occurs unprovoked or in the presence of permanent risk factors. IDDVT generally carries a significantly lower risk of proximal extension, post‑thrombotic syndrome, and recurrence than proximal DVT. Nevertheless, some patient subgroups, such as those with active cancer, other predisposing permanent risk factors, prior VTE, unprovoked IDDVT, persistently restricted mobility, and trifurcation or bilateral involvement, exhibit a non‑negligible recurrence risk. Unlike in proximal DVT, the optimal therapeutic management of IDDVT remains uncertain. In clinical practice, the vast majority of IDDVT patients are managed with anticoagulation rather than with surveillance serial compression ultrasonography, which tends to be reserved to individuals at a high bleeding risk. Available data seem to favor anticoagulant therapy over no anticoagulation, thanks to a significant reduction in the risk for proximal extension and recurrence, without increased bleeding risk. Recent results of the RIDTS (Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis) randomized clinical trial with rivaroxaban further support the use of anticoagulant therapy for 3 months over shorter durations (eg, ≤6 weeks). In this review, we offer an updated overview of the epidemiology, risk factors, and clinical course of IDDVT, with a focus on the therapeutic management in light of current guideline recommendations and most recent evidence. We also present real‑life clinical cases of IDDVT with proposed therapeutic approaches, and highlight major challenges and gaps in this field.

Topics: Anticoagulants; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US).. We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin.. Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs.. This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Retrospective Studies; Rivaroxaban; Stroke; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

The conjunction of atrial fibrillation (AF) and venous thromboembolism (VTE) is common in clinical practice. Over the last 2 decades, a significant number of articles (2500) have been published about AF and VTE. To effectively analyze and present these vast amounts of information, this study uses bibliometric research methods to categorize and consolidate these publications. The number of publications has increased yearly, especially since 2012. The United States was the most prolific country, with 1054 studies published. The most productive institution was McMaster University. Gregory Y.H. Lip was the most prolific author. The keyword analysis identified that the research focuses from 2003 to 2014 were factor Xa inhibitor, dabigatran etexilate, direct thrombin inhibitor, double-blind, deep vein thrombosis, molecular weight heparin, stroke prevention, etc. From 2015 to 2016, research mainly focused on venous thromboembolism, antithrombotic therapy, anticoagulant, warfarin, atrial fibrillation, stroke, and pulmonary embolism. Studies during 2017 to 2022 focused on apixaban, direct oral anticoagulant, rivaroxaban, dabigatran, hemorrhage, edoxaban, medicine efficacy and safety, risk factors, clinical management, and vitamin K antagonists. Since 2018, novel oral anticoagulants have been the most commonly used keywords. On the whole, most studies of AF and VTE focus on pathogenesis and therapeutic drugs. The causal relationship between AF and VTE, the effectiveness and safety of novel oral anticoagulants in the treatments, the anticoagulant regimen of AF and VTE co-disease, and the treatment regimen for vulnerable populations such as the elderly or obese people were the focus of current research and will continue to be the central point of future research.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Venous Thromboembolism; Warfarin

Current evidence-based clinical practice guidelines recommend the use of both low-molecular-weight heparin (LMWH) and direct factor Xa inhibitors (apixapan, edoxaban and rivaroxaban) as first-line options for the treatment of venous thromboembolism (VTE) in patients with cancer. However, most of these guidelines refer to the general cancer patient population and provide limited guidance for specific subgroups of patients at particularly high risk of bleeding, such as those with gastrointestinal cancers, primary or metastatic brain tumors, thrombocytopenia, or renal impairment. In these complex populations, the management of cancer-associated thrombosis (CAT) poses unique challenges and requires a nuanced approach based on the primum non nocere principle. This comprehensive review critically examines the relevant literature and discusses the therapeutic options currently available for the management of CAT in these special situations.

Topics: Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE).. PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.. Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 - 4.12) and edoxaban (OR 2.64, 95% CI 1.36 - 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 - 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6).. For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Network Meta-Analysis; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

The real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have reported conflicting findings. Our study aimed to provide the direct comparison evidence of different NOACs for VTE patients in clinical practice settings.. Search of the medical literature was conducted using PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library from inception to March 22, 2021. Among the 19,996 citations retrieved, a total of 63,144 patients from 6 studies were analyzed. Clinical outcomes included recurrent VTE, death, and different bleeding events.. Adjusted hazard ratio (HR) analysis suggested that apixaban had significant lower bleeding riskthan rivaroxaban (major, minor and any bleeding: HR = 0.61, 0.56, 0.70; p = 0.008, < 0.0001, 0.006, respectively), but no statistics difference found in recurrent VTE events (HR = 1.02, 95% confidence interval (CI) 0.71-1.47, p = 0.93). There was no significant difference of major bleeding between dabigatran and rivaroxaban (odds ratios (OR) = 0.41, 95% CI 0.09-1.90, p = 0.25), apixaban and dabigatran (OR 0.64, 95% CI 0.15-2.72, p = 0.83). No significant difference was found in the comparison of edoxaban and other NOACs in VTE recurrence, major bleeding and composite outcome.. In the prevention of bleeding events, apixaban was associated with a lower risk than rivaroxaban, but equivalent efficacy for different NOACs in prevention of recurrent VTE. Evidence generated from the meta-analysis based on real-world data can help to guide selection between apixaban and rivaroxaban in routine clinical practice.. This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology statements and was registered with PROSPERO (CRD42019140553).

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism

This review summarizes current evidence and guideline recommendations concerning diagnosis and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). For the diagnostic pathway, evidence-based algorithms should be employed, based on the assessment of pretest clinical probability. D‑dimer tests may reduce the need for subsequent diagnostic procedures. Clinical management of PE is guided by risk stratification according to early mortality. Lactate levels may be helpful for further risk stratification. The acute treatment of venous thromboembolism (VTE) is commenced with intensified anticoagulation (AC), either with parenteral AC or higher initial doses of apixaban or rivaroxaban. All patients with VTE should receive the anticoagulation maintenance therapy for 3-6 months, while the duration of the subsequent secondary prophylaxis depends on the presumed risk of VTE recurrence and bleeding. Compression therapy is used to prevent postthrombotic syndrome. Acute revascularization procedures are limited to rare special cases. In obese patients up to 150 kg, standard doses of rivaroxaban and apixaban are appropriate. In cancer-associated thromboembolism (CAT), the previous guideline recommendation to use low molecular weight heparin (LMWH) for 3-6 months is now broadened with the recommendation for factor Xa inhibitors, with the caveat for gastrointestinal and urothelial cancer or expected drug-drug interactions with the anticancer treatment. Here, and in unstable clinical situations, LMWH is preferred.. In dieser Übersichtsarbeit werden die aktuelle Evidenz und Empfehlungen aus aktuellen Leitlinien zur Diagnostik und Therapie von tiefer Venenthrombose (TVT) und Lungenembolie (LE) zusammengefasst. Für den Diagnoseprozess soll ein evidenzbasierter Algorithmus verwendet werden, der mit der Abschätzung der klinischen Wahrscheinlichkeit beginnt. Unter Berücksichtigung des D‑Dimer-Tests kann die Notwendigkeit für die nachfolgende bildgebende Diagnostik reduziert werden. Bei der LE leitet die Stratifizierung entsprechend der Frühmortalität das weitere klinische Management. Die Messung von Laktat kann für diese Risikoeinschätzung hilfreich sein. Die Akuttherapie der venösen Thromboembolie (VTE) erfolgt intensiviert entweder mit parenteralen Antikoagulanzien oder erhöhten Dosierungen von Apixaban oder Rivaroxaban. Alle Patienten mit VTE sollten eine Erhaltungstherapie über 3–6 Monate erhalten, da bei einer Antikoagulation (AK) < 3 Monaten ein hohes Rezidivrisiko besteht. Die Dauer der anschließenden Sekundärprophylaxe richtet sich nach dem mutmaßlichen VTE-Rezidivrisiko einerseits und dem Blutungsrisiko andererseits. Weiterhin wird eine Kompressionstherapie zur Verhinderung des postthrombotischen Syndroms empfohlen, akut revaskularisierende Eingriffe sind Sonderfällen vorbehalten. Bei Adipositas bis 150 kg werden Standarddosen von Rivaroxaban und Apixaban als geeignet vorgeschlagen. Bei der krebsassoziierten Thromboembolie wird die bisherige Leitlinienempfehlung für niedermolekulare Heparine (NMH) über 3–6 Monate ergänzt durch die Empfehlung für Faktor-Xa-Inhibitoren, allerdings mit Vorsicht bei gastrointestinalen und urothelialen Tumoren oder erwarteten Wechselwirkungen mit der Antikrebstherapie. Hier und in instabilen Phasen werden NMH bevorzugt.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

A systematic review and meta-analysis was performed to determine the role of thromboprophylaxis in the prevention of venous thromboembolism in patients undergoing varicose vein interventions.. PUBMED, EMBASE and Web of Science were searched for comparative studies of patients undergoing varicose vein interventions and received either thromboprophylaxis or no thromboprophylaxis. Data were collected on the number of thrombotic events including deep vein thrombosis (DVT), pulmonary embolism (PE) and endothermal heat-induced thrombosis (EHIT) as well as bleeding events. The primary outcomes for the meta-analysis were the risk of all thrombotic events, risk of DVT and risk of bleeding. Pooled risk ratios were calculated using random effects modelling.. Eight studies (6479 participants) were included. The use of thromboprophylaxis reduces the risk of all thrombotic events (Pooled risk ratio = 0.63, 95% Confidence interval [CI], 0.04-10.43) and the risk of DVT (Pooled risk ratio = 0.59, 95% CI, 0.08-4.60) with no increased risk of bleeding (Pooled risk ratio = 0.66, 95% CI, 0.06-7.21]. Rivaroxaban has similar efficacy in the prevention of DVT compared to Fondaparinux in patients undergoing endovenous ablation of varicose veins (Pooled risk ratio = 0.68, 95% CI, 0.06-7.41). An extended course of thromboprophylaxis reduces the risk of developing DVT compared to a short course (Pooled risk ratio = 1.40, 95% CI, 0.44-4.46). However, the two studies reporting on the duration of thromboprophylaxis did not stratify patients according to their risk of developing venous thromboembolism.. The use of thromboprophylaxis in patients undergoing varicose vein interventions reduces the risk of venous thromboembolism with no significant increase in the risk of bleeding. However, the included studies were underpowered with high to moderate risk of bias. Therefore, more randomised controlled trials with a large sample size are needed in order to provide high quality evidence for clinical practice.

Topics: Humans; Pulmonary Embolism; Rivaroxaban; Varicose Veins; Venous Thromboembolism

Venous thromboembolism (VTE) is a serious national and international public health issue. Major orthopedic surgeries, such as a total hip (THA) and knee (TKA) arthroplasties, are associated with an increased risk of VTE, long-term complications, functional disability, and death resulting from hypercoagulability by surgical trauma. This pharmacoeconomic analysis aimed to identify the most cost-effective anticoagulant alternative in preventing VTE in patients undergoing THA and TKA.. A decision tree model was developed, comparing direct oral anticoagulants (rivaroxaban, apixaban, and dabigatran) with enoxaparin, with separate THA and TKA models a 3-month time horizon from the perspective of the Brazilian National Health System. The results were presented as incremental cost-effectiveness ratio (ICER), and the outcomes analyzed were avoided complications (ACs) after thromboprophylaxis. Comparative effectiveness was obtained from a published meta-analysis. A willingness to pay value of approximately R$ 15 000.00 was used per AC, and a probabilistic sensitivity analysis with the Monte Carlo simulation was conducted.. Apixaban was the anticoagulant that presented the best ICER for patients undergoing THA (R$ 207.52/AC) and TKA (R$ 133.59/AC), followed by rivaroxaban (R$ 347.21/AC), dabigatran (R$ 372.56/AC), and enoxaparin (R$ 711.44/AC) for THA and by dabigatran (R$ 194.07/AC), rivaroxaban (R$ 221.12/AC), and enoxaparin (R$ 747.25/AC) for TKA. After ICER analysis, apixaban prevails over the other technologies analyzed for both surgical procedures, confirmed after sensitivity analysis.. Our model suggests that, in the Brazilian National Health System, apixaban is the most cost-effective alternative in preventing VTE after THA and TKA.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Brazil; Cost-Benefit Analysis; Dabigatran; Enoxaparin; Humans; Rivaroxaban; Venous Thromboembolism

Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs.. Among 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities.. Dose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Rivaroxaban; Stroke; Venous Thromboembolism

Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice.. Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals.. A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]).. This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Lower limb trauma requiring immobilization is a significant contributor to overall venous thromboembolism (VTE) burden. The clinical effectiveness of thromboprophylaxis for this indication and the optimal agent strategy are still a matter of debate. Our main objective was to assess the efficacy of pharmacological thromboprophylaxis to prevent VTE in patients with isolated temporary lower limb immobilization after trauma. We aimed to estimate and compare the clinical efficacy and the safety of the different thromboprophylactic treatments to determine the best strategy.. We conducted a systematic review and a Bayesian network meta-analysis (NMA) including all available randomized trials comparing a pharmacological thromboprophylactic treatment to placebo or to no treatment in patients with leg immobilization after trauma. We searched Medline, Embase, and Web of Science until July 2021. Only RCT or observational studies with analysis of confounding factors including adult patients requiring temporary immobilization for an isolated lower limb injury treated conservatively or surgically and assessing pharmacological thromboprophylactic agents or placebo or no treatment were eligible for inclusion. The primary endpoint was the incidence of major VTE (proximal deep vein thrombosis, symptomatic VTE, and pulmonary embolism-related death). We extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses for NMA and appraised selected trials with the Cochrane review handbook. Fourteen studies were included (8,198 patients). Compared to the control group, rivaroxaban, fondaparinux, and low molecular weight heparins were associated with a significant risk reduction of major VTE with an odds ratio of 0.02 (95% credible interval (CrI) 0.00 to 0.19), 0.22 (95% CrI 0.06 to 0.65), and 0.32 (95% CrI 0.15 to 0.56), respectively. No increase of the major bleeding risk was observed with either treatment. Rivaroxaban has the highest likelihood of being ranked top in terms of efficacy and net clinical benefit. The main limitation is that the network had as many indirect comparisons as direct comparisons.. This NMA confirms the favorable benefit/risk ratio of thromboprophylaxis for patients with leg immobilization after trauma with the highest level of evidence for rivaroxaban.. PROSPERO CRD42021257669.

Topics: Adult; Anticoagulants; Bayes Theorem; Humans; Leg; Lower Extremity; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Thromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious. We aim to review and analyse literature on the efficacy and safety of DOACs compared with VKAs in treating patients with APS. A literature search was performed from inception to 31 December 2021. Subgroups were analysed based on the risk stratification of APS profiles and different DOAC types. A total of nine studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis [risk ratio = 3.65, 95% confidence interval (95% CI): 1.49-8.93; I2  = 29%, P  = 0.005] compared with those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR = 2.63; 95% CI: 1.56-4.42; I2  = 0, P  = 0.0003), particularly recurrent arterial thromboses (RR = 4.52; 95% CI: 1.99-10.29; I2  = 0, P  = 0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences. In the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Dabigatran; Fibrinolytic Agents; Hemorrhage; Humans; Rivaroxaban; Thrombosis; Venous Thromboembolism; Vitamin K

Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and, in suitable cases, to assist the diagnosis of persistent knee pain. There is a small risk of thromboembolic events associated with KA. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This is an update of an earlier Cochrane Review.. To evaluate the efficacy and safety of interventions - whether mechanical, pharmacological, or a combination of both - for thromboprophylaxis in adults undergoing KA.. We used standard, extensive Cochrane search methods. The latest search date was 1 June 2021.. We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), blinded or unblinded, of all types of interventions used to prevent deep vein thrombosis (DVT) in men and women aged 18 years and older undergoing KA.. We used standard Cochrane methods. Our primary outcomes were pulmonary embolism (PE), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Our secondary outcomes were adverse effects, major bleeding, and minor bleeding. We used GRADE criteria to assess the certainty of the evidence.. We did not identify any new studies for this update. This review includes eight studies involving 3818 adults with no history of thromboembolic disease. Five studies compared daily subcutaneous low-molecular-weight heparin (LMWH) versus no prophylaxis; one study compared oral rivaroxaban 10 mg versus placebo; one study compared daily subcutaneous LMWH versus graduated compression stockings; and one study compared aspirin versus no prophylaxis. The incidence of PE in all studies combined was low, with seven cases in 3818 participants. There were no deaths in any of the intervention or control groups. Low-molecular-weight heparin versus no prophylaxis When compared with no prophylaxis, LMWH probably results in little to no difference in the incidence of PE in people undergoing KA (risk ratio [RR] 1.81, 95% confidence interval [CI] 0.49 to 6.65; 3 studies, 1820 participants; moderate-certainty evidence). LMWH may make little or no difference to the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 4 studies, 1848 participants; low-certainty evidence). It is uncertain whether LMWH reduces the risk of asymptomatic DVT (RR 0.14, 95% CI 0.03 to 0.61; 2 studies, 369 participants; very low-certainty evidence). LMWH probably makes little or no difference to the risk of all adverse effects combined (RR 1.85, 95% CI 0.95 to 3.59; 5 studies, 1978 participants; moderate-certainty evidence), major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; moderate-certainty evidence), or minor bleeding (RR 1.79, 95% CI 0.84 to 3.84; 5 studies, 1978 participants; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. There were no cases of PE reported. Rivaroxaban probably led to little or no difference in symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence). It is uncertain whether rivaroxaban reduces the risk of asymptomatic DVT because the certainty of the evidence is very low (RR 0.95, 95% CI 0.06 to 15.01). The study only reported bleeding adverse effects. No major bleeds occurred in either group, and rivaroxaban probably made little or no difference to minor bleeding (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus no prophylaxis One study compared aspirin with no prophylaxis. There were no PE, DVT or asymptomatic events detected in either group. The study authors reported adverse effects including pain and swelling, but wit. There is a small risk that healthy adults undergoing KA will develop venous thromboembolism (PE or DVT). We found moderate- to low-certainty evidence of little or no benefit from LMWH, or rivaroxaban in reducing this small risk of PE or symptomatic DVT. The studies provided very low-certainty evidence that LMWH may reduce the risk of asymptomatic DVT compared to no prophylaxis, but it is uncertain how this directly relates to incidence of DVT or PE in healthy people undergoing KA. There is probably little or no difference in adverse effects (including major and minor bleeding), but data relating to these outcomes were limited by low numbers of events in the studies reporting these outcomes.

Topics: Adult; Anticoagulants; Arthroscopy; Aspirin; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Pain; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15-25% of all VTE cases. For decades, the standard treatment for CAT used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score ≥2 prior to starting new chemotherapy, low bleeding risk, no interfering medications).

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism

The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear.. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA).. We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8).. For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism; Warfarin

This review article describes insights into the prevention and treatment of cancer-associated venous thromboembolism (VTE) with direct factor Xa inhibitors (FXaI) and refers in particular to the CALLISTO study program with rivaroxaban. CALLISTO includes randomized clinical trials on different topics as well as real-world evidence.Prevention and treatment of cancer-associated VTE have so far relied on low molecular weight heparins (LMWH). Meanwhile, randomized controlled trials have found comparable to superior efficacy of FXaI vs. LMWH, and the findings are now being incorporated into recommendations and guidelines. A possibly increased risk of bleeding, especially in patients with unresected gastrointestinal or urogenital tumors, should be considered. This was first observed during therapy with FXaI but can also affect LMWH. The selection of suitable patients and the optimization of treatment pathways are therefore of great importance.. Diese Übersichtsarbeit beschreibt Erkenntnisse zur Prävention und Therapie der tumorassoziierten venösen Thromboembolie (VTE) mit direkten Faktor-Xa-Inhibitoren (FXaI) und bezieht sich insbesondere auf das Studienprogramm CALLISTO mit Rivaroxaban. CALLISTO umfasst randomisierte klinische Prüfungen unterschiedlicher Fragestellungen sowie Real-World-Evidenz.Prävention und Therapie der tumorassoziierten VTE beruhten bisher auf niedermolekul1933aren Heparinen (NMH). Randomisierte kontrollierte Studien zeigten nun eine vergleichbare bis überlegene Wirksamkeit von FXaI vs. NMH. Die Erkenntnisse finden mittlerweile Eingang in Empfehlungen und Leitlinien. Zu beachten ist ein ggf. erhöhtes Blutungsrisiko, vor allem bei Patienten mit nicht resezierten gastrointestinalen oder urogenitalen Tumoren. Dieses wurde bei der Therapie mit FXaI zuerst beobachtet, kann jedoch auch NMH betreffen. Der Selektion geeigneter Patienten und der Optimierung von Behandlungspfaden kommt daher eine hohe Bedeutung zu.

Topics: Anticoagulants; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

The results of associations between new oral anticoagulants (NOACs) and wound complications after total joint arthroplasty remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials to make comparisons with low molecular weight heparins (LMWH) on the clinical outcomes of total wound complications, together with other efficacy and safety endpoints to further evaluate the safety and efficacy of NOACs.. This meta-analysis was conducted based on a published protocol (PROSPERO: CRD42019140841). We searched for available articles in PubMed, Embase and Cochrane Library through Jun 62 021. Random-effects meta-analyses, including subgroup analyses, were conducted to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for specific doses of NOACs.. We retrieved 1683 studies, of which 20 were eligible for inclusion. We found that apixaban was associated with a lower incidence of total wound complications compared with LMWH (RR = 0.81; 95% CI: 0.65-1.00), while dabigatran and rivaroxaban did not increase the risk of total wound complications. In addition, apixaban was associated with a reduction in the risk of major/clinically relevant nonmajor bleeding events compared to LMWH (RR = 0.80, 95% CI: 0.65-0.99), while rivaroxaban increased the risk for major/clinically relevant nonmajor bleeding events (RR = 1.23, 95% CI: 1.02-1.50). Moreover, all 4 NOACs were associated with lower incidences of major venous thromboembolism compared with LMWH.. A lower risk of wound complications was detected for apixaban, while dabigatran and rivaroxaban did not increase the risk when compared with LMWH. The efficacy of 4 NOACs was broadly similar.

Topics: Administration, Oral; Anticoagulants; Arthroplasty; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer. Moreover, management of VTE is frequently connected with complications, namely risk of recurrent VTE and bleeding. Low molecular weight heparins (LMWH) therapy administrated for 3-6 months is currently considered a standard for the treatment of cancer-associated VTE (CA-VTE). Direct oral factor Xa inhibitors (FXaI) apixaban, edoxaban and rivaroxaban have emerged as a new possibility for long-term antithrombotic therapy for VTE. These agents expose several advantages in individuals with cancer, and might overcome several disadvantages connected with LMWH therapy.. First clinical studies with oral FXaI for the treatment of CA-VTE with very promising results were recently published. The article summarizes current data regarding the use of oral FXaI in the treatment of CA-VTE.

Topics: Administration, Oral; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Venous Thromboembolism

Betrixaban and rivaroxaban are the direct anticoagulants approved in the United States for extended venous thromboembolism (VTE) prophylaxis among acutely ill medical patients. The efficacy and safety in specific subgroups remain unclear.. A meta-analysis of 3 randomized trials involving extended thromboprophylaxis with betrixaban or rivaroxaban versus enoxaparin for medically ill patients was performed to compare VTE (composite of asymptomatic proximal and symptomatic deep vein thrombosis, pulmonary embolism, or VTE-related death) and major bleeding in subgroups by baseline D-dimer, age, sex, and major medical illness on hospitalization. Risk difference (RD) was computed with the Mantel-Haenszel method by fitting a fixed-effect model. Heterogeneity of treatment effect across subgroups was examined using the nominal thresholds of P < 0.05 and I2 > 75%.. Compared with enoxaparin, extended betrixaban or rivaroxaban reduced VTE (RD = -1.51% [95% CI, -2.32% to -0.69%]; P = 0.0003) without excess major bleeding (RD = 0.12% [-0.05% to 0.29%]; P = 0.16). A significant effect modification was observed in the subgroups by D-dimer (P = 0.004) and age (P = 0.04). Patients with D-dimer >2× upper limit of normal (ULN) experienced a greater VTE reduction (RD = -2.39% [-3.57% to -1.21%]; P < 0.0001) than those with ≤2×ULN (RD = -0.26% [-1.08% to 0.56%]; P = 0.53). Similarly, patients aged ≥75 years had a greater VTE reduction (RD = -2.29% [-3.49% to -1.09%]; P = 0.0002) than those aged <75 years (RD = -0.63% [-1.70% to 0.44%]; P = 0.25). Treatment effect was consistent across the remaining subgroups.. A more favorable efficacy and comparable safety outcome associated with extended betrixaban or rivaroxaban were observed among medical inpatients with D-dimer >2×ULN or aged ≥75 years. D-dimer and advanced age may assist in decision-making on pharmacological thromboprophylaxis for hospitalized medical patients.

Topics: Anticoagulants; Benzamides; Humans; Pyridines; Risk Factors; Rivaroxaban; Venous Thromboembolism

To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients.. A literature search was conducted for studies evaluating VTE and bleeding outcomes with DOAC use in CKD and dialysis patients. Searches conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from inception to September 22, 2020.. Randomized controlled trials, cohort studies, and case series with ≥10 patients included.. From 7286 studies, nine studies met inclusion criteria. There was no significant difference between DOACs (dabigatran, rivaroxaban, apixaban) and warfarin for reducing recurrent VTE and bleeding events in moderate CKD patients. The risk of overall major bleeding increased when the degree of kidney impairment increased. There was no significant difference between apixaban and warfarin for VTE outcomes in dialysis patients.. There continues to be a controversial debate whether it may be more beneficial to use DOACs versus warfarin in CKD/dialysis patients with venous thromboembolism (VTE). The risk vs benefit of using DOACs in the CKD/ESKD population should continue to be evaluated for each individual patient.. Apixaban may be used cautiously as an alternative in acute VTE treatment in severe CKD patients. Insufficient evidence is available to suggest the use of dabigatran and rivaroxaban in this patient population. The benefit of using DOACs in this population for VTE treatment should be weighed against the potential bleeding risk in patients with CKD.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Renal Dialysis; Renal Insufficiency, Chronic; Rivaroxaban; Thrombosis; Venous Thromboembolism

To summarize the literature assessing the safety and efficacy of direct oral anticoagulants (DOACs) for the acute treatment and secondary prevention of venous thromboembolism (VTE) in select patients with hypercoagulable disorders.. An electronic PubMed literature search was conducted from January 2010 to July 2020 using the following keywords:. Articles were included if they reported clinical outcomes associated with cancer-associated VTE, antiphospholipid syndrome (APS), and other hereditary thrombophilias.. The safety and efficacy of using a DOAC is highly dependent on the type of hypercoagulable disease state. Current trials support the use of edoxaban, rivaroxaban, and apixaban for the treatment of cancer-associated thrombosis (CAT), with apixaban being preferred because of lower bleeding rates compared with standard of care. The use of DOACs, especially rivaroxaban, have been associated with worse outcomes in patients with APS, whereas data on DOAC use in hereditary thrombophilia remains scarce and limited to low-risk patients.. This review evaluates the literature assessing the safety and efficacy of DOACs in patients with various hypercoagulable disorders.. The current body of evidence supports the use of select DOACs for the treatment of CAT. In contrast, DOAC use in patients with APS and hereditary thrombophilia should be avoided at this time.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Rivaroxaban; Thrombophilia; Venous Thromboembolism

Anticoagulants are essential in the prevention of venous thromboembolism. However, the effectiveness and safety of different anticoagulants have always been controversial. Therefore, we aimed to expand the sample of anticoagulant results and rank the efficacy and safety of 19 anticoagulants in the prevention of venous thromboembolism when total knee or total hip arthroplasty procedure is performed.. A systematic review and network meta-analysis of randomized trials of adult patients undergoing total hip or knee arthroplasty were conducted. The trials were identified from PubMed, Web of Science, Cochrane Library, and Embase databases, in which anticoagulants were used as interventions randomized controlled trial. The incidence of venous embolism and bleeding are the key outcomes of assessing the efficacy of intervention drugs. We used the Physical Therapy Evidence Database (PEDro) to assess risk bias and used pairwise comparison and network meta-analysis with random effects to estimate the summary relative risk. The study has been registered with PROSPERO, number CRD42020200747.. From the 4083 identified manuscripts, 45,067 participants from 53 randomized trials were included in the analysis and randomly assigned to 19 anticoagulants. With Enoxaparin as a control, Rivaroxaban (risk difference 0.07, 95 % credible interval 0.06 to 0.08), Edoxaban (RD 0.09, 95 % CrI 0.08 to 0.11), and Apixaban (RD 0.05, 95 % CrI 0.04 to 0.06) had the best effect in preventing VTE. However, in terms of comprehensive bleeding rate, Apixaban, Edoxaban, and Darexaban were the most effective and stable. Although effective in preventing VTE, bleeding remains relatively high in Rivaroxaban. Enoxaparin is low-molecular-weight heparin that is widely used in clinics, and although its overall efficacy is not the best, its efficacy and safety are very stable.. According to the available data, Apixaban, Edoxaban, and Darexaban are better than any anticoagulants in the prevention of VTE and bleeding during total knee or total hip arthroplasty. In our study, Fondaparinux, Eribaxaban, Dalteparin, Betrixaban, Bemiparin, Reviparin, Acenocoumarol, and Tinzaparin were scarce in the included studies, therefore, more evidence is needed to prove their efficacy and safety.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism

Venous thromboembolism (VTE) is the leading preventable cause of death in hospitalized patients and data consistently show that acutely ill medical patients remain at increased risk for VTE-related morbidity and mortality in the post-hospital discharge period. Prescribing extended thromboprophylaxis for up to 45 days following an acute hospitalization in key patient subgroups that include more than one-quarter of hospitalized medically-ill patients represents a paradigm shift in the way hospital-based physicians think about VTE prevention. Advances in the field of primary thromboprophylaxis in acutely-ill medical patients using validated VTE and bleeding risk assessment models have established key patient subgroups at high risk of VTE and low risk of bleeding that may benefit from both in-hospital and extended thromboprophylaxis. The direct oral anticoagulants betrixaban and rivaroxaban are now U.S. Food and Drug Administration-approved for in-hospital and extended thromboprophylaxis in medically ill patients and provide net clinical benefit in these key subgroups. Coronavirus disease-2019 may predispose patients to VTE due to excessive inflammation, platelet activation, endothelial dysfunction, and hemostasis. The optimum preventive strategy for these patients requires further investigation. This article aims to review the latest concepts in predicting and preventing VTE and discuss the new era of extended thromboprophylaxis in hospitalized medically ill patients.

Topics: Anticoagulants; Benzamides; COVID-19; Critical Care; Decision Support Systems, Clinical; Duration of Therapy; Hospitalization; Humans; Medical Informatics; Patient Discharge; Pulmonary Embolism; Pyridines; Risk Assessment; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism; Venous Thrombosis

This review describes and analyzes literature to provide recommendations for use of extended-duration thromboprophylaxis (EDT) in medically ill patients.. Guidelines recommend pharmacologic thromboprophylaxis for patients at increased thrombosis risk during hospitalization and recommend against extending thromboprophylaxis beyond hospitalization. Despite these recommendations, observational data demonstrate that venous thromboembolism (VTE) risk persists following hospital discharge. A MEDLINE literature search was performed to identify original research evaluating the safety and efficacy of EDT. Eight meta-analyses and 5 randomized controlled trials-each varying in the agents studied (enoxaparin, rivaroxaban, apixaban, and betrixaban)-were selected for inclusion. Collectively, the evaluated data demonstrates that EDT reduces the incidence of VTE at the expense of increasing the risk of major bleeding and without providing mortality reduction. Variations in enrollment criteria, differences in EDT strategies, and uncertainty regarding proper patient selection limit the applicability of EDT in practice. Rivaroxaban and betrixaban gained Food and Drug Administration (FDA) approval on the basis of results of the APEX and MARINER trials and a post hoc analysis of the MAGELLEN trial results. Although a number of agents are FDA approved for use in EDT, clinicians must carefully weigh the risks vs benefits of EDT with these agents until studies demonstrate a more favorable risk-benefit profile.. Evidence to support EDT in medically ill patients is inconclusive and has highlighted the need for an individualized approach. The reviewed evidence supports guideline recommendations from both the American College of Chest Physicians and the American Society of Hematology that recommend against routine use of EDT in the majority of medically ill patients. Future studies are needed to optimize the risk-benefit profile of EDT and to ensure proper patient selection.

Topics: Anticoagulants; Enoxaparin; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism

To evaluates the efficacy and safety of rivaroxaban versus aspirin in prevention of venous thromboembolism (VTE) following total hip (THA) or knee arthroplasty (TKA) or hip fracture surgery.. Major databases were systematically searched for all relevant studies published in English up to October 2020. The meta-analysis was conducted using RevMan 5.3 software.. In total, 7 studies were retrieved which contained 5133 patients. Among these patients, 2605 patients (50.8%) received rivaroxaban, whereas 2528 patients (49.2%) received aspirin. There were no statistical difference between aspirin and rivaroxaban for reducing VTE (RR = 0.75, 95% CI 0.50-1.11, I. There was no significant difference between aspirin and rivaroxaban in prevention of venous thromboembolism following total joint arthroplasty or hip fracture surgery. Aspirin may be an effective, safe, convenient, and cheap alternative for prevention of VTE. Further large randomized studies are required to confirm these findings.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Female; Fracture Fixation, Internal; Hip Fractures; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Antithrombotic therapies are associated with an increased bleeding risk. Abnormal uterine bleeding data have been reported in clinical trials of patients with venous thromboembolism (VTE), but data are limited for patients with atrial fibrillation (AF).. Using real-world data from four US healthcare databases (October 2010 to December 2018), we compared the occurrence of severe uterine bleeding among women newly exposed to rivaroxaban, apixaban, dabigatran, and warfarin stratified by indication.. To reduce potential confounding, patients in comparative cohorts were matched on propensity scores. Treatment effect estimates were generated using Cox proportional hazard models for each indication, in each database, and only for pairwise comparisons that met a priori study diagnostics. If estimates were homogeneous (I. Data from 363,919 women newly exposed to a direct oral anticoagulant or warfarin with a prior diagnosis of AF (60.8%) or VTE (39.2%) were analyzed. Overall incidence of severe uterine bleeding was low in the populations exposed to direct oral anticoagulants, although relatively higher in the younger VTE population vs the AF population (unadjusted incidence rates: 2.8-33.7 vs 1.9-10.0 events/1000 person-years). In the propensity score-matched AF population, a suggestive, moderately increased risk of severe uterine bleeding was observed for rivaroxaban relative to warfarin [hazard ratios and 95% confidence intervals from 0.83 (0.27-2.48) to 2.84 (1.32-6.23) across databases with significant heterogeneity], apixaban [pooled hazard ratio 1.45 (0.91-2.28)], and dabigatran [2.12 (1.01-4.43)], which were sensitive to the time-at-risk period. In the propensity score-matched VTE population, a consistent increased risk of severe uterine bleeding was observed for rivaroxaban relative to warfarin [2.03 (1.19-3.27)] and apixaban [2.25 (1.45-3.41)], which were insensitive to the time-at-risk period.. For women who need antithrombotic therapy, personalized management strategies with careful evaluation of benefits and risks are required. CLINICALTRIALS.. NCT04394234; registered in May 2020.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Observational Studies as Topic; Pyridones; Risk Assessment; Rivaroxaban; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE), which is characterized by pulmonary embolism and deep vein thrombosis, has become a serious public concern. Notably, over half of the patients with VTE are over 70 years of age, but elderly patients are at high risk of anti-coagulation and bleeding, which increase with age. Moreover, risk factors and frailty also show a difference between elderly patients and ordinary patients diagnosed with VTE. Rivaroxaban is a direct inhibitor of activated factor Xa and has the advantage of predictable pharmacodynamics and pharmacokinetics, no coagulation monitoring, and few drug interactions. As a first-line therapy for VTE, this drug is more advantageous than traditional therapy and exhibits good efficacy and safety for ordinary patients. However, the effectiveness and safety of rivaroxaban in elderly patients have not been fully elucidated. This article reviewed the use of rivaroxaban in elderly patients, including drug interactions, monitoring, reversal agents of rivaroxaban, and the use of small dosages of rivaroxaban in elderly patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for stroke prevention in atrial fibrillation (AF) and the treatment and prevention of venous thromboembolism. There is an issue with safety, especially in clinically relevant bleeding. We performed a network meta-analysis to evaluate the risk of major gastrointestinal (GI) bleeding associated with NOACs.. Interventions were warfarin, enoxaparin, apixaban, dabigatran, edoxaban, and rivaroxaban. The primary outcome was the incidence of major GI bleeding. A subgroup analysis was performed according to the following indications: AF, deep venous thrombosis/pulmonary embolism, and postsurgical prophylaxis.. A total of 29 randomized controlled trials (RCTs) and 4 large observation population studies were included. Compared with warfarin, apixaban showed a decreased the risk of major GI bleeding (relative risk [RR] 0.54, 95% confidence interval [CI] 0.25-0.76), and rivaroxaban tended to increase this risk (RR 1.40, 95% CI 1.06-1.85). Dabigatran (RR 1.25, 95% CI 0.98-1.60), edoxaban (RR 1.07, 95% CI 0.69-1.65), and enoxaparin (RR 1.24, 95% CI 0.63-2.43) did not significantly increase the risk of GI bleeding than did warfarin. In the subgroup analysis, according to indications, apixaban showed a decreased risk of major GI bleeding (RR 0.50, 95% CI 0.34-0.74) than did warfarin in AF studies. Dabigatran (RR 2.36, 95% CI 1.55-3.60, and rivaroxaban (RR 1.75, 95% CI 1.10-6.41) increased the risk of major GI bleeding than did apixaban. An analysis of studies on venous thromboembolism or pulmonary embolism showed that no individual NOAC or enoxaparin was associated with an increased risk of major GI bleeding compared to warfarin.. Individual NOACs had varying profiles of GI bleeding risk. Results of analyses including only RCTs and those including both RCTs and population studies showed similar trends, but also showed several differences.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Enoxaparin; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Network Meta-Analysis; Observational Studies as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Due to the high risk of ischemic and arterial or venous bleeding events in atrial fibrillation (AF) or venous thromboembolism (VTE) patients with renal impairment (RI), selection of appropriate anticoagulant regimen is important. Therefore, we systematically reviewed and compared the safety and effects of oral anticoagulants in AF and VTE patients with RI.. Eligible articles were identified through a literature search in PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library for studies published between January 2008 and November 2020. Network meta-analysis was conducted with STATA 14.0 to analyze the effects and safety of each drug with regard to different levels of renal function.. 15 studies including 82,931 patients (76,957 with AF and 5974 with VTE) were analyzed. Compared with those of warfarin, the risk ratios of effect and safety outcomes of apixaban were 0.70 (95% confidence interval [CI] 0.60-0.82) and 0.56 (95% CI 0.42-0.76) in AF patients and 0.33 (95% CI 0.19-0.59) and 0.95 (95% CI 0.68-1.34) in VTE patients. Apixaban had the first or second highest probability of being ranked first with respect to surface under the cumulative ranking curve (SUCRA) scores in the prevention of major bleeding events, while in the prevention of ischemic events, rivaroxaban showed a higher SUCRA score (0.78-0.92) in mild RI patients and dabigatran showed a higher SUCRA value (0.90-0.99) in moderate RI patients.. In the systematic review and meta-analysis, for AF or VTE patients with RI, direct oral anticoagulants performed comparably to or better than warfarin with regard to safety and effects. The network meta-analysis indicated that for patients with mild RI, apixaban might be safer for patients with a lower risk of ischemic events, while rivaroxaban might be suitable for patients with a lower risk of bleeding events. For patients with moderate RI, apixaban could reduce the risk of ischemic events without increasing the risk of bleeding events. For AF patients with severe RI, apixaban, rivaroxaban, and warfarin showed a similar effect. These results might provide suggestions for clinical arterial and venous thrombosis prevention.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Network Meta-Analysis; Renal Insufficiency; Rivaroxaban; Venous Thromboembolism; Warfarin

The main purpose of prescribing oral anticoagulants in patients undergoing total knee and total hip replacement surgery is to prevent venous thromboembolism (VTE). The present study aimed to summarize evidence from economic evaluations regarding new oral anticoagulants (NOACs) used in VTE prophylaxis after joint replacement surgery.. To obtain relevant literature on economic evaluations of NOACs used in the prevention of VTE following joint replacement surgery, we searched the Cochrane Library, PubMed, Web of Science, Embase, and Scopus, as well as specialized economic evaluation databases, for articles published from January 2008 to December 2019. Next, 2 reviewers screened the titles and abstracts of studies, extracted data from the full-text articles, and assessed the quality of the methodologies using the Quality of Health Economic Studies checklist.. Twenty-eight studies of economic evaluations met the inclusion criteria of the research. The quality assessment showed that 20 articles had scores within the range of 75 to 100 (high quality), and 9 studies had scores within the range of 50 to 74 (moderate quality). All of the identified studies had been carried out based on modelling, and 23 studies used decision trees to model acute events after surgery. In addition, 20 studies utilized a Markov model to capture long-term complications of VTE. The results showed that rivaroxaban was more cost-effective than apixaban and dabigatran from a perspective of the health care system in the prevention of VTE after total knee and total hip replacement surgery. In addition, apixaban was associated with a lower risk for bleeding events than other NOACs, making it the most cost-effective NOAC from the perspective of the payer.. The results suggest that NOACs are cost-effective alternatives to low-molecular-weight heparins. Rivaroxaban and dabigatran were assessed as the most and least cost-effective prophylaxis options, respectively, after joint replacement surgery for the prevention of VTE. It is recommended that future research be conducted on economic evaluations of edoxaban.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Cost-Benefit Analysis; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Administration, Oral; Adult; Anticoagulants; Child; Heparin; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Venous Thromboembolism

Traditionally, venous thromboembolism (VTE) resulting from major transient risk factors (e.g., surgery or trauma) or a major persistent risk factor such as cancer, has been defined as being provoked, whereas unprovoked VTE encompasses events without an identifiable cause. These categorizations influence anticoagulant treatment duration; unlike VTE provoked by major transient risk factors, extended anticoagulation beyond 3 months is advised for patients with cancer or unprovoked VTE due to risk persistence after treatment cessation. However, some patients with VTE provoked by minor transient or minor persistent risk factors may also be candidates for extended anticoagulation therapy due to the continuing risk of recurrence. In patients who require extended therapy, vitamin K antagonists (VKAs) are effective but are associated with an increased risk of bleeding and various treatment burdens (e.g., anticoagulation monitoring and dose adjustment). Evaluations of extended VTE treatment with the less-burdensome direct oral anticoagulants such as apixaban, dabigatran, edoxaban, and rivaroxaban show that they are at least as safe and effective as VKAs in a broad range of patients. In addition, apixaban and rivaroxaban offer more than one dosing option, allowing tailoring of treatment to the patient's specific risk factor profile. Analysis of more granular definitions for risk factor groupings has also yielded vital information on the most appropriate strategies for the treatment of patients with specific risk factors, highlighting that extended anticoagulation treatment may benefit those with minor transient and persistent environmental and nonenvironmental risk factors who commonly receive shorter-duration therapy.

Topics: Aged; Anticoagulants; Humans; Patient Selection; Precision Medicine; Pyrazoles; Pyridones; Renal Insufficiency; Risk Factors; Rivaroxaban; Venous Thromboembolism; Vitamin K; Withholding Treatment

Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the anticoagulant effects, potential anti-tumor effects of DOACs have also been studied in animal cancer models. In this study, we summarize the effects of DOACs on cancer growth and metastasis in animal models through a systematic review with a qualitative analysis.. PubMed, EMBASE and Web of Science were systematically searched for original studies that describe animal models of cancer in which one of the experimental groups received DOAC monotherapy, and which reported quantitatively on primary tumor or metastases.. Nine studies - reporting a total of 19 animal experiments - met the inclusion criteria. These 19 experiments included spontaneous cancer (n = 2), carcinogenicity (n = 2), xenograft (n = 7) and syngeneic (n = 8) models, encompassing orthotopic (n = 7), subcutaneous (n = 5), intraperitoneal (n = 1) and intravenous (n = 2) injection of cancer cells and included treatments with the DOACs ximelagatran (n = 4), dabigatran etexilate (n = 6) and/or rivaroxaban (n = 11). DOAC treatment decreased tumor growth at implanted and metastatic site in 18.8% (3/16) and 20.0% (3/15) of the experiments, respectively. Conversely, DOACs increased tumor growth at implanted and metastatic site in 6.3% (1/16) and 20.0% (3/15) of the experiments, respectively.. DOAC monotherapy resulted in neoplastic changes in a rat carcinogenicity study, showed a lack of effect in mouse xenograft models, while the effect on cancer growth and metastasis in mouse syngeneic models depended on the timing of DOAC treatment and type of cancer model used.

Topics: Administration, Oral; Animals; Anticoagulants; Antithrombins; Dabigatran; Humans; Mice; Models, Animal; Neoplasms; Pyrazoles; Pyridones; Rats; Rivaroxaban; Venous Thromboembolism

Topics: Factor Xa Inhibitors; Hemorrhage; Humans; Incidence; Neoplasms; Rivaroxaban; Venous Thromboembolism

Direct oral anticoagulants, anti-IIa or anti-Xa, are widely used in the treatment and prevention of venous thromboembolic disease as well as in nonvalvular atrial fibrillation. Direct oral anticoagulants are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, theoretical drug interactions exist since direct oral anticoagulants are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway. Direct oral anticoagulants do not have a marketing authorization for the treatment of cancer-associated thrombosis unlike low-molecular-weight heparins which remain the gold standard treatment today. However, recent studies have compared low-molecular-weight heparins to direct oral anticoagulants in the treatment of cancer-associated thrombosis. Results of these studies showed a non-inferiority of direct oral anticoagulants in the prevention of recurrent thromboembolic events but at the cost of an increased hemorrhagic risk, in particular for patients with gastrointestinal and urogenital cancers. Thus, international guidelines, unlike French guidelines, integrate them in first line of the therapeutic strategy of cancer patients. We are certainly entering an era of personalized therapy for cancer-associated thrombosis, considering cancer type and also the theoretical risk of drug interactions with anti-cancer treatments or supportive care.

Topics: Anticoagulants; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Cytochrome P-450 Enzyme System; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasm Proteins; Neoplasms; Pyrazoles; Pyridines; Pyridones; Recurrence; Rivaroxaban; Secondary Prevention; Thiazoles; Thrombosis; Venous Thromboembolism

Venous thromboembolism (VTE) is a common complication among patients with cancer that is associated with significant morbidity, mortality and health care costs. There is a significant lack of awareness among health care providers and patients leading to delays in seeking medical attention or diagnosis when signs and symptoms of suspected VTE occur as well as underappreciation of potential benefits of different thromboprophylaxis options. Clinical prediction rules (e.g. Khorana risk score) can be used by clinicians to stratify patients according to their underlying risk of VTE. Low-molecular-weight-heparin and direct oral anticoagulants (rivaroxaban and apixaban) have been shown to be safe and effective thromboprophylactic options in this patient population. Health care providers should educate all patients regarding VTE and consider thromboprophylaxis in patients at higher risk of VTE complications. Decisions about thromboprophylaxis should be made with the patients and include a discussion about relative benefits and harms, costs and duration.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

To review the literature on treatment of venous thromboembolism (VTE) and prevention of cardioembolic stroke with direct-acting oral anticoagulants (DOACs) in low- and high-body-weight patients and to make recommendations regarding agent selection and dosing in these patient populations.. The selection and optimal dosing of DOACs in low- and high-body-weight patients has not yet been fully elucidated by clinical trials; however, evidence suggests that issues of both safety and efficacy in patients at the extremes of body weight may warrant careful consideration when selecting a DOAC for such patients. This review provides a thorough discussion of the use of DOACs in the treatment of VTE and prevention of cardioembolic stroke in patients at the extremes of body weight and provides guidance regarding agent selection.. While the published evidence on use of DOACs in patients at extremes of body weight is sparse, apixaban and rivaroxaban appear to have the most favorable safety and efficacy profiles. Edoxaban and dabigatran should be avoided.

Topics: Anticoagulants; Body Weight; Dabigatran; Drug Dosage Calculations; Factor Xa Inhibitors; Humans; Obesity; Overweight; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Four direct-acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years).. Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta-analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel-Haenszel relative risk (RR) random effects model was used to pool results across studies.. Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow-up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR = .56; 95% confidence interval [CI] = .38-.82). There was no statistically significant difference in the safety outcomes (RR = .77; 95% CI = .56-1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome.. In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE-related deaths compared with VKAs with similar bleeding outcomes.

Topics: Administration, Oral; Aged; Anticoagulants; Antifibrinolytic Agents; Antithrombins; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism; Vitamin K

Deep vein thrombosis (DVT) and pulmonary embolism (PE) together are called venous thromboembolism (VTE) and impose a high economic burden on healthcare systems. Thousands of people are hospitalized annually due to benign and treatable diseases but die due to PE; with the adoption of appropriate prevention, these deaths can be prevented.. To investigate the cost-effectiveness of using rivaroxaban versus enoxaparin in published economic analyses for prevention of VTE after total knee (TKR) or hip replacement (THR).. In a systematic review electronic searches were performed on various online databases, including PubMed, Web of science, Embase, Scopus, Health Economic Evaluations Database (HEED), and ProQuest. The inclusion criteria were: studies that were conducted on the cost-effectiveness of rivaroxaban versus enoxaparin for the prevention of VTE after TKR and THR; cost-effectiveness studies conducted using decision analysis models based on the economic evaluation approach; studies with available full-text papers; and studies written in English and published between 2007 and 2019. The exclusion criteria were: studies with partial cost effectiveness (such as effectiveness assessment, cost assessment, quality-of-life assessment); studies written in languages other than English; and all protocols, conference abstracts, and letters to the editor. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to qualitatively evaluate the studies.. Of a total of 537 initial studies, nine papers met the inclusion criteria. The time scope of studies ranged from 3 months to 5 years. Among the selected studies, some studies had included discount rates (n = 4) and the other studies did not utilize discount rates and were set to zero percent by default (n = 5). In all studies, direct medical costs, including costs related to the prevention, diagnosis, and treatment of VTE and PE, and management and monitoring of treatment costs were reviewed.. The results of this systematic review showed that using rivaroxaban in patients undergoing total knee or hip replacement reduced costs and increased quality of life. However, since most of the studies had been conducted in developed countries, it is not possible to generalize the results to developing countries. Nonetheless, given that rivaroxaban is administered orally and does not require continuous monitoring, it will be less costly for patients and health systems and is more appropriate to administer it as a thromboprophylactic drug following total knee or hip replacement surgery.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Enoxaparin; Humans; Middle Aged; Quality of Life; Rivaroxaban; Venous Thromboembolism

The paper is a narrative review of the literature on the use of direct oral anticoagulants (DOACs) for the VTE treatment in challenging patients: senile age (≥75 years), impaired renal function (estimated glomerular filtration rate ≤50 ml/min), fragility (one of the previous characteristics and/or bodyweight ≤50 kg). The paper discusses the studies of EINSTEIN DVT and PE (rivaroxaban), AMPLIFY (apixaban), HOKUSAI-VTE (edoxaban), RE-COVER I and II (dabigatran) in the focus of the secondary analysis in the pre-specified patient's subgroups, as well as their pooled analyzes and meta-analyzes. Based on the results of this review, it was concluded that in a subgroup of senile age patients, dabigatran increases the risk of major bleeding by 4.8 times and has no advantages over vitamin K antagonists (VKA); rivaroxaban and apixaban retain superiority over VKA on the safety outcomes and reduce the risk of major bleeding by 73% and 77%. In the subgroup of patients with impaired renal function, the use of apixaban and dabigatran is associated with an increase in the risk of major bleeding by 6.5 and 7.3 times, and these DOACs do not have advantages over VKA; rivaroxaban retains its superiority over VKA and reduces the risk of major bleeding by 78%. For fragile patients, a secondary analysis is available only for rivaroxaban, which remains superior to VKA on safety endpoints and reduces the risk of major bleeding by 73%. In the absence of direct comparisons between the available DOACs, the presented data can be used as a rational approach for the choice of appropriate treatment for VTE in challenging patients.. Представлен классический описательный обзор литературы, посвященный проблемам использования прямых оральных антикоагулянтов (ПОАК) для лечения венозных тромбоэмболических осложнений (ВТЭО) у ослабленных пациентов: лиц старческого возраста (≥75 лет), пациентов с нарушенной функцией почек (СКФ ≤50 мл/мин), а также «хрупких» больных, имеющих один или оба из перечисленных признаков наряду с низкой массой тела (≤50 кг). Обсуждаются известные исследования EINSTEIN DVT и PE (ривароксабан), AMPLIFY (апиксабан), HOKUSAI-VTE (эдоксабан), RE-COVER I и II (дабигатран) в фокусе вторичного анализа результатов в искомых подгруппах пациентов, а также работы, объединившие их результаты, и метаанализы. Сделаны выводы, что у больных старческого возраста дабигатран увеличивает риск развития больших кровотечений в 4,8 раза и не имеет преимуществ перед антагонистами витамина К (АВК); ривароксабан и апиксабан сохраняют превосходство над АВК с позиции безопасности и снижают угрозу больших кровотечений на 73 и 77%. У пациентов с нарушенной функцией почек использование апиксабана и дабигатрана ассоциируется с увеличением риска больших кровотечений в 6,5 и 7,3 раза, названные ПОАК не имеют преимуществ перед АВК; ривароксабан сохраняется свое превосходство над АВК и снижает угрозу большого кровотечения на 78%. Для подгруппы «хрупких» пациентов вторичный анализ доступен только для ривароксабана, который сохраняется свое превосходство над АВК с позиции безопасности и снижает риск развития больших кровотечений на 73%. В отсутствие прямых сравнений между доступными ПОАК представленные данные могут использоваться с целью обеспечения рационального подхода к выбору препарата для антикоагулянтной терапии ВТЭО у ослабленных пациентов.

Topics: Administration, Oral; Age Factors; Aged; Antithrombins; Dabigatran; Frail Elderly; Humans; Pyrazoles; Pyridones; Renal Insufficiency; Rivaroxaban; Venous Thromboembolism

Venous thromboembolism (VTE) is often cited as a major cause of death and morbidity in cancer patients. Even a non-lethal VTE causes distress and is commonly perceived by patients as a set-back in the cancer journey and a threat to the cancer treatment. It is also known that the risk of VTE varies between cancers (cancer-related risk factors), between patients (patient-related risk factors), and also within the cancer journey of a single patient. Risk can increase during treatments like surgery and chemotherapy and decline during remission. Neither the low molecular weight heparins nor the vitamin K analogues have gained an established role in thromboprevention guidance other than in 'the high risk' patient, who remains a rather ambiguous entity. The recently published randomised studies of rivaroxaban and apixaban in moderate- to high-risk thrombosis patients, assigned by the Khorana Risk Score, has seen the inclusion of direct oral anticoagulants (DOACs) in recent guidelines (e.g. the American Society of Clinical Oncology 2019 guidelines) for this indication. The ease of administration and the demonstrated greater patient adherence to oral agents has heightened the expectation that a practice-changing thromboprevention study in cancer patients should be realizable. However, key unmet needs that pose familiar challenges remain and as yet do not have satisfactory solutions. Anticoagulants carry risks of bleeding that are higher in the cancer population. There is therefore the challenge of sufficient risk reduction of VTE from the intervention balanced against the number of patients that may be harmed from bleeding. There is also the challenge of penetrating the risk threshold beyond which oncologists would deem thromboprevention a clinically meaningful praxis. Thus, identifying the high-risk groups of patients or targeting the length or timing of the thromboprevention to when the risks are highest are major questions that remain the subject of ongoing research. Notably all this is taking place against a backdrop of changing therapeutics for many cancers (e.g. targeted agents, checkpoint inhibitors and combinations) and their assorted impact on VTE incidence. In this review, past data for the ambulatory cancer patient are summarised, the latest evidence for the direct oral anticoagulants apixaban and rivaroxaban are analysed and the challenges of identifying the high-risk patients that have the greater chance of benefiting from thromboprophylaxis are discu

Topics: Administration, Oral; Anticoagulants; Humans; Medical Oncology; Neoplasms; Rivaroxaban; Venous Thromboembolism

There are many anticoagulant test indexes available for direct oral anticoagulants (DOACs), but how to select the appropriate index and the index cutoff values are still controversial. This is the first study, to our knowledge, to assess the association of different coagulation indicators with clinical outcomes among DOACs using a meta-analysis of observational studies.. A medical literature search was conducted using PubMed, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Library from inception to February 2020. Studies that reported relationships between coagulation indexes and clinical outcomes or the diagnostic value of coagulation assays were included in the analysis.. A total of 17 articles (7 meta-analyses and 10 systematic reviews) from 8904 citations were included in the analysis. In the analysis of bleeding events with coagulation indexes for DOACs, for peak prothrombin time level (cutoff value of 19-25 s), the pooled results found a sensitivity of 0.61 (95% CI, 0.44-0.75) and a specificity of 0.71 (95% CI, 0.49-0.86). For rivaroxaban, the trough anti-factor Xa concentration (AXA-C) (cutoff value of 400-500 ng/mL) had a sensitivity of 0.53 (95% CI, 0.16-0.87) and a specificity of 0.87 (95% CI, 0.71-0.94), with a diagnostic odds ratio of 7 (95% CI, 2-32). For apixaban, trough AXA-C had a sensitivity of 0.85 (95% CI, 0.60-0.96) and a specificity of 0.83 (95% CI, 0.52-0.95). The AUC of the AXA-C peak was higher than that of the trough AXA-C for apixaban, with a higher sensitivity and specificity. Compared with trough concentration of anti-factor IIa for dabigatran, the peak concentration had a higher specificity (98%) at the cutoff value of 484 ng/mL. In the analysis of thromboembolic events with coagulation indexes for DOACs, peak and trough prothrombin time values were not typically correlated with subsequent symptomatic venous thromboembolism, without a sensitivity or specificity higher than 90%. Trough AXA-C had a sensitivity of 100% and but a low specificity (<50%) for rivaroxaban-apixaban. Trough AXA-C had a sensitivity of 100% and a specificity of 32% with a cutoff value of 108 ng/mL for dabigatran.. Peak prothrombin time (19-25 s) and AXA-C had a better predictive value on bleeding outcomes for rivaroxaban and apixaban, whereas peak concentration of anti-factor IIa activity can be an indicator for dabigatran. Coagulation indexes might not be a good indicator of thromboembolic events of DOACs. Because the limited studies focused on association of coagulation indicators and clinical outcomes, more studies are needed to verify this in the future.

Topics: Administration, Oral; Blood Coagulation; Blood Coagulation Tests; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Prothrombin Time; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Cancer-associated venous thromboembolism remains an important but challenging aspect in the treatment of patients with cancer. Recently, alternatives to injection of low-molecular-weight heparin (LMWH) have been introduced, the non-vitamin K antagonist oral anticoagulants (NOACs), which could potentially alleviate patients from burdensome daily injections.. This review discusses the available evidence exploring the role of NOACs in the treatment and secondary prevention of cancer-associated venous thromboembolism, from randomized trials, observational data, contemporary guideline recommendations, and patient perspectives.. Edoxaban, rivaroxaban, and apixaban have proven attractive alternatives to LMWH for the treatment of cancer-associated venous thromboembolism. Contemporary guidelines have promptly endorsed the use of NOACs in patients with most cancer types. Nonetheless, issues remain regarding bleeding risk, interactions with medical cancer treatment, and the effectiveness and safety for extended treatment periods. There are head-to-head comparisons of the NOACs, and therefore no data favoring the use of one NOAC over the others. Patient's preferences are highly diverse and should be part of routine considerations when weighing risks and benefits associated with various available anticoagulant drugs.

Topics: Administration, Oral; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism

Anticoagulant therapy is in use for both prevention and treatment of venous and arterial thromboembolic disorders. Delivering safe and effective anticoagulation in the pediatric population is challenging, since the available standard therapy with parenteral UFH and LMWH is troublesome for most pediatric patients, and VKAs require frequent INR monitoring due to the unpredictable pharmacokinetics and numerous food and drug interactions. Rivaroxaban, a direct FXa inhibitor, offers the convenience of oral administration and predictable pharmacokinetics across a wide range of patients. Its safety and efficacy have been previously established in various adult indications.. This review outlines pharmacologic and clinical aspects regarding rivaroxaban treatment in adults and children, and provides a broad appraisal of the The EINSTEIN-Jr program which evaluated the safety and efficacy of body-weight adjusted pediatric rivaroxaban regimens for the treatment of VTE in children. A review of the literature using the keywords rivaroxaban and pediatric venous thromboembolism was conducted within the National Center for Biotechnology (NCBI) and EMBASE databases.. Rivaroxaban represents an appealing therapeutic alternative for VTE in children. Further research should explore additional indications for rivaroxaban in the pediatric population beyond that of VTE.

Topics: Administration, Oral; Anticoagulants; Child; Drug Interactions; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Venous Thromboembolism

Patients with cancer are at high risk of venous thromboembolic events, and this risk can be further increased in patients with certain cancer types and by cancer treatments. Guidelines on the prevention of cancer-associated thrombosis (CAT) recommend thromboprophylaxis for hospitalised patients; however, this is not routinely recommended for ambulatory patients receiving chemotherapy and is limited to specified high-risk patients. Identification of the ambulatory patients at risk of CAT who would most benefit from anticoagulant therapy is therefore critical to reduce the incidence of this complication. For patients receiving thromboprophylaxis for CAT, treatment options include low molecular weight heparin, acetylsalicylic acid, warfarin or direct oral anticoagulants (apixaban or rivaroxaban), dependent on the cancer type and cancer treatment regimen. This review discusses emerging clinical trial data and their potential clinical impact.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism; Warfarin

Currently licenced direct oral anticoagulants selectively target thrombin (eg, dabigatran) or coagulation factor Xa (eg, apixaban, betrixaban, edoxaban, and rivaroxaban). Designed to be given in fixed doses without routine monitoring, direct oral anticoagulants have a lower propensity for food and drug interactions than do vitamin K antagonists, and in randomised controlled trials involving around 250 000 patients, they were at least as effective for prevention and treatment of thrombosis and were associated with a lower risk of life-threatening bleeding. The absolute benefits of direct oral anticoagulants over vitamin K antagonists are modest; however, guidelines recommend them in preference to vitamin K antagonists for most indications because of their ease of use and superior safety. The greatest benefits of direct oral anticoagulants are likely to be in patients who were previously deemed unsuitable for vitamin K antagonist therapy. The emergence of generic preparations is expected to further increase the uptake of direct oral anticoagulants, particularly in countries where they are currently not widely used because of cost. Direct oral anticoagulants are contraindicated in patients with mechanical heart valves and should be used with caution or avoided in patients with advanced kidney or liver disease. In this Therapeutics paper, we review the pharmacology of direct oral anticoagulants, summarise the evidence that led to their approval and incorporation into treatment guidelines, and explore key unresolved issues. We also briefly discuss future perspectives for the development of oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

Heavy menstrual bleeding (HMB) is a common complication of anticoagulation, affecting ∼70% of menstruating women receiving oral anticoagulants. The risk of HMB is lower with apixaban and/or dabigatran than with rivaroxaban. HMB can result in iron deficiency with or without anemia, increased need for medical interventions, decreased quality of life, and missed school/work. Mainstays of treatment include hormone therapies such as the levonorgestrel intrauterine system, subdermal implant, and other progesterone-based therapies, which can result in decreased blood loss and, in some cases, amenorrhea. Combined hormone therapies can be used while patients continue receiving anticoagulation and are also highly effective for decreasing menstrual blood loss. Rarely, procedure-based interventions such as endometrial ablation may be required. Patients should be evaluated for iron deficiency and anemia and offered supportive therapies as needed. Abbreviating the course of anticoagulation or skipping doses can increase the risk of recurrent venous thromboembolism by as much as fivefold, but switching oral anticoagulants may be considered. Awareness of HMB and careful history taking at each visit are crucial to avoid a missed diagnosis.

Topics: Adult; Anticoagulants; Female; Humans; Levonorgestrel; Menorrhagia; Pyrazoles; Pyridones; Quality of Life; Rivaroxaban; Venous Thromboembolism

Venous thrombotic events frequently complicate major elective arthroplasties such as hip and knee replacements. The risk of proximal deep vein thrombosis and pulmonary embolism is estimated at 5 %. For decades, the use of low-dose heparins for up to 5 weeks post-surgery has helped to reduce the risk of thrombotic complications. In this narrative review, we describe the evidence supporting the use of direct oral anticoagulants (in Switzerland - rivaroxaban and apixaban), whose risk-benefit ratios appears superior to that of heparins, at a lower cost. Hybrid strategies combining a short-term anticoagulant followed by low-dose aspirin are also recommended for patients deemed at low thrombotic risk.. Les thromboses veineuses profondes proximales et les embolies pulmonaires sont des complications redoutées après des interventions électives majeures en chirurgie orthopédique (prothèses totales de la hanche et du genou), avec une incidence cumulée estimée à 5 %. Depuis des décennies, ce risque est réduit par l’utilisation d’héparine à dose préventive jusqu’à 5 semaines postopératoires. Dans cette revue narrative, nous décrivons les évidences motivant l’utilisation des anticoagulants oraux directs (rivaroxaban et apixaban en Suisse) qui semblent présenter un rapport bénéfice-risque supérieur aux héparines, à un coût moindre. Des stratégies hybrides comprenant un anticoagulant puis l’aspirine sont désormais également recommandées chez des patients considérés à bas risque thrombotique.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Heparin; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

The risk of recurrence of venous thromboembolism (VTE) persists after interruption of the initial anticoagulation therapy. New evidence shows that direct oral anticoagulants are effective for extended treatment of VTE and may reduce the risk of all-cause mortality. The optimal duration of anticoagulation after VTE is, however, controversial and complicated by the need for individualised assessment and balance between thrombosis and bleeding risks. Three direct oral anticoagulants (rivaroxaban, apixaban and dabigatran) have been studied for extended treatment of VTE. Dabigatran was shown to be safer than vitamin K antagonists and similarly effective for the prevention of recurrent VTE. Dabigatran, apixaban and rivaroxaban resulted in significant decreases in the rate of recurrent symptomatic VTE when compared to placebo, without a statistically significant difference in the risk of major bleeding. The latest guidelines of the American College of Chest Physicians suggest the use of low-dose aspirin to prevent VTE recurrence in patients who want to stop anticoagulation. In the randomised, double-blind, phase 3 EINSTEIN CHOICE trial, once-daily rivaroxaban at doses of 20 mg or 10 mg and 100 mg of aspirin were compared in VTE patients for whom there was clinical equipoise for extended anticoagulation. Either a treatment dose (20 mg) or a prophylactic dose (10 mg) of rivaroxaban significantly reduced the risk of VTE recurrence without a significant increase in bleeding risk compared with aspirin. The EINSTEIN CHOICE trial included patients with provoked or unprovoked VTE. Patients with VTE provoked by minor persistent or minor transient risk factors enrolled in this trial had not-negligible VTE recurrence rates. These new findings on extended therapy suggest the possibility of anticoagulation regimens at intensities tailored to the patients' risk profiles and VTE characteristics, with a shift of the risk-benefit balance in favour of extended treatment.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Dabigatran; Glycosaminoglycans; Hemorrhage; Humans; Middle Aged; Pyrazoles; Pyridones; Recurrence; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Vitamin K

Both apixaban and rivaroxaban have been approved for use in acute venous thromboembolism (VTE). Although indirect comparison through network meta-analyses of randomized trials have been performed to compare the efficacy and safety of these agents, further comparison between these agents was lacking until recently. We sought to systematically review and carry out a meta-analysis of studies to further compare apixaban with rivaroxaban from multiple studies done in the real-world settings. Studies comparing rivaroxaban with apixaban in patients with acute VTE were identified through electronic literature searches of MEDLINE, EMBASE, Scopus, and the Cochrane library up to May 2019. Study-specific risk ratios (RRs) were calculated and combined using a random-effects model meta-analysis. In an analysis involving 24 041 patients, recurrent VTE within 6 months occurred in 56 of 4897 patients (1.14%) in the apixaban group and 258 of 19 144 patients (1.35%) in the rivaroxaban group (RR, 0.89; 95% confidence interval [CI], 0.67-1.19;

Topics: Blood Coagulation; Hemorrhage; Humans; Odds Ratio; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

To assess the efficacy and safety of venous thromboembolism prophylaxis in people undergoing elective total hip replacement.. Systematic review and Bayesian network meta-analyses of randomized controlled trials were conducted for 3 outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding (MB). MEDLINE, EMBASE, and Cochrane Library (CENTRAL) databases were searched. Study quality was assessed using the Cochrane risk-of-bias checklist. Fixed- and random-effects models were fitted and compared. The median relative risk (RR) and odds ratio (OR) compared with no prophylaxis, with their 95% credible intervals (CrIs), rank, and probability of being the best, were calculated.. Forty-two (n = 24 374, 26 interventions), 30 (n = 28 842, 23 interventions), and 24 (n = 31 792, 15 interventions) randomized controlled trials were included in the DVT, PE, and MB networks, respectively. Rivaroxaban had the highest probability of being the most effective intervention for DVT (RR 0.06 [95% CrI 0.01-0.29]). Strategy of low-molecular-weight heparin followed by aspirin had the highest probability of reducing the risk of PE and MB (RR 0.0011 [95% CrI 0.00-0.096] and OR 0.37 [95% CrI 0.00-26.96], respectively). The ranking of efficacy estimates across the 3 networks, particularly PE and MB, had very wide CrIs, indicating high degree of uncertainty.. A strategy of low-molecular-weight heparin given for 10 days followed by aspirin for 28 days had the best benefit-risk balance, with the highest probability of being the best on the basis of the results of the PE and MB network meta-analyses. Nevertheless, there is considerable uncertainty around the median ranks of the interventions.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Bayes Theorem; Cost-Benefit Analysis; Elective Surgical Procedures; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Patient Preference; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Venous Thromboembolism

The application of venous thromboembolism (VTE) prophylaxis has been the topic of intense debate in plastic surgery. The overall incidence of VTE is low in plastic surgery patients as compared to other surgical subspecialties but may be higher in the inpatient rather than outpatient plastic surgery populations. The Caprini Risk Assessment Model is the most highly studied and validated tool to assess VTE risk in plastic surgery patients. However, the Caprini model lacks procedure-specific risk assessment and patient-specific risk factor calculations. Due to these limitations, such as the low incidence and the heterogeneous nature of the specialty, trials lacked the power to capture proof of benefit, except in the highest-risk inpatient population. The emerging use of aspirin and novel oral anticoagulants may provide an alternative, as noninferiority in terms of efficacy and safety has been demonstrated in other fields. In this review, the authors intend to summarize the current state of evidence for prevention and explore the modalities available for prophylaxis, including novel oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Aspirin; Chemoprevention; Heparin, Low-Molecular-Weight; Humans; Incidence; Plastic Surgery Procedures; Postoperative Complications; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Venous Thromboembolism

The use of direct oral anticoagulants (DOACs) has been largely -implemented in the management of venous thromboembolic disease in non-cancer patients. In cancer-associated thrombosis, low molecular weight heparins (LMWHs) and especially dalteparin have long been the reference standard therapy. Following the publication of two randomised trials comparing edoxaban and rivaroxaban to -dalteparin, DOACs now represent an alternative with an interesting efficacy and safety profile. Moreover, they offer the comfort of an oral administration and a lower cost. In patients with gastrointestinal or genitourinary cancers however, a higher bleeding risk has been shown with DOACs. LMWHs thus remain the treatment of choice in this group of patients.. L’utilisation des anticoagulants oraux directs (ACOD) pour le traitement de la maladie thromboembolique veineuse (MTEV) chez les patients sans cancer est déjà largement implémentée. En cas de MTEV liée au cancer, les héparines de bas poids moléculaire (HBPM) et en particulier la daltéparine, ont longtemps ­représenté le traitement de référence. Suite à la publication de deux études randomisées récentes comparant l’édoxaban et le rivaroxaban à la daltéparine, les ACOD se sont révélés être une alternative efficace, avec un profil de sécurité satisfaisant, ­offrant par ailleurs le confort d’une administration orale et un coût moindre. Toutefois, en raison d’un risque hémorragique ­accru sous ACOD chez les patients avec un cancer de localisation digestive ou urogénitale, les HBPM restent le traitement de choix dans ce groupe de patients.

Topics: Administration, Oral; Anticoagulants; Dalteparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridines; Rivaroxaban; Thiazoles; Venous Thromboembolism

Non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit-risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug-drug interactions and preference for once- or twice-daily dosing. In addition, several 'special situations' were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Atrial Fibrillation; Benzamides; Biomarkers; Blood Coagulation; Clinical Trials as Topic; Dabigatran; Drug Administration Schedule; Factor Xa; Heart Diseases; Humans; Piperazines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Risk; Rivaroxaban; Stroke; Thiazoles; Thrombin; Venous Thromboembolism; Vitamin K; Warfarin

Until recently, heparins and vitamin K antagonists (VKAs) were the cornerstones for prevention and treatment of venous thromboembolism (VTE). This situation changed with the introduction of the direct oral anticoagulants, which are now replacing low-molecular-weight heparin for thromboprophylaxis after elective hip or knee arthroplasty and VKAs for VTE treatment. Rivaroxaban, an oral factor Xa inhibitor, was the first direct oral anticoagulant licensed for VTE prevention and treatment. This paper provides the rationale for factor Xa as a target for anticoagulants, describes the development of rivaroxaban, reviews its pharmacological profile, discusses the clinical trials with rivaroxaban for VTE prevention and treatment and highlights areas of uncertainty.

Topics: Administration, Oral; Blood Coagulation; Factor Xa Inhibitors; Humans; Rivaroxaban; Venous Thromboembolism

Many patients with venous thromboembolism (VTE) are at risk of recurrence if anticoagulant therapy is stopped. Whereas 3 months of anticoagulation treatment is sufficient for patients with VTE provoked by major surgery or trauma, in many cases a longer course is needed. Extended therapy with vitamin K antagonists (VKAs) requires frequent coagulation monitoring and dose adjustments to ensure that the international normalized ratio (INR) remains within the therapeutic range; furthermore, there is a risk of major bleeding even if a therapeutic INR is maintained. Therefore, more convenient and safer anticoagulants are needed.The non-VKA oral anticoagulants (NOACs)-apixaban, dabigatran, edoxaban and rivaroxaban-simplify extended therapy because they can be given in fixed doses without routine coagulation monitoring. Randomized clinical trials have demonstrated the efficacy and safety of NOACs for extended VTE treatment, but bleeding remains a concern. Patients and physicians may, therefore, be reluctant to continue anticoagulation beyond 3 to 6 months except in patients at high risk of recurrence. Acetylsalicylic acid (ASA) is often prescribed instead of an anticoagulant because of its perceived lower risk of bleeding; however, the recent EINSTEIN CHOICE trial demonstrated that once-daily rivaroxaban at a dose of either 20 or 10 mg reduced the risk of recurrent VTE by 70% compared with ASA without significantly increasing the risk of bleeding. In this review, we discuss the EINSTEIN CHOICE trial in the context of previous trials for extended VTE treatment and examine some of the lessons that can be applied to clinical practice.

Topics: Anticoagulants; Aspirin; Canada; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Hemorrhage; Humans; Recurrence; Risk; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Prophylactic anticoagulant therapy is recommended to reduce the risk of venous thromboembolism (VTE) after total hip or knee arthroplasty, and has become the standard of care. Rivaroxaban is a novel oral medication that directly inhibits factor Xa for the prevention and treatment of thromboembolic conditions.. A meta-analysis of randomized controlled trials (RCTs) was performed to determine the efficacy and safety of rivaroxaban after total hip arthroplasty (THA) and total knee arthroplasty (TKA) surgery. We reviewed several databases including PubMed, the Cochrane Library, Embase and the US trial registry to detect appropriate RCTs for our meta-analysis. The primary efficacy outcome of this meta-analysis was the combination of any deep-vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and death from any cause. The main safety outcome was bleeding events which included significant bleeding events, clinically relevant insignificant bleeding events, or minor events. Other end points were the number of patients who received blood transfusion the volume of transfused whole blood or red blood cells, and the volume of postoperative drainage.. Thirteen RCTs were included in this meta-analysis. This meta-analysis showed that the overall rate of VTE events, DVT, PE, and death were 1%, 6%, < 1% and < 1%, respectively, for patients receiving treatment with rivaroxaban after THA and TKA surgery. The subgroup analysis demonstrated rivaroxaban had more superior effects in THA patients. The pooled analysis of bleeding events showed that the overall rate of major bleeding events, overt bleeding events associated with fall in Hb of > 2 g/DL, clinically overt bleeding events leading to transfusion of > 2 units of blood, clinically overt bleeding events leading to further surgeries, and non-major bleeding events were < 1%, < 1%, < 1%, < 1%, and 3%, respectively.. This is the first systematic review of the literature providing incidence of efficacy and safety outcomes for thromboprophylaxis in THA and TKA patients. Moreover, this meta-analysis showed that rivaroxaban had more superior effect in THA patients.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer and anticoagulant treatment in these patients has remained a challenge. Cancer patients with VTE are at increased risk of developing recurrent VTE compared to patients without cancer, but also have a higher risk of major bleeding. In these patients, low molecular weight heparins (LMWHs) have been shown to be more effective and as safe as vitamin K-antagonists (VKAs) for the treatment of VTE. Therefore, the majority of current clinical guidelines recommend LMWHs as the treatment of choice for cancer-associated VTE. However, several issues should be considered regarding the use of LMWHs as daily subcutaneous injections, the costs or risk of heparin-induced thrombocytopenia. In recent years, direct-acting oral anticoagulants (DOACs) have shown similar efficacy and better safety profile compared to VKAs and have become the standard of care for the treatment of VTE in the general population. Because DOACs offer a simple oral treatment regimen without the need for anticoagulation control, they could be an attractive alternative to LMWH. Before DOACs become an accepted treatment option for cancer associated VTE, they have to be evaluated in a head-to-head comparison with LMWH. Data from two randomized trials comparing DOACs vs. LMWH have recently been published. In the present review, we will provide three clinically relevant questions on the use of DOACs in patients with cancer and VTE and provide an overview on recent evidence on this topic: 1) are DOACs a treatment option for the prevention of VTE in cancer patients?; 2) what is the place for DOACs in patients with cancer-associated VTE?; 3) should I use DOACs for the extended treatment of cancer-related VTE?.

Topics: Anticoagulants; Clinical Trials as Topic; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyridines; Rivaroxaban; Thiazoles; Venous Thromboembolism

Pulmonary embolism (PE) is the most feared clinical presentation of venous thromboembolism (VTE). Patients with PE have traditionally been treated in hospital; however, many are at low risk of adverse outcomes and current guidelines suggest outpatient treatment as an option. Outpatient treatment of PE offers several advantages, including reduced risk of hospital-acquired conditions and potential cost savings. Despite this, patients with low-risk PE are still frequently hospitalized for treatment. This narrative review summarizes current guideline recommendations for the identification of patients with low-risk PE who are potentially suitable for outpatient treatment, using prognostic assessment tools (e.g. the Pulmonary Embolism Severity Index [PESI] and simplified PESI) and clinical exclusion criteria (e.g. Hestia criteria) alone or in combination with additional cardiac assessments. Treatment options are discussed along with recommendations for the follow-up of patients managed in the non-hospital environment. The available data on outpatient treatment of PE are summarized, including details on patient selection, anticoagulant choice, and short-term outcomes in each study. Accumulating evidence suggests that outcomes in patients with low-risk PE treated as outpatients are at least as good as, if not better than, those of patients treated in the hospital. With mounting pressures on health care systems worldwide, increasing the proportion of patients with PE treated as outpatients has the potential to reduce health care burdens associated with VTE.

Topics: Administration, Oral; Anticoagulants; Cardiology; Drug Approval; Hemodynamics; Hospitalization; Humans; Length of Stay; Outpatients; Practice Guidelines as Topic; Prognosis; Pulmonary Embolism; Pyrazoles; Pyridones; Risk; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Cancer accounts for 20% of all venous thromboembolism (VTE) worldwide and cancer patients are at four- to sevenfold increased risk of thrombosis compared to non-cancer patients. VTE is also a morbid complication of cancer and its incidence is rising. Thrombosis is also a second leading cause of death in cancer patients. The standard of care management for the prevention and treatment of cancer-associated thrombosis (CAT) remains the administration of low-molecular-weight heparins (LMWHs). In the last decade, five direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban, have been approved for the treatment and prevention of VTE in the general patient population. In this review, we discuss the results of the already published clinical trials with DOACs in the treatment of CAT and the ongoing clinical trials with DOACs in the prevention and treatment of CAT.

Topics: Administration, Oral; Anticoagulants; Benzamides; Dabigatran; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism

: Rivaroxaban, a direct oral anticoagulant, is widely used for the treatment of venous thromboembolism (VTE) in adult patients. The approval of rivaroxaban for the treatment of deep vein thrombosis and pulmonary embolism and the extended secondary prevention of recurrent VTE is based on the results of the EINSTEIN DVT and EINSTEIN PE trials, and the EINSTEIN EXT and EINSTEIN CHOICE trials, respectively. This review provides an updated overview of these completed EINSTEIN studies in adult patients, including results of subanalyses in patients at high risk of recurrent VTE, and discusses the emerging data from the EINSTEIN Junior programme, which is evaluating the use of rivaroxaban for the treatment of paediatric VTE. In the EINSTEIN DVT and EINSTEIN PE trials, rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily thereafter) was shown to be an effective and safe alternative to standard anticoagulation for the treatment of deep vein thrombosis and pulmonary embolism in a broad range of adult patients. These results are supported by increasing amounts of real-world data from patients treated with rivaroxaban in routine clinical practice worldwide. In the EINSTEIN EXT and EINSTEIN CHOICE trials, rivaroxaban was superior to placebo and acetylsalicylic acid, respectively, for the extended treatment of VTE - physicians can now choose between two doses of rivaroxaban (20 mg once daily or 10 mg once daily) for the extended prevention of recurrent VTE, based on a patient's risk of recurrence, bleeding and personal preferences.

Topics: Adult; Aspirin; Child; Clinical Trials as Topic; Humans; Precision Medicine; Pulmonary Embolism; Rivaroxaban; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis

Cancer patients with cancer-associated thrombosis (CAT) are at an elevated risk of recurrent venous thromboembolism (VTE) and of major bleeding while receiving treatment with anticoagulation. Recently, Xa inhibitors have been assessed in cancer patients for the treatment of CAT, providing clinicians and patients with more treatment options.. In this narrative review, the authors evaluate the evidence regarding the efficacy and safety of edoxaban, rivaroxaban, and apixaban in the treatment of CAT.. Xa inhibitors are an effective, safe, and convenient option for the treatment of CAT. Overall, they may be associated with a lower risk of recurrent VTE in cancer patients. Certain subgroups of cancer patients may be at increased risk of major bleeding while on treatment with Xa inhibitors, when compared to low-molecular-weight-heparin (LMWH). The current published data suggests an increase in gastrointestinal (GI) major bleeding in patients with GI malignancies. Other patient, treatment, and cancer characteristics may also be associated with a higher risk of major bleeding. Therefore, when assessing the appropriateness of Xa inhibitors for the treatment of CAT, the clinician must take into consideration the known interactions of these drugs, the individualized bleeding risk, and the patient's preferences, in order to make the best possible anticoagulation therapy recommendation.

Topics: Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

Total knee arthroplasty is an elective procedure performed on relatively healthy individuals. However, due to the inherent risk of venous thromboembolism, drugs are used for its prophylaxis. The objective of the present study was to conduct a systematic review of the literature to compare the efficacy of enoxaparin and rivaroxaban in preventing this complication and the risk of intraoperative bleeding. We reviewed the SciELO, Pubmed and Cochrane databases with the descriptors knee arthroplasty, rivaroxaban and enoxaparin through the PICO search strategy. Inclusion criteria were the articles during the study period comparing both drugs in knee arthroplasty. Relevant criteria to study eligibility were articles published since 2010 and with a sample of more than 20 patients; studies obtained in their entirety; and studies with follow-up of more than 12 months. The variables used to compare the articles were the most common postoperative complications of knee arthroplasties: venous thromboembolism and bleeding. We used the Review Man software, version 5.3, for structuring the review. In the studies analyzed, considering symptomatic venous thromboembolism, rivaroxaban resulted in higher benefits when compared to enoxaparin.. A artroplastia total do joelho é um procedimento eletivo, realizado em indivíduos relativamente saudáveis. Porém, devido ao risco inerente de tromboembolismo venoso, são utilizados fármacos para sua profilaxia. O objetivo do presente trabalho foi conduzir uma revisão sistemática da literatura para comparar a eficácia da enoxaparina e da rivaroxabana na prevenção desta complicação e no risco de sangramento intraoperatório. Foi feita uma revisão no site SciELO, Pubmed e Cochrane através dos descritores, artroplastia de joelho, rivaroxabana e enoxaparina através da estratégia de busca PICO. Os critérios de inclusão foram os artigos no período estudado, que comparavam ambas as drogas em cirurgias de artroplastia do joelho. Os critérios de relevância para tornar o estudo elegível foram definidos como: somente artigos publicados a partir 2010 e com casuística com mais de 20 pacientes foram considerados; somente estudos obtidos em sua íntegra foram analisados; somente estudos com seguimento maior do que 12 meses foram considerados relevantes. As variáveis utilizadas para a comparação dos artigos foram as complicações mais comuns no pós-operatório de artroplastias do joelho: tromboembolismo venoso e sangramento. Foi utilizado o Review Man 5.3 para estruturação da revisão. Os autores observaram que nos estudos analisados, considerando tromboembolismo venoso sintomático, a rivaroxabana resultou em maiores benefícios quando comparada com a enoxaparina.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Enoxaparin; Humans; Postoperative Complications; Postoperative Hemorrhage; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

The review is devoted to the issue of optimal duration of anticoagulant therapy for venous thromboembolic complications (VTEC) using oral anticoagulants (OAC). These drugs are characterized by higher safety in comparison with vitamin K antagonists and make it possible to increase the duration of treatment for not only spontaneous thrombosis (with high risk of recurrence), but also thrombosis provoked by minor persistent and transient risk factors of VTEC. Efficacy and safety of prolonged treatment of VTEC using OAC was analyzed. Different classifications of primary thrombotic episode depending on risk of subsequent recurrence are presented. Moreover, scales for individual assessment of risk of recurrent thrombosis after anticoagulant therapy cancellation and risk of bleeding in case of continued treatment are given. Outcomes of long-term administration of rivaroxaban for VTEC are analyzed. It was concluded that OAC are safe for prolonged management of primary thrombotic episode. However, overall duration of treatment should be determined considering individual balance of benefits and risks.. Статья представляет собой классический обзор литературы, посвященный вопросам определения оптимальной длительности антикоагулянтной терапии венозных тромбоэмболических осложнений (ВТЭО) в свете широкого внедрения прямых оральных антикоагулянтов (ПОАК). Последние, обладая в сравнении с антагонистами витамина K улучшенным профилем безопасности, позволяют увеличивать длительность лечения не только клинически неспровоцированных тромбозов (наиболее опасных в отношении рецидива), но и спровоцированных малыми персистирующими и транзиторными факторами риска ВТЭО, характеризующихся меньшей угрозой. Проведен анализ результатов исследований по изучению эффективности и безопасности продленной терапии ВТЭО с помощью ПОАК. Представлены различные классификации первичного тромботического эпизода в зависимости от его влияния на риск рецидива, приведены шкалы для индивидуальной оценки угрозы повторного тромбоза после отмены антикоагулянта и опасности кровотечения при продолжении лечения. Проанализированы результаты длительного применения ривароксабана при спровоцированных ВТЭО. Сделан вывод, что применение ПОАК позволяет безопасно увеличивать продолжительность терапии первичного эпизода, однако общая длительность лечения должна быть основана на индивидуальном балансе пользы и риска.

Topics: Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Humans; Recurrence; Risk Factors; Rivaroxaban; Thrombosis; Time Factors; Venous Thromboembolism; Withholding Treatment

Currently there is significant variation in the management of venous thromboembolism prophylaxis following total knee arthroplasty (TKA). Excessive wound ooze and bleeding is thought to increase a patient's risk of haematoma formation and possible infection. We evaluated the rate of unexpected reoperation in the perioperative period in patients who received aspirin, rivaroxaban or enoxaparin following primary TKA.. A systematic literature search was conducted in MEDLINE, CENTRAL and Embase to identify patients who underwent primary TKA. Two researchers independently reviewed the references identified in the literature search. The final 11 studies included for review were published between 1996 and 2016.. There was a higher rate of reoperation in patients treated with aspirin following TKA when compared to enoxaparin and rivaroxaban in the perioperative period. Of the 5141 patients treated with enoxaparin, 11 (0.21%) required reoperation; of the 2764 patients treated with rivaroxaban, 12 (0.43%) required reoperation; and of the 228 patients treated with aspirin, seven (3.07%) required reoperation. The average time to follow-up in the 11 studies was 55 days, ranging from 30 to 180 days post-operatively.. There was a higher rate of reoperation in patients treated with aspirin following TKA when compared to enoxaparin and rivaroxaban in the perioperative period. While there is extensive data on the safety and efficacy of these medications following joint arthroplasty, improved reporting of surgically relevant outcomes are needed to assist both the surgeon and patient in clinical decision-making.

Topics: Arthroplasty, Replacement, Knee; Aspirin; Australia; Case-Control Studies; Clinical Decision-Making; Enoxaparin; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Perioperative Period; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Reoperation; Rivaroxaban; Safety; Treatment Outcome; Venous Thromboembolism

Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Direct oral anticoagulants (DOACs) have become widely used to treat patients with venous thromboembolism (VTE), but evidence about their use in the treatment of upper extremity deep vein thrombosis (UEDVT) is lacking.. To assess rivaroxaban's efficacy and safety in the treatment of UEDVT.. This was a single-center prospective observational study involving patients with their first UEDVT episode confirmed by duplex ultrasound scan. All patients initially received low-molecular-weight heparin for 1 to 2 days and then were switched to rivaroxaban for 3-6 months. The primary endpoint was any symptomatic episode of recurrent VTE.. Thirty patients were included in the study, and all patients were followed for 6 months. There were no episodes of recurrent symptomatic venous thromboembolism or asymptomatic UEDVT. No episode of major bleeding was observed. Clinically relevant non-major bleeding occurred in two patients (6.7%, 95% confidence interval [CI]: 1.9-21.4%) with uterine bleeding and large skin hemorrhage. Minor bleeding was observed in two patients (6.7%, 95% CI: 1.9-21.4%) presenting with nasal and gingival bleeding. Recanalization of the upper extremity deep veins was observed in all affected limbs at three months, and it persisted up to 6 months. The signs of upper limb post-thrombotic syndrome (PTS) were found in four patients (13.4%; 95% CI: 5.4-29.8%), and the mean modified Villalta score was 2.1 ± 1.9.. Treatment of UEDVT with rivaroxaban, preceded by one to two days of LMWH, seems to be safe and effective.

Topics: Adult; Aged; Anticoagulants; Female; Humans; Male; Middle Aged; Prospective Studies; Rivaroxaban; Upper Extremity Deep Vein Thrombosis; Venous Thromboembolism

Topics: Administration, Oral; Evidence-Based Medicine; Factor Xa Inhibitors; Humans; Neoplasms; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

 This article evaluates the preventive effects of rivaroxaban versus aspirin on venous thromboembolism (VTE) through meta-analysis of recent randomized controlled trials (RCTs)..  RCTs were retrieved from medical literature databases. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare the primary and safety endpoints..  In total, 9 trials (11 trial comparisons) were retrieved which contained 7,656 patients. Among these patients, 4,383 patients (57.2%) received rivaroxaban, whereas 3,273 patients (42.8%) received aspirin. Compared with aspirin, rivaroxaban significantly reduced VTE (1.3% vs. 3.5%) (RR: 0.36, 95% CI, 0.26-0.48,.  This meta-analysis indicated that rivaroxaban can significantly reduce the incidence of VTE when compared with aspirin. The preventive effect of rivaroxaban on VTE was more potent than that of aspirin. However, rivaroxaban had some negative side effects to patients such as nonmajor bleeding compared to aspirin.

Topics: Administration, Oral; Anticoagulants; Aspirin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

Venous thromboembolism (VTE) is a significant healthcare burden with approximately 900,000 events annually in the United States, over half of which are healthcare-associated. This number is anticipated to double by 2050. Group prophylaxis strategies confined to the inpatient setting appear to have minimal impact on the reduction of post-discharge VTE in medically ill patients due to shortened lengths of stay and a heterogenous population that includes patients at low risk for VTE. In accordance with current guideline recommendations, very few (<5%) medically ill patients are discharged with extended prophylaxis, which potentially creates a clinical gap for at-risk patients as VTE risk has been shown to persist for up to 90 days. Initial studies of extended thromboprophylaxis in acutely ill medical patients with enoxaparin, rivaroxaban and apixaban showed little to no benefit towards VTE reduction that was consistently outweighed by increased bleeding. The more recent APEX study that compared betrixaban to enoxaparin in an enriched patient population at high-risk for VTE was the first study of extended thromboprophylaxis that showed similar efficacy in VTE prevention without an increase in major bleeding. Based on the APEX results, betrixaban recently gained FDA approval for extended thromboprophylaxis in acutely ill medical patients. Recognition that up to half of medically ill patients are not at sufficient risk to warrant thromboprophylaxis has driven extensive research towards development of scientifically derived and validated VTE risk assessment models intended to identify patients who do not warrant prophylaxis, as well as those at high risk who may derive benefit from extended thromboprophylaxis. This article will review prior and ongoing extended thromboprophylaxis studies, VTE and bleed risk assessment models, incorporation of biomarkers in VTE risk assessment and key issues in the paradigm shift towards individualized VTE prophylaxis in acutely ill medical patients.

Topics: Age Factors; Anticoagulants; Benzamides; Drug Administration Schedule; Enoxaparin; Hemorrhage; Hospitalization; Humans; Meta-Analysis as Topic; Mobility Limitation; Patient Discharge; Pyridines; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Venous Thromboembolism

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Stroke; Thiazoles; Venous Thromboembolism; Withholding Treatment

Patients with end-stage renal disease (ESRD) were excluded from pivotal clinical trials with oral anticoagulants. While such patients are at an increased risk of venous and arterial thromboembolism, their risk of bleeding is also elevated. It is thus of little surprise that stroke prevention with vitamin K antagonists (VKAs) in ESRD patients with atrial fibrillation is controversial, with observational evidence ranging from beneficial to harmful. This uncertainty extends to the less studied use of VKAs for venous thromboembolism in ESRD. The direct oral anticoagulants (DOACs) apixaban and rivaroxaban have now permissive labeling in the United States for atrial fibrillation in patients with ESRD; this expanded labeling has not yet occurred either in Europe or for venous thromboembolism. This review summarizes the current evidence for the pharmacology of DOACs in ESRD as well as their utilization and safety in patients with ESRD and atrial fibrillation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Rivaroxaban; United States; Venous Thromboembolism; Vitamin K

The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007.. To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications.. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings.. Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein.. Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach.. We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects.. Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Rivaroxaban; Stockings, Compression; Thrombectomy; Thromboembolism; Thrombophlebitis; Venous Thromboembolism

Acute pulmonary embolism (PE) is a relatively common cardiopulmonary emergency that is a major cause of hospitalization and morbidity and is the primary cause of mortality associated with venous thromboembolism (VTE). During the last decade, one of the biggest changes in the management of PE has been the approval of four non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) for the treatment of PE and deep vein thrombosis and secondary prevention of VTE. Areas covered: This article reviews the evolving management of PE in the NOAC era and addresses three fundamental questions: who should receive NOACs over conventional heparin/vitamin K antagonist regimens for the treatment of acute PE; should patients be treated as inpatients or outpatients; and how long should patients be treated to reduce the risk of recurrence? Expert commentary: The management of PE is changing. NOACs provide new anticoagulant treatment options for patients with PE, based on Phase III clinical study results. The consistent efficacy and safety profile of NOACs across many PE patient subgroups, including the elderly, fragile patients, those with active cancer and high-risk (right ventricular dysfunction) patients, suggests NOAC use will increase among these patients.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism

Venous thromboembolism (VTE) presents a continuing clinical burden to healthcare systems and there are patient groups for whom VTE management is challenging. Depending on the patient profile, the optimal duration of anticoagulation for VTE treatment can be unclear. EINSTEIN CHOICE was a Phase III, randomized, double-blind trial that compared the safety and efficacy of two once-daily (od) doses of the direct, oral factor Xa inhibitor rivaroxaban (20 and 10 mg) with acetylsalicylic acid (ASA; 100 mg daily) for prevention of recurrent VTE. Extended therapy with rivaroxaban at either dose was more effective than ASA at preventing recurrent VTE without increasing bleeding risk. Another group that is challenging to treat in the context of VTE is patients with cancer-associated thrombosis. Cancer is associated with a hypercoagulable state, while cancer treatment itself may increase VTE risk. Evidence supporting the use of non-vitamin K antagonist oral anticoagulants in patients with cancer is growing through specifically designed studies. Cancer Associated thrombosis-expLoring soLutions for patIentS through Treatment and prevention with rivarOxaban (CALLISTO) is an international research program exploring the role of rivaroxaban for the prevention and treatment of cancer-associated thrombosis. Here, we present overviews of three CALLISTO studies: PRO-LAPS II, CASTA-DIVA and COSIMO. Currently available and anticipated results from studies in a variety of patients at risk of or with VTE will provide valuable insights and seek to optimize future VTE management.

Topics: Blood Coagulation; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Patients with chronic kidney disease (CKD) are at increased risk of atrial fibrillation, stroke, and bleeding posing unique clinical challenges. Novel oral anticoagulants (NOACs) including dabigatran, rivaroxaban, and apixaban have become recognized as alternative therapy to Vitamin K Antagonists (VKA) regarding the prevention of venous thromboembolism (VTE) and reduce the risk of stroke in atrial fibrillation. However, the understanding of NOACs in CKD is still underdeveloped. This review summarizes recent literature on the efficacy and safety of NOACs in patients with CKD.. Studies focusing on patients with moderate kidney disease were drawn from post hoc analyses from three major NOAC trials, meta-analyses, and postmarketing surveillance studies. Cumulatively, these studies continue to demonstrate NOACs as equivalent if not superior therapies to VKAs in regards to both efficacy and safety. These studies are limited by small sample sizes as well as a lack of direct comparison between NOACs.. The role of NOACs in managing VTE and atrial fibrillation is increasing. Current research suggests that NOACs are at least as efficacious and well tolerated as VKAs. More research is required to elucidate which NOAC is preferable in the clinical setting.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Risk Factors; Rivaroxaban; Stroke; Venous Thromboembolism

While not designated as guideline-recommended first-line anticoagulation therapy, about one in five patients in the United States receive rivaroxaban for the treatment of cancer-associated venous thrombosis (CAT).. A systematic review and meta-analysis were performed to evaluate the incidences of recurrent venous thromboembolism (VTE), major bleeding, and all-cause mortality in rivaroxaban patients treated for CAT in routine practice. Literature searches of MEDLINE and SCOPUS were performed through September 2017 to identify real-world studies of ≥ 20 patients evaluating the incidence of recurrent VTE, major bleeding, or all-cause mortality in CAT patients anticoagulated with rivaroxaban. Using a Hartung-Knapp random-effects model, the pooled incidence estimates and 95% confidence intervals (CIs) were calculated for each end point.. Six studies evaluating rivaroxaban for CAT were identified. Of these, three were prospective and three were retrospective. Study sample sizes ranged from 41 to 949 patients, and duration of follow-up ranged from 164 to 496 days. The most frequent active cancer sites reported in studies were gastrointestinal (range: 12.0-56.0%), genitourinary (range: 8.6-26.0%), and breast (range: 9.3-25.5%). The weighted average incidences of recurrent VTE, major bleeding, and all-cause mortality were 4.2% (95% CI = 2.6-6.6%; I. This meta-analysis suggests that incidences of recurrent VTE and major bleeding among rivaroxaban-managed patients are not dissimilar to those seen in recent randomized trials of anticoagulation in CAT. The pooled incidence for mortality was lower than reported in many anticoagulation CAT trials. This may suggest that rivaroxaban is being used in CAT patients who have less severe cancer.

Topics: Factor Xa Inhibitors; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

The incidence of venous thromboembolism (VTE) in adult patients with sickle cell disease (SCD) is high. However, overlapping features between the clinical presentation of VTE and SCD complications and a low index of suspicion for thrombosis can influence patient management decisions. VTE in SCD can therefore present management challenges to the clinical hematologist. Herein, we present 3 distinct clinical vignettes that are representative of our clinical practice with SCD patients. These vignettes are discussed with specific reference to the hypercoagulable state in SCD patients, recent VTE diagnosis and anticoagulant therapy guidelines from the general population, and evaluation of the risk of bleeding as a result of long-term exposure to anticoagulant therapy. We examine current diagnostic and treatment options, highlight limitations of the existing clinical prognostic models that offer personalized guidance regarding the duration of anticoagulation, and propose a clinical approach to guide the decision to extend anticoagulation beyond 3 months.

Topics: Adult; Anemia, Sickle Cell; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Male; Pregnancy; Pregnancy Complications; Rivaroxaban; Venous Thromboembolism

Until recently, vitamin K antagonists (VKA) were the only drugs available for long-term anticoagulation. The use of these drugs is laborious due to their variable pharmacokinetics and pharmacodynamics. The advent of direct oral anticoagulants has produced a paradigm shift due to their low incidence of drug interactions, their stable plasma levels, and their lack of monitoring. Rivaroxaban, a factor Xa inhibitor, has been tested in different clinical scenarios and has proved to be effective and safe, even increasing the scope of the old VKA. Areas covered: A non-systematic review of the literature was conducted using the PubMed and Cochrane databases, focusing on randomized clinical trials and real-world observational studies that evaluated rivaroxaban in patients with atrial fibrillation, venous thromboembolism, and atherosclerotic coronary and peripheral vascular disease. Expert commentary: The role of rivaroxaban keeps expanding into areas that were unimaginable few years ago, in the light of solid evidence that has eliminated old strict paradigms. Nonetheless, it will be necessary to adjust costs and better understand the perceived barriers to its widespread implementation, to get fully acceptation of rivaroxaban for the different clinical conditions that have been suggested.

Topics: Administration, Oral; Atrial Fibrillation; Blood Coagulation; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Venous Thromboembolism

Atrial fibrillation, peripheral and coronary artery disease, and venous thromboembolism are major risk factors for stroke, disability, and death in the rapidly growing older (≥ 65 years.) population. In the absence of clear guidelines on the appropriate use of the newer non-vitamin K antagonist oral anticoagulants in this population, this study specifically reviews the available literature for rivaroxaban and the impact of age that may affect the pharmacokinetics, pharmacodynamics, efficacy, and safety of this anticoagulant.. This review includes a summary of data obtained from the available literature concerning both older healthy subjects and older patients with various aspects of cardiovascular disease enrolled in rivaroxaban clinical trials and data from real world evidence studies.. Evaluation of the clinical pharmacology in healthy, older adults reveal no clinically relevant effect of age on rivaroxaban pharmacokinetics and pharmacodynamics. Population pharmacokinetic studies in older patients with thromboembolic diseases suggest a moderate effect of increasing age on rivaroxaban clearance, albeit not clinically significant. Additionally, sub-group analyses from large, phase 3 clinical trials demonstrate consistent efficacy and safety in the older patient population vs the overall population. These findings are further supported by real-world evidence studies.. A favorable clinical profile with rivaroxaban was observed across age sub-groups, supporting the premise that dosing in older adults does not necessitate adjustment. However, it is prudent that a cautious and individualized approach is taken for treatment with any anticoagulant in older adults.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Humans; Risk Factors; Rivaroxaban; Stroke; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are increasingly used for anticoagulation or prevention of thromboembolic events in conditions that may co-occur with pregnancy. However, evidence regarding efficacy and safety during pregnancy is scarce.. To review the current literature concerning the efficacy, safety and outcome of DOACs during pregnancy in humans.. We systematically searched the MedLine public database for all studies describing the use of DOACs during pregnancy published up to July 4th 2017.. 236 cases of DOAC use during pregnancy were reported. Rivaroxaban was the most reported DOAC (n = 178). DOACs were mostly used for prophylaxis or treatment of venous thromboembolism (n = 91). DOACs were discontinued within the first 2 months of pregnancy in 84%, maximum reported duration of use was 26 weeks. Pregnancy outcome data were available for 140 pregnancies. Thirty-nine pregnancies were electively terminated. In the remaining 101 pregnancies total miscarriage rate was 31% (n = 31) and live birth rate was 68% (n = 69, 1 missing). Foetal and neonatal abnormalities were reported in 8 pregnancies, of which at least half were suspected to be related to rivaroxaban use during the 1st trimester of pregnancy. In only 18% of cases (n = 42), the presence or absence of thrombotic and bleeding complications was reported.. The limited available evidence raises concern regarding embryo-foetal safety, with high incidence of miscarriages and a 4% rate of anomalies with the use of rivaroxaban. Not enough data are available to judge safety and efficacy of the use of DOACs during pregnancy.

Topics: Administration, Oral; Anticoagulants; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Rivaroxaban; Venous Thromboembolism

Although low-molecular-weight heparin (LMWH) is recommended as the first-line treatment in patients with active cancer and venous thromboembolism (VTE), many patients are more willing to choose oral anticoagulants. We collected currently available data to evaluate the efficacy and safety of the oral direct factor Xa inhibitor rivaroxaban compared with enoxaparin in patients with cancer and VTE.. We retrieved electric databases, including Medline/PubMed and EMBASE, from inception through January, 2018. We included articles comparing enoxaparin with rivaroxaban in patients with cancer and VTE. Recurrences of VTE, incidence of major bleeding and deaths were compared between groups. Poole analysis was conducted in Review Manager Version 5.2.. A total of 4 articles and 667 patients were included in the final analysis. Pooled analysis showed that rivaroxaban was associated with a non-significantly lower recurrence of VTE (risk ratio [RR] = 0.55, 95% confidence interval (95%CI): 0.28-1.06, I = 0%). Patients treated with rivaroxaban had a similar major bleeding risk compared with those administrated with enoxaparin (RR = 0.84, 95%CI: 0.39-1.83, I = 0%). No significant difference was observed in mortality between the 2 groups (RR = 0.51, 95%CI: 0.15-1.80, I = 89%).. Rivaroxaban is as effective and safe as enoxaparin for the prevention of recurrent VTE in patients with malignancy. Rivaroxaban is a potential option for patients with cancer and VTE.

Topics: Anticoagulants; Enoxaparin; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

Solid organ transplant patients are at risk of developing atrial fibrillation and venous thromboembolism. Direct oral anticoagulants are considered an attractive option for anticoagulation in patients due to their convenience; however, strong evidence of their use in transplantation is lacking. We conducted a search using Pubmed, Embase, and Scopus databases, in addition to International Society of Heart and Lung transplantation and American Transplant Congress abstracts (from 2012 through December 2017). Fourteen articles were reviewed that included case reports, retrospective case series, or chart review analyses of small cohorts. Based on this review, the findings can only generate hypotheses that should be further studied in a larger randomized cohort. This review can help clinicians gain insight into the use of direct oral anticoagulant in this special population. For now, clinicians should be cautious about their use in this special population.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Humans; Male; Middle Aged; Organ Transplantation; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

To compare the efficacy and safety of rivaroxaban, apixaban and enoxaparin for thromboprophylaxis after arthroplastic surgery.. We conducted a meta-analysis containing a wide range of randomized controlled trials about efficiency and safety of rivaroxaban, apixaban and enoxaparin for thromboprophylaxis after arthroplastic surgery in the recent decade from January 2006 to June 2018. The present study separately analyzed the following key components: the different efficiency and safety for rivaroxaban and enoxaparin; apixaban and enoxaparin; and enoxaparin and other new developed anticoagulants.. Sixteen studies containing 58885 patients were included. In results of efficacy outcomes, total events occurred in 4.89% patients of rivaroxaban group and 9.55% patients of the control group; however, no significant difference was observed in apixaban groups of their efficacy outcomes. Primary events didn't show significant difference when comparing apixaban with the control or comparing enoxaparin with the control. In analysis of safety outcomes, bleeding events occurred in 3.41% patients of rivaroxaban group compared with 2.84% patients of the control groups; bleeding events in apixaban groups were 4.09% compared with the control groups 4.64%. Bleeding events occurred in 3.51% patients of enoxaparin group, slightly lower than 5.82% of the control group.. Direct oral anticoagulant, rivaroxaban might have better efficacy outcomes in thromboprophylaxis after arthroplastic surgery; however, apixaban showed no significantly different efficacy outcomes compared with enoxaparin, and enoxaparin may have equal or even better safety outcomes compared with direct oral anticoagulants.

Topics: Anticoagulants; Arthroplasty; Enoxaparin; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

This article analyzed the clinical efficacy and tolerability of rivaroxaban and enoxaparin in patients undergoing total knee arthroplasty (TKA) surgery.. Five randomized, controlled clinical trials on rivaroxaban versus enoxaparin in patients who underwent TKA were identified and included in this meta-analysis.. The meta-analysis indicated that rivaroxaban prophylaxis was associated with lower rates of symptomatic venous thromboembolism (VTE) (relative risk[RR]:0.55; 95% confidence interval [CI]: 0.35-0.86; P = .009), symptomatic deep vein thrombosis (DVT) (RR 0.44, 95% CI 0.25-0.80, P = .007), asymptomatic DVT (RR: 0.57; 95% CI: 0.37-0.89; P = .01), distal DVT (RR: 0.62; 95% CI: 0.45-0.85; P = .003) and proximal DVT (RR: 0.42; 95% CI: 0.24-0.75; P = .004). Compared with the enoxaparin group, the incidence of symptomatic pulmonary embolism (PE) (RR: 0.48; 95% CI: 0.19-1.24; P = .13) in the rivaroxaban group was not significantly different. A nonsignificant trend towards all-cause death (RR: 0.38; 95% CI: 0.03-4.92; P = .46) or major bleeding (RR: 1.59; 95% CI: 0.77-3.27; P = .21) risk between rivaroxaban and enoxaparin prophylaxis was found.. Compared with the enoxaparin group, the group using rivaroxaban after TKA had a significantly lower rate of symptomatic VTE, symptomatic DVT, asymptomatic DVT, distal DVT, and proximal DVT. Our study shows that rivaroxaban after TKA is more effective than enoxaparin and did not increase major bleeding or all-cause mortality.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Humans; Male; Middle Aged; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Rivaroxaban, dabigatran, apixaban and edoxaban are the four available new oral anticoagulants (NOAC) which are currently approved for venous thromboembolism prophylaxis after total hip and knee replacement. Large phase 3 and phase 4 studies comparing NOAC with low molecular weight heparins have shown similar results regarding the efficacy and safety of these two categories of anticoagulants. Management of bleeding complications is a matter of great significance. Three reversal agents have been developed: idarucizumab, andexanet alfa and ciraparantag. Idarucizumab is now commercially available. Regarding the perioperative management of NOAC, two main scientific groups have published their own recommendations. The European Heart Rhythm Association recommends 48-h period of stoppage preoperatively for factor Xa inhibitors and at least 3 or 4 days for dabigatran, while the French Study Group on Thrombosis and Haemostasis recommends 5-day discontinuation for all NOAC. Conventional clot tests can only be used as rough indicators for laboratory assessment of the activity of NOAC. Specific laboratory tests have been developed for more accurate measurements of NOAC blood levels, including a dilute thrombin time test (Hemoclot test) and the ecarin clot test for dabigatran and chromogenic anti-factor Xa assays for direct factor Xa inhibitors. Due to the beneficial properties of NOAC, these drugs are gaining ground in daily orthopaedic practice, and many studies are being conducted in order to extend the indications of these anticoagulants agents.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Blood Coagulation Tests; Dabigatran; Factor Xa; Hemorrhage; Humans; Orthopedic Procedures; Piperazines; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiazoles; Venous Thromboembolism

Direct oral anticoagulants (DOACs) were developed to compensate for the demerits of warfarin. In Japan, three factor Xa inhibitors are used for the treatment of venous thromboembolism (VTE): edoxaban, rivaroxaban, and apixaban. Despite problems, such as the inability to monitor their effect and the lack of an antidote, these inhibitors have the same efficacy as conventional treatment with warfarin, and they are associated with a significantly high degree of safety in relation to hemorrhagic complications. East Asians, including Japanese, suffer from hemorrhage more frequently; therefore, DOACs are considered to be highly effective. Although there is no evidence to date, DOACs may be effective in a wide variety of ways, including the possibility that they prevent recurrence over the long term, reduce the length of hospitalization, allow treatment to be started on an outpatient basis, and be effective in cancer patients.

Topics: Administration, Oral; Anticoagulants; Clinical Trials as Topic; Factor Xa Inhibitors; Hemorrhage; Hospitalization; Humans; Japan; Neoplasms; Outpatients; Platelet Count; Pyrazoles; Pyridines; Pyridones; Recurrence; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

Cancer patients with venous thromboembolism (VTE) are at increased risk for both bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin (LMWH) is the standard of care during the initial and long-term treatment phase (i.e. during the first 3 - 6 months of therapy) based on its overall beneficial safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are approved for the treatment of acute VTE, and the combined six phase-3 trials have included > 1500 patients with active cancer, as defined by variable selection criteria. Subgroup analyses of these patients, either pooled or separately reported, suggest that DOACs could be a safe and efficacious alternative to VKA therapy for the treatment of cancer-associated VTE. However, the populations of cancer patients included in the DOAC and LMWH trials are not comparable with regard to mortality and VTE risk, and no specific data from direct head-to-head comparisons of DOACs with LMWHs are currently available. The use of DOACs for the management of VTE in cancer is thus not recommended by clinical practice guidelines.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism

Venous thromboembolism causes significant morbidity and mortality in patients after total joint arthroplasty. Although network meta-analyses have demonstrated a benefit of various thromboprophylactic agents, there remains a concern in the surgical community regarding the resulting wound complications. There is currently no systematic review of the surgical site bleeding complications of thromboprophylactic agents. The aim of this study was to systematically review the surgical site bleeding outcomes of venous thromboembolism prophylaxis in this population.. A systematic review and meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials comparing more than one of low-molecular-weight heparin (LMWH), warfarin, rivaroxaban, apixaban, dabigatran, aspirin, or no pharmacologic treatment in patients after total hip or knee arthroplasty were selected for inclusion. Five meta-analyses were performed to compare LMWH with control, warfarin, apixaban, rivaroxaban, and dabigatran.. Forty-five randomized controlled trials of 56,730 patients were included. LMWH had a significantly increased relative risk of surgical site bleeding in comparison with control (relative risk, 2.32; 95% confidence interval, 1.40-3.85) and warfarin (1.54; 1.23-1.94). The relative risk of LMWH trended higher than apixaban (1.27; 1.00-1.63) and was similar to rivaroxaban (0.95; 0.74-1.23). Only 1 study reported the risk of surgical site bleeding in LMWH vs dabigatran (5.97; 2.08-17.11).. LMWH increased the risk of surgical site bleeding compared with control, warfarin. and dabigatran and trended toward an increased risk compared with apixaban. The risk of surgical site bleeding was similar with LMWH and rivaroxaban.

Topics: Anticoagulants; Arthroplasty; Arthroplasty, Replacement, Knee; Aspirin; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

It is unclear if the risk of intraocular bleeding with novel oral anticoagulants differs compared with warfarin.. To characterize the risk of intraocular bleeding with novel oral anticoagulants compared with warfarin.. A systematic review and meta-analysis was undertaken in an academic medical setting. MEDLINE and ClinicalTrials.gov were searched for randomized clinical trials published up until August 2016. This search was supplemented by manual bibliography searches of identified trials and other review articles.. Studies were eligible for inclusion if they were phase 3 randomized clinical trials, enrolled patients with atrial fibrillation or venous thromboembolism, compared a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) with warfarin, and recorded event data on intraocular bleeding. Data on intraocular bleeding were pooled using inverse-variance, weighted, fixed-effects meta-analysis.. The PRISMA guidelines were used for abstracting data and assessing quality. Independent extraction was performed by 2 investigators.. Intraocular bleeding events and associated risk ratio for novel oral anticoagulants compared with warfarin.. Twelve trials investigating 102 627 patients were included. Randomization to novel oral anticoagulants was associated with a 22% relative reduction in intraocular bleeding compared with warfarin (risk ratio, 0.78; 95% CI, 0.61-0.99). There was no significant heterogeneity observed (I2 = 4.8%, P = .40). Comparably lower risks of intraocular bleeding with novel oral anticoagulants were seen in subgroup analyses, with no significant difference according to the indication for anticoagulation (P for heterogeneity = .49) or the novel oral anticoagulant type (P for heterogeneity = .15). Summary estimates did not differ materially when random-effects meta-analytic techniques were used.. These results suggest that novel oral anticoagulants reduce the risk of intraocular bleeding by approximately one-fifth compared with warfarin. Similar benefits were seen in both patients with atrial fibrillation and venous thromboembolism. Our data have particular relevance for patients at higher risk of spontaneous retinal and subretinal bleeding. These findings may also have important implications in the perioperative period, in which the use of novel oral anticoagulants may be superior. Future studies are required to better characterize the optimal management of patients with both ophthalmic disease and cardiovascular comorbidities requiring anticoagulation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Eye Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

We respond to comments by Dufrost et al. about the RAPS trial, in particular, showing that the trial did achieve its target sample size; pointing out that thrombin potential is not synonymous with overall thrombin generation; confirming that overall, no increased thrombotic risk was evident comparing rivaroxaban with warfarin; and that high-risk patients (28% were triple positive, representative of patients with venous thromboembolism requiring standard-intensity anticoagulation) were included; and clarifying our rationale for using a laboratory surrogate primary outcome measure instead of a clinical one.

Topics: Anticoagulants; Antiphospholipid Syndrome; Humans; Rivaroxaban; Venous Thromboembolism; Warfarin

After arthroplasty treatment, some complications commonly occur, such as early revision, infection/dislocation, and venous thromboembolism (VTE). This study aims to use a network meta-analysis to compare effects of 9 anticoagulant drugs (edoxaban, dabigatan, apixaban, rivaroxaban, warfarin, heparin, bemiparin, ximelagatran, and enoxaparin) in preventing postoperative complications in arthroplasty patients.. After retrieving PubMed, Embase, and Cochrane Library database from the inception to November 2016, randomized controlled trials were enrolled. The integration of direct and indirect evidences was performed to calculate odd ratios and the surface under the cumulative ranking curves. Nineteen eligible randomized controlled trials were included.. The network meta-analysis results showed that compared with warfarin, edoxaban, apixaban, and rivaroxaban had a lower incidence rate in asymptomatic deep venous thrombosis, which indicated that edoxaban, apixaban, and rivaroxaban had better effects on prevention. Similarly, in comparison to enoxaparin, edoxaban and rivaroxaban had better effect; rivaroxaban was better than ximelagatran in preventive effects. Compared with apixaban, edoxaban, dabigatan, rivaroxaban, and enoxaparin had a higher incidence rate in clinically relevant non-major bleeding, which showed that preventive effects were relatively poor. In addition, the results of the surface under the cumulative ranking curves showed that rivaroxaban and bemiparin worked best on symptomatic deep venous thrombosis and pulmonary embolism. In terms of bleeding, apixaban and warfarin had better preventive effects.. Our findings suggested that rivaroxaban may work better in terms of symptomatic deep venous thrombosis and pulmonary embolism, whereas apixaban had better preventive effects in bleeding.

Topics: Anticoagulants; Arthroplasty; Azetidines; Benzylamines; Dabigatran; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism; Warfarin

Enzalutamide, a novel, oral androgen receptor antagonist used for the treatment of metastatic, castration-resistant prostate cancer, has been shown to improve overall and progression-free survival, prolong time to initiation of chemotherapy, reduce skeletal-related events, and carry a favorable adverse effect profile. Metastatic prostate cancer is a disease of older men, a population with an increased incidence of medical comorbidities warranting anticoagulation. Prostate cancer itself, along with some of its therapies, is also prothrombotic. Enzalutamide interacts with several anticoagulants through various mechanisms, making their concurrent use clinically challenging. As such, complex decisions about anticoagulation in these patients are frequently encountered by treating physicians. In this review, we describe the potential interactions between enzalutamide and various anticoagulants, and suggest management paradigms based on the current body of knowledge for patients with atrial fibrillation, venous thromboembolism, and mechanical heart valves.

Topics: Androgen Receptor Antagonists; Anticoagulants; Atrial Fibrillation; Benzamides; Dabigatran; Drug Interactions; Embolism; Heart Valve Prosthesis; Heparin, Low-Molecular-Weight; Humans; Male; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

Currently, little evidence is available on the length and type of anticoagulation used for extended treatment for prevention of recurrent venous thromboembolism (VTE) in patients with unprovoked VTE who have completed initial oral anticoagulation therapy.. To compare the efficacy and safety of available oral therapeutic options (aspirin, warfarin, direct oral anticoagulants (DOACs)) for extended thromboprophylaxis in adults with a first unprovoked VTE, to prevent VTE recurrence after completion of an acceptable initial oral anticoagulant treatment period, as defined in individual studies.. For this review, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (March 2017) as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). We also searched trials registries (March 2017) and reference lists of relevant articles.. We included randomised controlled trials in which patients with a first, symptomatic, objectively confirmed, unprovoked VTE, who had been initially treated with anticoagulants, were randomised to extended prophylaxis (vitamin K antagonists (VKAs), antiplatelet agents, or DOACs) versus no prophylaxis or placebo. We also included trials that compared one type of extended prophylaxis versus another type of extended prophylaxis.. Two review authors independently selected studies, assessed quality, and extracted data. We resolved disagreements by discussion.. Six studies with a combined total of 3436 participants met the inclusion criteria. Five studies compared extended prophylaxis versus placebo: three compared warfarin versus placebo, and two compared aspirin versus placebo. One study compared one type of extended prophylaxis (rivaroxaban) versus another type of extended prophylaxis (aspirin). For extended prophylaxis versus placebo, we downgraded the quality of the evidence for recurrent VTE and all-cause mortality to moderate owing to concerns arising from risks of selection and performance bias in individual studies. For all other outcomes in this review, we downgraded the quality of the evidence to low owing to concerns arising from risk of bias for the studies stated above, combined with concerns over imprecision. For extended prophylaxis versus other extended prophylaxis, we downgraded the quality of the evidence for recurrent VTE and major bleeding to moderate owing to concerns over imprecision. Risk of bias in the individual study was low.Meta-analysis showed that extended prophylaxis was no more effective than placebo in preventing VTE-related mortality (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.14 to 6.98; 1862 participants; 4 studies; P = 0.98; low-quality evidence), recurrent VTE (OR 0.63, 95% CI 0.38 to 1.03; 2043 participants; 5 studies; P = 0.07; moderate-quality evidence), major bleeding (OR 1.84, 95% CI 0.87 to 3.85; 2043 participants; 5 studies; P = 0.86; low-quality evidence), all-cause mortality (OR 1.00, 95% CI 0.63 to 1.57; 2043 participants; 5 studies; P = 0.99; moderate-quality evidence), clinically relevant non-major bleeding (OR 1.78, 95% CI 0.59 to 5.33; 1672 participants; 4 studies; P = 0.30; low-quality evidence), stroke (OR 1.15, 95% CI 0.39 to 3.46; 1224 participants; 2 studies; P = 0.80; low-quality evidence), or myocardial infarction (OR 1.00, 95% CI 0.35 to 2.87; 1495 participants; 3 studies; P = 1.00; low-quality evidence).One study showed that the novel oral anticoagulant rivaroxaban was associated with fewer recurrent VTEs than aspirin (OR 0.28, 95% CI 0.15 to 0.54; 1389 participants; P = 0.0001; moderate-quality evidence). Data show no clear differences in the incidence of major bleeding between rivaroxaban and aspirin (OR 3.06, 95% CI 0.37 to 25.51; 1389 participants; P = 0.30; moderate-quality evidence) nor in the incidence of clinically relevant non-major bleeding (OR 0.84, 95% CI 0.37 to 1.94; 1389 participants; 1 study; P = 0.69; moderate-quality evidenc. Evidence is currently insufficient to permit definitive conclusions concerning the effectiveness and safety of extended thromboprophylaxis in prevention of recurrent VTE after initial oral anticoagulation therapy among participants with unprovoked VTE. Additional good-quality large-scale randomised controlled trials are required before firm conclusions can be reached.

Topics: Administration, Oral; Anticoagulants; Aspirin; Hemorrhage; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Secondary Prevention; Stroke; Venous Thromboembolism; Warfarin

Appropriate treatment of venous thromboembolism (VTE) is critical to minimizing long-term morbidity and mortality. The emergence of direct oral anticoagulants (DOACs) has provided clinicians with expanded therapeutic options for patients with VTE, and as a result, updated practice guidelines released by the American College of Chest Physicians favor DOACs over traditional anticoagulants, such as warfarin. The newest DOAC, betrixaban, received FDA approval in 2017, with an indication for VTE prophylaxis in hospitalized adults. Additionally, results from the XALIA study on the real-world outcomes of rivaroxaban are now available. A reversal agent for dabigatran, idarucizumab, also received FDA approval in 2017, and other reversal agents are in development. This article will provide an overview of current VTE treatment strategies, with an emphasis on the place in therapy of the DOACs.

Topics: Administration, Oral; Anticoagulants; Benzamides; Dabigatran; Female; Humans; Incidence; Male; Prognosis; Pyridines; Risk Assessment; Rivaroxaban; Severity of Illness Index; Survival Rate; Treatment Outcome; Venous Thromboembolism; Warfarin

Recent findings require an update of previous recommendations for the perioperative use of Direct Oral AntiCoagulants (DOACs). A break in preoperative treatment of 24-96 hours is recommended based on the pharmacokinetic profiles of DOACs and depends on individual patient characteristics, their renal and possibly liver function, and their surgery-related risk of bleeding. In cases of renal or hepatic insufficiency, whether to extend the preoperative interruption of IIa- and Xa-inhibitors is a clinical decision that must be reached on an individual patient basis. In cases of epidural or spinal anaesthesia, more conservative pausing-intervals are recommended due to the risk of persistent neurologic deficits (e.g., paraplegia) following the development of spinal subdural and epidural haematomas. Elective surgery should be postponed according to these recommendations. Preoperative "bridging" with LMWH (more precisely referred to as "switching") should be omitted due to a significantly increased risk of bleeding. In addition, the incidence of perioperative thromboembolic risks, such as DVT, PE, and stroke, are no different whether interruption or "switching" is undertaken. Postoperatively, the DOACs can be reinstituted within the first 24 hours. In cases of major surgery or if there is a higher risk of bleeding, resumption of DOACS should only begin after 24-72 hours. In patients with an elevated thromboembolic risk, transient postoperative LMWH administration can be recommended during this period.Interaction of DOACs with other drugs usually occurs during the absorption, transport and elimination of these drugs. Therefore, substance- specific restrictions and recommendations should be observed during these times. In everyday clinical practice, webbased, independent information portals on drug-interactions are very helpful in providing safe and rapid information about potential interactions when DOACs are used in combination with other drugs, especially during perioperative management.Non-adherence to medications is a worldwide problem that has dangerous and costly consequences. Present data suggest that persistence is the primary factor that supports adherence. Despite the adherence data presented in the DOACS approval studies (e.g., persistence in the treatment of acute venous thromboembolism has been reported to be between 94-99%), the first registries and meta-analyses provide sobering results regarding the incidence of persistence and the success rate of i. Aktuelle Erkenntnisse erfordern die Aktualisierung früherer Empfehlungen zum perioperativen Einsatz von direkte orale Antikoagulanzien (DOAKs). Auf Grundlage der pharmakokinetischen Profile wird in Abhängigkeit von Nierenfunktion, ggf. Leberfunktion sowie individuellem und eingriffsspezifischem Blutungsrisiko eine präoperative Pausierung von 24–96 Stunden in Abhängigkeit von dem verwendeten DOAK empfohlen. Bei schwerer Nieren- oder Leberinsuffizienz ist es eine individuelle, klinische Entscheidung, die präoperative Pause für die Xa-inhibitoren zu verlängern. Für Patienten mit rückenmarksnahen Regionalanästhesieverfahren gelten aufgrund des Risikos von spinal sub- und epiduralen Hämatomen und dem Risiko bleibender schwerer neurologischer Defizite (Querschnittslähmung) sehr konservative Intervalle im oberen Pausierungsbereich. Ein bereits präoperativ beginnendes „Bridging” mit NMH (eigentlich „Switching”) sollte wegen signifikant erhöhter Blutungsrisiken unterbleiben. Das perioperative Thromboembolierisiko (z.B. Thrombose, Lungenembolie, Hirninfarkt) ist nach einer präoperativen Pause bzw. einem präoperativen „Switching” nicht unterschiedlich. Postoperativ können DOAKs innerhalb von 24 h, nach größeren Eingriffen bzw. höherem Blutungsrisiko erst nach 24–72 Stunden wiederaufgenommen werden. Eine postoperative, passagere Umstellung auf eine NMH-Gabe („Switching”) bei erhöhtem venösem Thromboembolierisiko kann in diesem Zeitraum erfolgen.Medikamenteninteraktionen von direkten oralen Antikoagulanzien treten meist bei der Absorption, beim Transport und bei der Elimination von anderen Medikamenten auf. Hierbei sind substanzspezifische Einschränkungen und Empfehlungen zu beachten. Um im klinischen Alltag eine sichere und schnelle Information, auch über DOAKs in Kombination mit anderen Medikamenten im perioperativen Management, zu erhalten, sind webbasierte, unabhängige Informationsportale sehr hilfreich.Die Non-Adhärenz von Medikamenten ist weltweit verbreitet, ist gefährlich und teuer in ihren Folgen. Die aktuellen Daten beschreiben vorwiegend die Persistenz als ein orientierendes Maß für die Adhärenz. Unabhängig von den Zulassungsstudien der DOAKs (Persistenz bei der Therapie akuter venöser Thromboembolien zwischen 94 – 99%) liefern erste Register und Metaanalysen ernüchternde Ergebnisse zur Persistenz und zur Verbesserung der Adhärenz der DOAKs in der Langzeitanwendung.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Drug Interactions; Drug Substitution; Heparin, Low-Molecular-Weight; Humans; Kidney Function Tests; Liver Function Tests; Metabolic Clearance Rate; Perioperative Care; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Thiazoles; Venous Thromboembolism

New oral anticoagulants (NOACs) are likely to have a major impact in the next few years, changing clinical practice of anticoagulation therapy. Evidence on its efficacy and superiority to vitamin K antagonists (VKAs) in treating non-cancer patients have been reported in a few clinical trials. However, patients with cancer are complicated by the prothrombotic nature of the disease, need for potentially invasive surgery and interventions, and altered drug handling. This chapter examines the available evidence and guidelines on the use of NOAC in patients with cancer.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Catheters, Indwelling; Dabigatran; Drug Administration Schedule; Drug Dosage Calculations; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Pulmonary embolism (PE) affects >600,000 patients per year in the United States. Evaluation includes clinical decision rules, laboratory tests, and several imaging modalities. The diagnosis of PE has risen in recent years, particularly subsegmental PE (SSPE). Controversy exists concerning the diagnosis and treatment of these lesions.. We sought to provide emergency physicians with a review of the controversies surrounding PE testing and the diagnosis and treatment of SSPE.. With the rise of computed tomography (CT) testing for PE, diagnosis has increased. Providers often omit risk stratification in favor of D-dimer or imaging, which does not have literature support. The detection of PE has risen by 80%, and this increased testing is associated with several risks, including contrast reaction, nephropathy, and increased radiation. SSPE diagnosis has risen with improved imaging technology, but the literature shows low interobserver agreement with diagnosis of true SSPE. Studies disagree on the clinical significance and dangers of this PE subset. The American College of Chest Physicians 2016 guidelines recommend withholding anticoagulation for SSPE with low risk for recurrent thrombus and no concurrent deep vein thrombosis. Patients at high risk for recurrent venous thromboembolism or with deep vein thrombosis warrant anticoagulation. The provider is ultimately responsible for appropriate evaluation with risk stratification and selective testing.. SSPE presents a quandary, because the literature differs in showing harm despite increased diagnosis. American College of Chest Physicians guidelines for the treatment of SSPE take into account the patient, the imaging, and other imaging modalities. Providers should use risk stratification with shared decision-making in the evaluation and treatment of SSPE.

Topics: Anticoagulants; Dabigatran; Decision Making; Humans; Patient Outcome Assessment; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles; Tomography, X-Ray Computed; Venous Thromboembolism

Venous thromboembolism (VTE) is a common and potentially fatal complication of arthroplasty.. We reviewed randomized trials to determine which anticoagulant has the best safety and efficacy in hip and knee arthroplasty patients. We searched PubMed, MEDLINE, and EMBASE through January 2016.. Compared to enoxaparin (most commonly dosed 40 mg once daily), the relative risk (RR) of VTE was lowest for edoxaban 30 mg once daily (0.49; 95% confidence interval [CI], 0.32-0.75), fondaparinux 2.5 mg once daily (0.53; 95% CI, 0.45-0.63), and rivaroxaban 10 mg once daily (0.55; 95% CI, 0.46-0.66), and highest for dabigatran 150 mg once daily (1.19; 95% CI; 0.98-1.44). The RR of major/clinically relevant bleeding was lowest for apixaban 2.5 mg twice daily (0.84; 95% CI; 0.70-0.99) and highest for rivaroxaban (1.27; 95% CI, 1.01-1.59) and fondaparinux (1.64; 95% CI, 0.24-11.35). Fondaparinux was the only agent that was more effective than enoxaparin 30 mg twice daily (VTE RR = 0.58; 95% CI, 0.43-0.76).. With the possible exception of apixaban, newer anticoagulants that lower the risk of postoperative VTE increase bleeding.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Dabigatran; Enoxaparin; Fondaparinux; Hemorrhage; Humans; Morpholines; Polysaccharides; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Incomplete thrombus resolution in patients with venous thromboembolism (VTE) may increase the risk of recurrent thromboembolic events and other complications, such as post-thrombotic syndrome. Various options exist for thrombus resolution, including systemic thrombolytic agents, catheter-directed thrombolysis, and traditional anticoagulants such as heparins or vitamin K antagonists (VKAs). Data are accumulating on the use of non-VKA oral anticoagulants, such as rivaroxaban, and these may provide greater thrombus resolution compared with VKAs. Data from the phase III rivaroxaban studies presented here show that a 21-day intensive dosing regimen of rivaroxaban 15 mg twice daily is effective during the acute treatment phase for VTE, with similar recurrence rates and thrombus resolution to standard anticoagulation. Pooled analyses of phase III studies have also indicated that rivaroxaban 20 mg once daily monotherapy for up to 12 months after this initial intensive treatment period may provide effective prevention of recurrent VTE and a reduction in the risk of major bleeding, irrespective of clot burden. Four case studies from the Darmstadt Academic Teaching Hospital, Germany, and Gunma University Hospital, Japan, are also provided. Further clinical studies and real-world data may improve our understanding of initial intensive dose regimens, and assess the full significance of thrombus burden in VTE.

Topics: Aged; Aged, 80 and over; Factor Xa Inhibitors; Female; Humans; Male; Multidetector Computed Tomography; Recurrence; Rivaroxaban; Ultrasonography; Venous Thromboembolism; Young Adult

Approximately 900,000 people are affected by some sort of venous thromboembolic (VTE) event every year in the United States. VTE diagnosis used to mean treatment with medications that required routine lab monitoring for safety and efficacy. Activated factor X (FXa) inhibition has emerged as a convenient pathway for management of VTE and currently three FXa inhibitors are available for anticoagulation management - rivaroxaban, apixaban, and edoxaban. Continued development of medications utilizing this pathway may offer advantages via novel pharmacokinetic or pharmacodynamic properties that may minimize the adverse effects associated with traditional anticoagulant therapy. This review summarizes the available information regarding pharmacokinetic, pharmacodynamic, and early safety and efficacy data for three factor Xa inhibitors being developed - darexaban, betrixaban and nokxaban. The studies reviewed in this article suggests that three newer agents possess the potential for promise based on early phase I and II trials.

Topics: Administration, Oral; Animals; Azepines; Benzamides; Blood Coagulation; Drug Discovery; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are effective in preventing and treating venous thromboembolism, and preventing stroke in atrial fibrillation. Until recently, there has been no specific reversal agent for DOACs. Now, a specific antidote for the direct thrombin inhibitor, dabigatran has been approved for use, and antidotes for factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are being developed. We review the evidence for currently used and emerging reversal strategies, and discuss possible clinical implications, including increased prescription of DOACs, use of DOACs in clinical situations previously felt to pose too great a risk of bleeding, and use of reversal agents beyond currently approved indications.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antithrombins; Arginine; Dabigatran; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Humans; Piperazines; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Thiazoles; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are increasingly used for prevention and treatment of venous thromboembolism and for prevention of stroke in patients with nonvalvular atrial fibrillation. In phase III clinical trials that included more than 100,000 patients, the DOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with less serious bleeding, particularly less intracranial bleeding. Real-world evidence supports these outcomes. Despite this, some physicians and patients are concerned about serious bleeding or emergencies unless specific reversal agents for the DOACs are available. However, in clinical trials performed without reversal agents, the outcome of major bleeds was similar or better in patients receiving DOACs than in those taking VKAs. Because of their short half-lives, supportive measures are sufficient to manage most bleeds in patients receiving DOACs. Anticoagulant reversal should only be considered with life-threatening bleeds, with bleeds that fail to respond to usual measures and in patients requiring urgent surgery. Idarucizumab is licensed for dabigatran reversal and andexanet alfa is likely to be soon licensed for reversal of rivaroxaban, apixaban, and edoxaban. To ensure responsible use of these agents, every hospital needs a bleeding management algorithm that identifies patients eligible for reversal and outlines appropriate dosing regimens.

Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa; Forecasting; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism

Current evidence indicates that heart failure (HF) confers a hyper-coagulable state that is associated with adverse events including stroke, systemic embolism, and mortality. This may be due to the elevated levels of pro-thrombotic and pro-inflammatory cytokines that are seen in patients with acute and chronic HF. Left ventricular wall motion abnormalities in patients with systolic dysfunction predispose to local thrombosis due to blood stasis as does atrial fibrillation (AF) which leads to blood stasis in regions of the atria. The high risk of thromboemboli in HF patients with AF has resulted in the use anticoagulation therapy to prevent the occurrence of catastrophic events. There is evidence, however, that the pro-inflammatory, pro-thrombotic state that exists in HF puts patients who are in sinus rhythm at risk. The novel oral anticoagulants (NOACs) have been shown in RCT to have at least equivalent efficacy in reducing stroke as warfarin while exposing patients to a lower risk of bleeding. The fact that the NOACs don't require routine monitoring to assure that patients remain within the therapeutic range and have relatively simple dosing requirements and a safer risk profile makes them attractive substitutes to warfarin in HF patients with atrial fibrillation and other conditions (e.g. deep venous thrombosis). Post hoc analyses from a subset of HF patients from the RCTs in AF patients have demonstrated similar findings as were reported in the entire populations that were included in the trials. As a result, NOACS are commonly used now in HF patients with AF. For HF patients with reduced ejection fraction in sinus rhythm, the use of warfarin in randomized clinical trials (RCT) to reduce stroke has been disappointing and associated with increase bleeding risk when compared to aspirin. The advantages of the NOACs over warfarin, however, raise the question of whether they might improve outcomes in HF patients who are in sinus rhythm. The currently ongoing COMMANDER-HF trial has been designed to address this issue. In this chapter we review evidence of existence of a prothombotic state in HF, the pharmacodynamics and clinical trials of the NOACs and the outcomes from NOAC substudies in the HF subgroup. We also discuss the rationale for using anticoagulation in HF independent of arrhythmia burden.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Heart Failure; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin

Emergency physicians make treatment decisions in patients who present to the emergency department (ED) with acute venous thromboembolism (VTE). They also encounter patients on target-specific oral anticoagulants (TSOACs) who require urgent intervention. New approvals and increasing prescriptions for TSOACs (e.g., apixaban, dabigatran, edoxaban, and rivaroxaban) for the management of several thromboembolic disorders warrant an evaluation of the impact of these agents in the ED setting.. This review discusses the use of TSOACs in the ED for the treatment of acute VTE, and highlights strategies for the management of patients on TSOACs who present to the ED with other complications, such as bleeding complications or requiring emergency surgery.. Apixaban, dabigatran, edoxaban, and rivaroxaban have been approved for the treatment of acute VTE. We discuss the impact of this on ED management of TSOAC-naïve patients and highlight results with TSOACs in high-risk subgroups including the elderly and those with prior VTE or active cancer. This review also discusses management strategies for patients on TSOACs. For emergency physicians, strategies for the management of bleeding, approaches to patient care when emergency surgery is needed, laboratory assays for measuring plasma concentrations of TSOACs, and drug-drug interactions are of special importance.. Familiarity with TSOACs will better position emergency physicians to provide state-of-the art care to their patients with VTE and help them manage potentially complicated circumstances related to the chronic use of these drugs.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Blood Coagulation Tests; Dabigatran; Drug Interactions; Drug Monitoring; Emergency Service, Hospital; Factor Xa Inhibitors; Hemorrhage; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

Despite widespread diffusion of pharmacological prophylaxis, deep venous thrombosis (DVT) is still a common cause of morbidity after major orthopedic surgery (total hip replacement--THR--and total knee replacement--TKR). At present, clear evidence has been provided that pharmacological primary prophylaxis with low molecular weight heparin (LMWH) is associated with a significant decrease in the incidence of venous thromboembolism. The main limitation of LMWH prophylaxis however is the need for parenteral administration with a not negligible drop-out of treatment. Newer oral anticoagulants (NAOs) dabigatran, rivaroxaban, apixiban and edoxaban may be valid alternatives in elective surgery. Several studies have demonstrated the efficacy and safety of NAOs after THR and TKR. The research for new compounds and their antidote is under continuous development Aim of this paper was to review the indications and clinical results of DVT prophylaxis with NAO in patients undergoing major orthopaedic surgery.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Enoxaparin; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Polysaccharides; Rivaroxaban; Venous Thromboembolism

To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products.. Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information.. Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions.. The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy.. The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Drug Interactions; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

To assess the cost-effectiveness of apixaban versus rivaroxaban, low-molecular-weight heparin (LMWH)/dabigatran, and LMWH/vitamin K antagonist (VKA) for the initial treatment and prevention of recurrent thromboembolic events in patients with venous thromboembolism (VTE).. A Markov model was developed to evaluate the pharmacoeconomic effect of 6 months of treatment with apixaban versus other anticoagulants over a lifetime horizon. Network meta-analyses were conducted using the results of the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy (AMPLIFY), EINSTEIN-pooled, and RE-COVER I and II trials for the following end points: recurrent VTE, major bleeds, clinically relevant non-major bleeds, and treatment discontinuations. The analysis was conducted from the perspective of the United Kingdom National Health Service. The outcomes evaluated were the number of events avoided in a 1000-patient cohort, total costs, life years, quality-adjusted life years (QALYs), and cost per QALY gained over a patient's lifetime.. Treatment for 6 months with apixaban was projected to result in fewer recurrent VTE and bleeding events in comparison to rivaroxaban, LMWH/dabigatran, and LMWH/VKA. Apixaban was cost-effective compared with LMWH/VKA at an incremental cost-effectiveness ratio of £2520 per QALY gained and was a dominant (ie, lower costs and higher QALYs) alternative to either rivaroxaban or LMWH/dabigatran. Sensitivity analysis indicated that results were robust over a wide range of inputs.. The assessment of the effects and costs of apixaban in this study predicted that apixaban is a dominant alternative to rivaroxaban and LMWH/dabigatran and a cost-effective alternative to LMWH/VKA for 6 months of treatment of VTE and the prevention of recurrence.

Topics: Anticoagulants; Cost-Benefit Analysis; Dabigatran; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Secondary Prevention; United Kingdom; Venous Thromboembolism

In recent years, small oral compounds that specifically block activated coagulation factor X (FXa) or thrombin (FIIa) have become alternatives to the anticoagulants that had been used for several decades. As of today, these direct oral anticoagulants (DOACs) include dabigatran etexilate (thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (inhibitors of FXa). While there is no doubt that DOACs represent a major step forward in the management of patients with venous thromboembolic disease and atrial fibrillation, new challenges have arisen. They need to be addressed with the necessary pragmatism on the basis of evidence. Indeed, a better understanding of the management of these last-generation antithrombotics will favour safer use and increase confidence of the practitioner for the prescription of these drugs. The aim of this article is to present practical suggestions for the prescription and use of these drugs in everyday clinical practice, based on clinical experience and recently updated recommendations of the European Heart Rhythm Association and the American College of Chest Physicians among other scientific organisations. We address issues such as pharmacokinetics, dosing, side effects, limitations of use, drug interactions, switching from and to other anticoagulants, renal function, concomitant administration of antiplatelet agents and perioperative use. We also address the issue of monitoring and reversal, taking advantage of the most recent development in this latter area. Rather than being one additional set of recommendations, our narrative review aims at assisting the practicing physician in his or her daily handling of these novel anticoagulant compounds, based on frequently asked questions to the authors, a group of experienced specialists in the field who have, however, no commitment to issue guidelines.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Humans; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Recurrence; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism

Venous thromboembolism (VTE) is the most widespread severe complication after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We conducted this meta-analysis to further validate the benefits and harms of rivaroxaban use for thromboprophylaxis after THA or TKA. We thoroughly searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Trial sequential analysis (TSA) was applied to test the robustness of our findings and to obtain a more conservative estimation. Of 316 articles screened, nine studies were included. Compared with enoxaparin, rivaroxaban significantly reduced symptomatic VTE (P = 0.0001) and symptomatic deep vein thrombosis (DVT; P = 0.0001) but not symptomatic pulmonary embolism (P = 0.57). Furthermore, rivaroxaban was not associated with an increase in all-cause mortality, clinically relevant non-major bleeding and postoperative wound infection. However, the findings were accompanied by an increase in major bleeding (P = 0.02). The TSA demonstrated that the cumulative z-curve crossed the traditional boundary but not the trial sequential monitoring boundary and did not reach the required information size for major bleeding. Rivaroxaban was more beneficial than enoxaparin for preventing symptomatic DVT but increased the risk of major bleeding. According to the TSA results, more evidence is needed to verify the risk of major bleeding with rivaroxaban.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Dabigatran; Drug Interactions; Humans; Outpatients; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency, Chronic; Rivaroxaban; Thiazoles; Venous Thromboembolism

Gender differences have been reported in patients with acute VTE treated with antithrombotic drugs.. To address the relationship between gender and new oral anticoagulants (NOACs), we performed a meta-analysis to evaluate the incidence of recurrent VTE and major plus clinically relevant non-major bleedings in males and females, with acute VTE, treated with NOACs over the treatment period.. Systematic review and meta-analysis of double blind randomized controlled trials (RCTs).. MEDLINE, Cochrane Library of Clinical Trials (up to September 2015).. RCTs that compared the beneficial and harmful effects of NOAC drugs (apixaban, dabigatran, edoxaban and rivaroxaban).. Three authors abstracted data. Study-specific risk ratios (RR) were combined using random-effects model.. Nine studies including 16,372 patients were selected. No significant difference for the incidence of recurrent VTE was found between men and women. Compared to men, women had a higher incidence of major bleedings plus clinically relevant minor bleedings (5.3% and 7.9% respectively; RR: 0.635; 95% CI: 0.54-0.74; p<0.001). The subgroup analysis showed a significant gender difference in incidence of major bleedings and clinically relevant minor bleedings only for Edoxaban (RR: 0.52; 95% CI: 0.42-0.64; p<0.001).. This meta-analysis showed, compared to men, a higher risk of bleeding in women with acute VTE treated with NOACs. Future trials should evaluate the effect of gender on bleeding in patients with acute VTE treated with NOACs.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Double-Blind Method; Female; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Sex Characteristics; Thiazoles; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Male; Middle Aged; Phlebography; Prognosis; Pulmonary Embolism; Pyridines; Randomized Controlled Trials as Topic; Rivaroxaban; Severity of Illness Index; Survival Analysis; Thiazoles; Treatment Outcome; Venous Thromboembolism

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

Topics: Anticoagulants; Dabigatran; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Time Factors; Venous Thromboembolism; Warfarin

Half of all patients with acute venous thromboembolism are aged over 70 years; they then face the added hazard of an age-related increase in the incidence of major bleeding. This makes it even more important to weigh the balance of benefit and risk when considering anticoagulant treatment and treatment duration. Traditional treatment with a heparin (usually low molecular weight) followed by a vitamin K antagonist such as warfarin is effective but is often complicated, especially in the elderly. The direct-acting oral anticoagulants (DOACs), i.e. the thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, are given in fixed doses, do not need laboratory monitoring, have fewer drug-drug interactions and are therefore much easier to take. Randomised trials, their meta-analyses and 'real-world' data indicate the DOACs are no less effective than warfarin (are non-inferior) and probably cause less major bleeding (especially intracranial). It seems the relative safety of DOACs extends to age above 65 or 70 years, although bleeding becomes more likely regardless of the chosen anticoagulant. Renal impairment, comorbidities (especially cancer) and interventions are special hazards. Ways to minimise bleeding include patient selection and follow-up, education about venous thromboembolism, anticoagulants, drug interactions, regular checks on adherence and avoiding needlessly prolonged treatment. The relatively short circulating half-lives of DOACs mean that time, local measures and supportive care are the main response to major bleeding. They also simplify the management of invasive interventions. An antidote for dabigatran, idarucizumab, was recently approved by regulators, and a general antidote for factor Xa inhibitors is in advanced development.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Clinical Trials as Topic; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Hemorrhage; Humans; Practice Guidelines as Topic; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Warfarin

Four non-vitamin K antagonist oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) have been approved in the United States for treatment of atrial fibrillation (AF) and venous thromboembolic disease. They have been as or more effective than the prior standards of care, with less fatal or intracranial bleeding, fewer drug and dietary interactions, and greater patient convenience. Nonetheless, the absence of the ability for clinicians to assess compliance or washout with a simple laboratory test (or to adjust dosing with a similar assessment) and the absence of an antidote to rapidly stop major hemorrhage or to enhance safety in the setting of emergent or urgent surgery/procedures have been limitations to greater non-vitamin K antagonist oral anticoagulant usage and better thromboembolic prevention. Accordingly, a Cardiac Research Safety Consortium "think tank" meeting was held in February 2015 to address these concerns. This manuscript reports on the discussions held and the conclusions reached at that meeting.

Topics: Antibodies, Monoclonal, Humanized; Antidotes; Antithrombins; Arginine; Atrial Fibrillation; Congresses as Topic; Dabigatran; Drug Monitoring; Factor Xa; Factor Xa Inhibitors; Humans; Partial Thromboplastin Time; Piperazines; Product Surveillance, Postmarketing; Pyrazoles; Pyridines; Pyridones; Recombinant Proteins; Rivaroxaban; Stroke; Thiazoles; Thrombin Time; Venous Thromboembolism

Historically, warfarin or aspirin have been the recommended therapeutic options for the extended treatment (>3 months) of VTE. Data from Phase III randomised controlled trials (RCTs) are now available for non-VKA oral anticoagulants (NOACs) in this indication. The current systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of anticoagulants for the extended treatment of VTE.. Electronic databases (accessed July 2014 and updated April 2016) were systematically searched to identify RCTs evaluating apixaban, aspirin, dabigatran, edoxaban, rivaroxaban, and warfarin for the extended treatment of VTE. Eligible studies included adults with an objectively confirmed deep vein thrombosis, pulmonary embolism or both. A fixed-effect Bayesian NMA was conducted, and results were presented as relative risks (RRs). Sensitivity analyses examining (i) the dataset employed according to the time frame for outcome assessment (ii) the model used for the NMA were conducted.. Eleven Phase III RCTs (examining apixaban, aspirin, dabigatran, rivaroxaban, warfarin and placebo) were included. The risk of the composite efficacy outcome (VTE and VTE-related death) was statistically significantly lower with the NOACs and warfarin INR 2.0-3.0 compared with aspirin, with no significant differences between the NOACs. Treatment with apixaban (RR 0.23, 95% CrI 0.10, 0.55) or dabigatran (RR 0.55, 95% Crl 0.43, 0.71) was associated with a statistically significantly reduced risk of 'major or clinically relevant non-major bleed' compared with warfarin INR 2.0-3.0. Apixaban also showed a significantly reduced risk compared with dabigatran (RR 0.42, 95% Crl 0.18, 0.97) and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59). Sensitivity analyses indicate that results were dependent on the dataset, but not on the type of NMA model employed.. Results from the NMA indicate that NOACs are an effective treatment for prevention of VTE or VTE-related death) in the extended treatment setting. However, bleeding risk differs between potential treatments, with apixaban reporting the most favourable profile compared with other NOACs, warfarin INR 2.0-3.0, and aspirin.

Topics: Administration, Oral; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Long-Term Care; Network Meta-Analysis; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are rapidly replacing vitamin K antagonists (VKAs) for treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. When compared with conventional VTE treatment consisting of a parenteral anticoagulant followed by a VKA, the DOACs were equally effective for prevention of recurrence, but were associated with less bleeding. With similar efficacy, better safety, and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. Nonetheless, measures are needed to optimize the safety of DOACs. Focusing on these measures, this paper summarizes the results of phase III trials evaluating DOACs for VTE treatment; identifies which VTE patients are or are not candidates for DOACs; provides guidance on how to choose among DOACs; lists the licensed dosing information for DOACs; discusses the optimal treatment duration for VTE; describes periprocedural management of DOACs in patients requiring surgery or intervention; and finally, reviews the management of bleeding, including the role for specific reversal agents.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Clinical Trials, Phase III as Topic; Coagulants; Dabigatran; Humans; Patient Safety; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

Anticoagulation therapy is common in thoracic transplant recipients. Direct oral anticoagulants (DOACs) are alternatives to warfarin therapy, but characterization of their use in solid organ transplant is absent.. The primary objective of this study was to describe a thoracic transplant patient population initiated on DOAC therapy. Secondary objectives were to assess adverse reactions, venous thromboembolism (VTE) recurrence, and drug-drug interactions during DOAC therapy.. Single-center retrospective cohort study.. A tertiary care medical center including inpatient hospitalization and outpatient transplant clinic visits.. Thoracic transplant recipients who were initiated on DOACs between May 1, 2011, and March 1, 2015, at the University of Pittsburgh Medical Center were included.. A total of 37 patients were included in the analysis. A majority of the patients were lung transplant recipients (86.4%) with a median age of 60.7 years. Twenty-eight patients had a history of VTE. The primary indication for DOAC initiation was VTE (86.5%). Rivaroxaban (78.4%) was the most commonly utilized agent. Dose reductions for major drug interactions (37.8%), renal insufficiency (10.8%), or both (8.1%) occurred within the study. Two patients had breakthrough VTE during DOAC therapy. Eight bleeding events were reported in the cohort, one of which was considered a major bleed. There was no difference in the incidence of bleeding in patients with drug-drug interactions and without drug-drug interactions during DOAC therapy (26.0% vs 7.1%, P = .154).. Direct oral anticoagulant therapy was well tolerated by thoracic transplant recipients. Drug interactions and renal dose adjustments were common.

Topics: Anticoagulants; Heart Transplantation; Humans; Lung Transplantation; Middle Aged; Retrospective Studies; Rivaroxaban; Transplant Recipients; Venous Thromboembolism

Traditional anticoagulants, such as low-molecular-weight heparin and vitamin K antagonists, have been the mainstay for the treatment of venous thromboembolism (VTE) in the hospital setting and after discharge. These anticoagulants are effective but are associated with some limitations that may lead to their underuse. Based on the results of the EINSTEIN clinical trial program, the oral, direct factor Xa inhibitor rivaroxaban is approved for the treatment of acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and for the prevention of recurrent VTE. The single-drug approach with rivaroxaban is now available in both the hospital and the outpatient settings and may overcome some of the limitations of traditional agents. This review provides hospital physicians with an overview of the practical management of rivaroxaban and a critical evaluation of its use for the treatment of DVT and PE, including in specific clinical settings and special patient populations.

Topics: Factor Xa Inhibitors; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

In studying the comparative effectiveness of novel oral anticoagulants (NOACs) in orthopedic surgery and in non-valvular atrial fibrillation, previous meta-analyses have found no proof of difference in head-to-head indirect comparisons between individual agents. However, the question of their therapeutic equivalence remains unanswered.. The objective of this analysis was to test the equivalence of three NOACs (dabigatran, rivaroxaban, apixaban) in orthopedic surgery and four NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) in non-valvular atrial fibrillation.. Standard pairwise meta-analysis and network meta-analysis for indirect comparisons were combined with equivalence testing. The endpoint was venous thromboembolism in orthopedic surgery and a composite of stroke or systemic embolism in atrial fibrillation. Comparisons were expressed as risk difference (RD). Margins for equivalence testing were derived from the original trials.. Our results indicate that rivaroxaban and apixaban (but not dabigatran) are equivalent for thromboprophylaxis in orthopedic surgery. In atrial fibrillation, all the four NOACs we tested were found to meet the criterion of therapeutic equivalence. Some concern, however, is raised by some findings focused on adverse events of these agents, in which the equivalence was not proven in all analyses.. Regardless of clinical implications, our results can be the basis to develop local acquisition tenderings on NOACS. In Italy, a new law has been issued according to which equivalence analyses have become a mandatory prerequisite for local tenderings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation; Dabigatran; Humans; Morpholines; Orthopedic Procedures; Patient Safety; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Therapeutic Equivalency; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism

The prevention and treatment of venous thromboembolism (VTE) remains a clinical challenge, primarily owing to drawbacks associated with the use of heparins and vitamin K antagonists (VKAs). These and other factors, including a growing elderly population, mean that VTE presents a continuing burden to patients and physicians. Anticoagulant therapy is a fundamental approach for VTE management. Non-VKA oral anticoagulants, including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban, and the thrombin inhibitor dabigatran, have been studied in phase III trials across a spectrum of thromboembolic disorders. These agents offer simplified care, with similar or improved efficacy and safety outcomes compared with heparins and vitamin K antagonists. There are several factors a physician must consider when prescribing an anticoagulant. An important consideration with all anticoagulant use is bleeding risk, especially in high-risk groups such as the elderly or those with renal impairment or cancer. In orthopaedic patients, other risks include a need for surgical revision or blood transfusion, or wound complications. Therefore, the clinical benefits of an anticoagulant should ideally be balanced with any risks associated with the therapy. Quantitative benefit-risk assessments are lacking, and owing to differences in trial design the non-VKA oral anticoagulants cannot be compared directly. Based on trial and "real-life" data, this review will summarise the clinical data for the non-VKA oral anticoagulants in the prevention and treatment of VTE, focusing on the balance between the benefits and risks of anticoagulation with these drugs, and their potential impact on VTE management.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Heparin; Humans; Male; Orthopedic Procedures; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Thiazoles; Thromboembolism; Treatment Outcome; Venous Thromboembolism; Vitamin K

Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recently authorized so doubts exist about how to use it in daily clinical practice. This document aims to clarify common questions formulated by clinicians regarding the use of this new drug.

Topics: Drug Interactions; Drug Monitoring; Factor Xa Inhibitors; Humans; Recurrence; Rivaroxaban; Venous Thromboembolism

Venous thromboembolism (VTE) causes substantial morbidity and mortality worldwide. The traditional treatment of VTE, with an initial therapy with (low molecular weight) heparin or fondaparinux and a continued treatment with vitamin K antagonists, is effective but has limitations.. The current review summarizes the results of the Phase III trials with the new oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and provides a meta-analysis of these trials in the subgroups of elderly patients (> 75 years) and patients with impaired renal function.. The practical use of direct Xa inhibitors in the treatment of VTE in general and in specific subgroups is discussed. For elderly patients, patients with extremes of body weight, cancer patients or patients with moderate renal impairment, pooled data suggest that the direct oral Xa inhibitors are a reasonable alternative to standard therapy. For other indications, such as treatment of VTE in children, during pregnancy or in the context of heparin-induced thrombocytopenia, further data from clinical trials are needed.

Topics: Administration, Oral; Clinical Trials, Phase III as Topic; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism

The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment of venous thromboembolism, and they are comparable to low-molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty. For other indications, however, such as the prevention of stroke in patients with mechanical heart valves, initial studies have been unfavorable for the newer agents, leaving warfarin the anticoagulant of choice. Further studies are needed before the target-specific anticoagulants can be recommended for patients with cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also persist about difficulties with the laboratory assessment of anticoagulant effect and the lack of a specific reversal agent. For these reasons, we anticipate that the vitamin K antagonists will continue to be important anticoagulants for years to come.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Venous Thromboembolism; Warfarin

Three factor Xa inhibitors have been studied in the treatment of venous thromboembolism, both for acute therapy and as extended therapy to prevent recurrent events. Rivaroxaban, apixaban, and edoxaban have all proven to be effective in Phase III clinical trials for this indication when compared to current standard of therapy with similar or less bleeding. Nevertheless, the agents all offer different pharmacological profiles, which have an impact on patient selection and potential advantages in clinical practice.

Topics: Animals; Blood Coagulation; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism

Four non-vitamin K antagonist oral anticoagulants, apixaban, dabigatran, edoxaban, and rivaroxaban, have been evaluated in phase III clinical trials for the treatment of acute venous thromboembolism, and all except edoxaban have also been studied for extended secondary prophylaxis after venous thromboembolism. Rivaroxaban, and recently also dabigatran, has been approved for this indication, and it is therefore timely to review the characteristics, efficacy, and safety of these drugs with emphasis on patients with venous thromboembolism. This review focuses on the clinical results from the phase III trials, separately for each of the drugs as compared with vitamin K antagonists. We also address the results from meta-analyses that were published recently. Finally, the results in some special groups of interest-renal impairment, elderly patients, and patients with cancer-are reviewed, although they only comprised small minorities of the study populations. All 4 drugs demonstrated noninferiority against vitamin K antagonists in the acute treatment and clear superiority against placebo in the extended treatment (not performed with edoxaban). The risk of bleeding was generally lower with non-vitamin K antagonist oral anticoagulants, and the reduction of risk of intracranial hemorrhage seems to mirror the experience from atrial fibrillation trials. In conclusion, during the past 30 years we have moved from a week of hospitalization and intravenous heparin therapy, via low-molecular-weight heparin injections subcutaneously and early discharge from the hospital, to the possibility of only oral outpatient therapy without coagulation monitoring, yet safe for patients with acute venous thromboembolism.

Topics: Administration, Oral; Animals; Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles; Time Factors; Treatment Outcome; Venous Thromboembolism

A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and safety of direct factor Xa inhibitors (rivaroxaban and apixaban) with enoxaparin for the prevention of venous thromboembolism (VTE) after total knee replacement.. A systematic literature search in Medline, EMBASE, EBSCO, Springer, Ovid and Cochrane library databases was performed to identify RCTs comparing rivaroxaban/apixaban with enoxaparin for the prevention of VTE after total knee replacement. The outcomes including deep vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding were pooled using risk ratios (RRs) with their 95% confidence intervals (95% CIs) as statistic.. A total of 6 RCTs with 13,790 patients were included in this meta-analysis. Overall, the incidence of DVT was significantly decreased with the use of direct Xa inhibitors (both twice daily [b.i.d] and once daily [q.d.] regimes) comparing with the enoxaparin treatment (P<0.01); however, there was no significant influencing difference between direct Xa inhibitors (b.i.d. regime) and enoxaparin on the incidence of PE (P=0.06), while significantly lower rate was found for q.d. regime of direct Xa inhibitors (P=0.02). With respect to major bleeding, the pooled analysis did not demonstrate a significant difference between direct Xa inhibitors (b.i.d. and q.d. regimes) and enoxaparin (30mg and 40mg b.i.d.).. In conclusion, our results confirmed that direct Xa inhibitors (rivaroxaban and apixaban) were more effective for prevention of VTE after total knee replacement as compared with enoxaparin, without increasing major bleeding risk.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Four new oral anticoagulants (NOAC), apixaban, rivaroxaban, edoxaban, and dabigatran, are now available in the USA; however, only apixaban and rivaroxaban are FDA approved for the prevention of venous thromboembolism following orthopedic surgery. Apixaban, rivaroxaban, and edoxaban's anticoagulant activity can be measured using a chromogenic anti-factor Xa assay but there is no widely available means of measuring dabigatran blood levels. None of the NOAC has an antidote. Dabigatran is 80% renally excreted, and patients with atrial fibrillation taking dabigatran for stroke prevention should stop the drug 4-5 days prior to major orthopedic surgery. Apixaban, rivaroxaban, and edoxaban should be held for 48 h preoperatively in this setting.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Orthopedic Procedures; Postoperative Care; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

In the last few years, a new category of anticoagulants have been developed, the non-vitamin K oral anticoagulants (NOACs). The NOACs are of two classes: the direct thrombin inhibitor, namely dabigatran etexilate; and the oral factor Xa inhibitors rivaroxaban, apixaban and edoxaban, which have been proven to be as effective and safe (and sometimes, superior) compared to warfarin in the treatment of both atrial fibrillation (AF) and venous thromboembolism (VTE). One major concern about their use has always been the lack of an effective antidote or reversal strategy. The objective of this editorial is to provide an overview of the characteristics of NOAC antidotes that are in development. Moreover, we review their likely place in the management of NOAC-related bleeding episodes.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

To review current literature for target-specific oral anticoagulants (TSOACs) and provide critical analysis for dosing recommendations in special population groups.. A literature search was conducted in Medline (1996 to April week 2 2015) and Embase (1980 to 2015 week 16) using key terms dabigatran, rivaroxaban, apixaban, edoxaban, kidney diseases, liver diseases, elderly, obesity, and special populations.. Randomized controlled trials in English assessing efficacy and safety of TSOACs in healthy adults and special populations were selected for analysis.. Phase 3 trials for TSOACs predominately excluded patients with severe renal impairment or active liver disease. There were no exclusion criteria based on age, body weight or body mass index. Additional conclusions were made in special populations, including those with renal or liver impairment and obese and elderly patients, based on secondary analyses, pharmacokinetic, and pharmacodynamic studies.. Pharmacokinetic and pharmacodynamic changes associated special populations may alter clinical decision with regard to drug selection and dosing. It is valuable to understand the rationale for labeled dosing recommendations in nonvalvular atrial fibrillation and venous thromboembolism treatment and prevention, particularly in patients that fall into special population groups. Furthermore, the use of TSOACs is likely to increase as clinicians gain experience with these agents and additional TSOACs and indications are approved.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Humans; Kidney Diseases; Liver Diseases; Obesity; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism

Rivaroxaban has proven efficacious in a variety of conditions. In fact, rivaroxaban has been approved for the prevention of venous thromboembolism after elective hip or knee replacement surgery, for the prevention and treatment of deep vein thrombosis and pulmonary embolism, for the prevention of stroke in patients with nonvalvular atrial fibrillation and for the prevention of atherothrombotic events after acute coronary syndrome with elevated cardiac biomarkers. However, clinical development of rivaroxaban is ongoing. Considering published and on-going randomized clinical trials, noninterventional studies and registries, over 275,000 patients are being analyzed. The aim of this review was to update the clinical development of rivaroxaban, including completed and ongoing studies not only randomized clinical trials, but also clinical practice studies.

Topics: Atrial Fibrillation; Factor Xa Inhibitors; Humans; Rivaroxaban; Stroke; Treatment Outcome; Venous Thromboembolism

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Contraindications; Dabigatran; Drug Interactions; Humans; International Normalized Ratio; Male; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thiophenes; Venous Thromboembolism

The risk of venous thromboembolism (VTE) increases with age. New oral anticoagulants (NOACs) have been increasingly studied for VTE prophylaxis in patients with elective postarthroplasty. Although the elderly population accounts for a significant proportion of patients requiring VTE prophylaxis, safety and efficacy of NOACs in this subgroup for VTE prophylaxis has not been well studied. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov (from inception to 12 August 2014). Phase III randomized controlled trials that compared NOACs against low-molecular-weight heparin (LMWH) in the prevention of VTE prophylaxis in patients with elective postarthroplasty were included. We defined our elderly population as adults of at least 75 years and assessed the reported safety and efficacy outcomes with NOACs in this population. Study-specific odds ratios (ORs) were calculated and between-study heterogeneity was assessed using the I statistic. In nine trials involving 29 403 patients, the risk of VTE or VTE-related deaths in elderly patients with elective postarthroplasty was similar with NOACs compared with LMWH (OR 0.62, 95% confidence interval 0.30-1.26; P = 0.18; I = 44%) but bleeding risk was significantly lower (OR 0.71, 95% confidence interval 0.53-0.94; P = 0.02; I = 0%). Analysis of individual NOACs showed superior efficacy but similar safety for apixaban when compared with LMWH. Efficacy and safety profiles of rivaroxaban and dabigatran were similar to LMWH. In elderly patients with elective postarthroplasty, NOACs have similar efficacy but superior safety when compared with enoxaparin for VTE prophylaxis.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dabigatran; Female; Heparin, Low-Molecular-Weight; Humans; Male; Odds Ratio; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Survival Analysis; Treatment Outcome; Venous Thromboembolism

The decision to prescribe anticoagulant therapy must consider the balance between reducing the risk of thromboembolic events and increasing the risk of bleeding. Although assessments of net clinical outcomes with oral anticoagulants are not new, this article presents an evaluation of benefit-risk by considering only events of substantial and comparable clinical relevance (i.e., events with serious long-term sequelae likely to have irreversible consequences, including death). This is based on the concept of the number of patients who need to be treated to elicit one beneficial [number needed to treat (NNT)] or harmful [number needed to harm (NNH)] event. The approach is illustrated using data from phase III trials of rivaroxaban, selected because it has the broadest range of approved indications of the novel oral anticoagulants. For example, in the ATLAS ACS 2 TIMI 51 trial of rivaroxaban plus standard antiplatelet therapy following an acute coronary syndrome event, the current analysis demonstrates that 63 patients need to be treated (over 24 months) to prevent one all-cause mortality event compared with placebo (NNT = 63). Conversely, 500 patients need to be treated to cause one additional intracranial hemorrhage (NNH = 500). The most relevant and clinically meaningful assessment of benefit-risk may therefore be achieved by focusing only on events of greatest concern to patients and physicians, namely those with (potentially) long-lasting, severe consequences. Although there are clear limitations to this type of analysis, rivaroxaban appears to demonstrate a broadly favorable benefit-risk profile across multiple clinical indications.

Topics: Acute Coronary Syndrome; Factor Xa Inhibitors; Humans; Numbers Needed To Treat; Risk Assessment; Rivaroxaban; Stroke; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The treatment of pulmonary embolism is going to be deeply modified by the development of Direct Oral Anticoagulants (DOACs). There are currently three anti-Xa factors (rivaroxaban, apixaban, edoxaban) and one anti-IIa factor (dabigatran) labeled by the FDA and the EMA. All these drugs are direct anticoagulant, orally effective, without the need for adaptation to hemostasis test. As kidney excretion is involved for all of them, they are contra-indicated in patients with severe renal failure (creatinine clearance < 30 mL/min according to Cockcroft & Gault formula). All the anti-Xa factor drugs are metabolized by liver cytochromes and then contra-indicated in case of liver insufficiency. Of note, the four DOACS have been evaluated in non-inferiority trials, including one open-label trial (the EINSTEIN program with the rivaroxaban). Moreover, two of them (rivaroxaban and apixaban) were evaluated in a single drug approach (provided initial increased doses: 15 mg bid during 21 days for rivaroxaban and 10 mg bid during 7 days for apixaban) whereas the two others (edoxaban and dabigatran) were evaluated after at least 5 days of parenteral heparin. They were found to be non-inferior to the conventional treatment, but also seem to be associated with a decreased risk of major bleeding, in a quite young and without significant comorbidities population. The risk/benefit ratio of DOACs in specific subgroups deserves prospective validations.

Topics: Antithrombins; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Thiazoles; Venous Thromboembolism

Pulmonary embolism is a potentially life-threatening condition in which a clot can travel from the deep veins, most commonly in the leg, up to the lungs. Previously, a pulmonary embolism was treated with the anticoagulants heparin and vitamin K antagonists. Recently, however, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTI) and oral factor Xa inhibitors. The new drugs have characteristics that may be favourable over conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or re-dosing and few known drug interactions. To date, no Cochrane review has measured the effectiveness and safety of these drugs in the long-term treatment (minimum duration of three months) of pulmonary embolism.. To assess the effectiveness of oral DTIs and oral factor Xa inhibitors for the long-term treatment of pulmonary embolism.. The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched January 2015) and the Cochrane Register of Studies (last searched January 2015). Clinical trials databases were also searched for details of ongoing or unpublished studies. We searched the reference lists of relevant articles retrieved by electronic searches for additional citations.. We included randomised controlled trials in which patients with a pulmonary embolism confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor for the long-term (minimum duration three months) treatment of pulmonary embolism.. Two review authors (LR, JM) independently extracted the data and assessed the risk of bias in the trials. Any disagreements were resolved by discussion with the third author (PK). We used meta-analyses when we considered heterogeneity low. The two primary outcomes were recurrent venous thromboembolism and pulmonary embolism. Other outcomes included all-cause mortality and major bleeding. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI).. We included five randomised controlled trials with a total of 7897 participants. Two studies tested oral DTIs (dabigatran) and three studies tested oral factor Xa inhibitors (one rivaroxaban, one edoxaban and one apixaban).Analysis showed no difference in the effectiveness of oral DTIs and standard anticoagulation in preventing recurrent pulmonary embolism (OR 1.02, 95% CI 0.50 to 2.04; two studies; 1602 participants; high quality evidence), recurrent venous thromboembolism (OR 0.93, 95% CI 0.52 to 1.66; two studies; 1602 participants; high quality evidence), deep vein thrombosis (DVT) (OR 0.79, 95% CI 0.29 to 2.13; two studies; 1602 participants; high quality evidence) and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; two studies; 1527 participants; high quality evidence).For oral factor Xa inhibitors, when we combined the three included studies together in meta-analyses, there was significant heterogeneity for recurrent pulmonary embolism (OR 1.08, 95% CI 0.46 to 2.56; two studies; 4509 participants; I(2) = 58%; moderate quality evidence). The oral factor Xa inhibitors were no more or less effective in the prevention of recurrent venous thromboembolism (OR 0.85, 95% CI 0.63 to 1.15; three studies; 6295 participants; high quality evidence), DVT (OR 0.72, 95% CI 0.39 to 1.32; two studies; 4509 participants; high quality evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; one study; 4817 participants; moderate quality evidence) or major bleeding (OR 0.97, 95% CI 0.59 to 1.62; two studies; 4507 participants; high quality evidence). None of the studies measured quality of life.. Moderate to high quality evidence suggests that there are no differences between DOACs and standard anticoagulation for the long-term treatment of pulmonary embolism, for the outcomes recurrent pulmonary embolism, recurrent venous thromboembolism, DVT, all-cause mortality and major bleeding.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Dabigatran; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Anticoagulation with low molecular weight heparin and vitamin K antagonists is the current standard of care (SOC) for venous thromboembolism (VTE) treatment and prevention. Although novel oral anti-coagulants (NOACs) have been compared with SOC in this indication, no head-to-head randomised controlled trials (RCTs) have directly compared NOACs. A systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of NOACs for the initial and long-term treatment of VTE.. Electronic databases (accessed July 2014) were systematically searched to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban versus SOC. Eligible patients included adults with an objectively confirmed deep vein thrombosis (DVT), pulmonary embolism (PE) or both. A fixed-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as relative risks (RR) and 95% credible intervals (Crl).. Six Phase III RCTs met criteria for inclusion: apixaban (one RCT; n = 5,395); rivaroxaban (two RCTs; n = 3,423/4,832); dabigatran (two RCTs; n = 2,539/2,568); edoxaban (one RCT; n = 8,240). There were no statistically significant differences between the NOACs with regard to the risk of 'VTE and VTE-related death. Apixaban treatment was associated with the most favourable safety profile of the NOACs, showing a statistically significantly reduced risk of 'major or clinically relevant non-major (CRNM) bleed' compared with rivaroxaban (0.47 [0.36, 0.61]), dabigatran (0.69 [0.51, 0.94]), and edoxaban (0.54 [0.41, 0.69]). Dabigatran was also associated with a significantly lower risk of 'major or CRNM bleed' compared with rivaroxaban (0.68 [0.53, 0.87]) and edoxaban (0.77 [0.60, 0.99]).. Indirect comparisons showed statistically similar reductions in the risk of 'VTE or VTE-related death for all NOACs. In contrast, reductions in 'major or CRNM bleed' for initial/long-term treatment were significantly better with apixaban compared with all other NOACs, and with dabigatran compared with rivaroxaban and edoxaban. Results from the current analysis indicate that the NOACs offer clinical benefit over conventional therapy while highlighting relative differences in their bleeding profile.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Time Factors; Treatment Outcome; Venous Thromboembolism

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode.

Topics: Age Factors; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Dabigatran; Disease Management; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fondaparinux; Humans; Male; Morpholines; Obesity; Polysaccharides; Postthrombotic Syndrome; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Sex Factors; Thiophenes; Thrombophilia; Ultrasonography; Venous Thromboembolism; Venous Thrombosis; Warfarin

Altering doses and regimens of a drug has consequences for the drug's pharmacokinetic and pharmacodynamic profile. Based on a half-life of 5-13 h, it is expected that the Factor Xa inhibitor rivaroxaban would be best suited to a twice-daily rather than a once-daily dose regimen. However, although rivaroxaban is used as a twice-daily regimen for the initial treatment of venous thromboembolism (VTE) and secondary prevention after acute coronary syndromes, the approved dosing is once-daily for prevention of VTE after orthopaedic surgery, long-term secondary prevention of VTE and stroke prevention in patients with non-valvular atrial fibrillation. Rivaroxaban dosing was based on the evaluation of the efficacy and safety of several rivaroxaban doses and regimens in phase II trials. A clear overall advantage of twice-daily dosing compared with once-daily dosing was not documented for indications for which once-daily dosing was subsequently selected. Once-daily dosing was therefore selected for these indications because it is expected to be associated with better compliance than twice-daily dosing, and potentially, with improved outcomes. These studies and data obtained with another Factor Xa inhibitor, edoxaban, in addition to previous experience with low molecular weight heparins, indicate that the clinical impact of once-daily versus twice-daily doses on outcome in terms of efficacy and safety cannot be reliably predicted from pharmacology data, e.g. elimination half-life, obtained during pre-clinical and early phase I clinical studies but rather should be ascertained empirically in phase II and III clinical trials.

Topics: Acute Coronary Syndrome; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Male; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.. We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models.. Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban.. NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

Rivaroxaban (Xarelto(®)), an oral direct factor Xa inhibitor, is approved for the initial treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as the prevention of recurrent DVT and PE. It is administered at a fixed oral dose and does not require routine coagulation monitoring. In the EINSTEIN-DVT and EINSTEIN-PE trials, in over 8,000 patients with DVT and/or PE, a single-drug approach with rivaroxaban was shown to be noninferior to standard therapy consisting of subcutaneous enoxaparin sodium overlapping with and followed by an oral dose-adjusted vitamin K antagonist (enoxaparin-VKA) with regard to the incidence of symptomatic recurrent venous thromboembolism (VTE) after 3, 6 or 12 months of treatment. Rivaroxaban was generally well tolerated in patients with DVT or PE, with no significant between-group differences in clinically relevant bleeding between the rivaroxaban and enoxaparin-VKA groups. Notably, rivaroxaban was associated with a significantly lower rate of major bleeding compared with enoxaparin-VKA when EINSTEIN-DVT and EINSTEIN-PE data were pooled. Pharmacoeconomic analyses indicated that rivaroxaban may be a cost-effective alternative to enoxaparin-VKA for the treatment of DVT or PE and prevention of recurrent VTE. Extended prophylaxis with rivaroxaban reduced the incidence of symptomatic recurrent VTE to a greater extent than placebo in the EINSTEIN-Extension trial, but was associated with a non-significant increase in the risk of clinically relevant bleeding compared with placebo. In conclusion, rivaroxaban is a reasonable alternative to standard therapy for the treatment of DVT and PE, and as extended thromboprophylaxis.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thromboembolism; Venous Thrombosis

During the past four years the phase III trials on stroke prophylaxis in atrial fibrillation and on treatment of venous thromboembolism have been completed for four new oral anticoagulants - dabigatran, apixaban, edoxaban and rivaroxaban. The studies have revealed advantages in terms of a reduced risk of bleeding, most importantly of intracranial bleeding. These anticoagulants also have favourable pharmacokinetics, eliminating the need for routine laboratory monitoring and dose adjustments. There are, however, some differences between the drugs in certain subsets of patients, according to patient characteristics or to indication for treatment. These features are reviewed here. The management of patients in association with invasive procedures or major bleeding is also discussed. Finally, a strategy of how to select patients for warfarin or the new anticoagulants and thereafter possibly also among the latter is outlined.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Morpholines; Patient Selection; Pyrazoles; Pyridines; Pyridones; Risk; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Warfarin

Direct oral anticoagulants (DOACs) specifically target factor IIa or Xa and represent a major step forward in the treatment of acute- and long-term prevention of venous thrombo-embolism (VTE). They are at least as effective and as safe as conventional therapy (heparins and vitamin-K inhibitors) and have practical advantages, such as fixed dosing and no need for laboratory monitoring. These antithrombotic agents introduce a new paradigm for the day-to-day management of VTE. Direct oral anticoagulants should streamline the management of most patients with VTE and will facilitate care in the outpatient setting. Nevertheless, it remains uncertain how to select specific DOACs for particular profiles of patients, and the optimal management of bleeding complications is evolving.

Topics: Acute Disease; Administration, Oral; Antithrombins; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Long-Term Care; Morpholines; Perioperative Care; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

Anticoagulation therapy is one of the most important advances in modern medicine, saving thousands of lives from the complications of atrial fibrillation and mechanical heart valves and preventing recurrent venous thromboembolism. Warfarin and heparins have been the predominant anticoagulants used until the past decade. However, the arrival of newer target-specific anticoagulants has brought us easier and equally effective agents, although no specific antidotes are yet available. Being relatively newer drugs, physicians need to be familiar with the various practical issues that may be encountered with the prescription of these drugs, which are summarised in this review.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Warfarin

The acceptability of warfarin has been limited by mandatory laboratory monitoring. A number of new orally active anticoagulants (NOACs), which can be used as alternatives to warfarin, are now available.. We review the clinical indications and considerations associated with the use of the NOACs.. The NOACs currently approved in Australia are dabigatran, rivaroxaban and apixaban. Indications include thromboprophylaxis in non-valvular atrial fibrillation and following hip and knee replacement surgery. Rivaroxaban is also approved for treatment and secondary prevention of deep venous thrombosis (DVT) and pulmonary embolus (PE). The NOACs differ from warfarin in that they do not require laboratory monitoring. They need to be used cautiously in patients with renal impairment and are contraindicated in patients with renal failure. Bleeding may require blood product replacement aided by haematological advice and specialist investigations. Antidotes to the NOACS are undergoing clinical trials.

Topics: Anticoagulants; Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Dabigatran; Drug Monitoring; Factor Xa Inhibitors; General Practice; Hemorrhage; Humans; Kidney; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.

Topics: Anticoagulants; Clinical Trials, Phase III as Topic; Dabigatran; Hemorrhage; Humans; Outcome Assessment, Health Care; Patient Acuity; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Venous Thromboembolism

Hospitalized medical and surgical patients encompass a group of patients in whom venous thromboembolism (VTE) poses a major concern on morbidity and mortality. Recently, direct oral anticoagulants for the prevention of VTE have been developed to overcome the drawbacks of the food/drug interactions and the need for frequent laboratory monitoring and dose adjustments associated with the use of vitamin K antagonists and the inconvenience of the subcutaneous administration of low-molecular-weight heparins and fondaparinux. The novel oral anticoagulants that have been tested in major clinical trials for VTE prevention in medical and surgical patients are the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, which will be the focus of this review. While the new drugs proved to be highly effective and safe in the prevention of VTE following major orthopedic surgery, they failed to show a favorable benefit-to-risk profile in hospitalized medical patients receiving extended anticoagulation beyond the hospital stay.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Half-Life; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism; Vitamin K

For decades the antithrombotic management of venous thromboembolism (VTE) was limited to parenteral heparin formulations and oral vitamin K antagonists. Even though both classes of anticoagulants are effective, they have several limitations, including a narrow therapeutic window and the need to monitor anticoagulant activity. Direct oral anticoagulants (DOACs) that specifically target factor IIa or Xa have emerged. Recent data suggest that they are at least as effective and as safe as conventional therapy and have practical advantages, such as fixed dose regimen and no need for laboratory monitoring. Hence, they represent a major step forward in the acute treatment and long-term prevention of VTE. In this review, we outline the use of DOACs in the management of VTE and provide an overview of recently published major trials.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism

The new oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, are poised to replace warfarin for treatment of the majority of patients with venous thromboembolism (VTE). With a rapid onset of action and the capacity to be administered in fixed doses without routine coagulation monitoring, NOACs streamline VTE treatment. In phase 3 trials in patients with acute symptomatic VTE, NOACs have been shown to be noninferior to conventional anticoagulant therapy for prevention of recurrence and are associated with less bleeding. Rivaroxaban and dabigatran are already licensed for VTE treatment in the United States, and apixaban and edoxaban are under regulatory consideration for this indication. As the number of approved drugs increases, clinicians will need to choose the right anticoagulant for the right VTE patient. To help with this decision, this review (1) compares the pharmacologic profiles of the NOACs, (2) outlines the unique design features of the phase 3 trials that evaluated the NOACs for VTE treatment, (3) reviews the results of these trials highlighting similarities and differences in the findings, (4) provides perspective about which VTE patients should receive conventional treatment or are candidates for NOACs, and (5) offers suggestions about how to choose among the NOACs.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Therapy; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism

New oral anticoagulants (NOACs) have emerged as an alternative therapy to warfarin in the treatment of arterial and venous thromboembolism and in stroke prevention in patients with non-valvular atrial fibrillation (AF). Three of them, i.e., dabigatran, rivaroxaban, and apixaban, have been approved for clinical use in North America and in a number of European countries. In non-valvular AF, their approval was based on large randomized trials showing that they are non-inferior or even, in some instances, superior to warfarin. Dabigatran is a direct thrombin (factor IIa) inhibitor; rivaroxaban and apixaban are direct factor Xa inhibitors. Before using NOACs, it is recommended to become familiar with their pharmacological characteristics and their metabolism. The absence of specific antidotes is often cited as part of the possible weaknesses of NOACs. Antidotes are perceived to be useful in emergency situations such as life-threatening bleeding or non-elective major surgery. NOACs do not require blood monitoring, and therefore, patient compliance to the treatment is essential. For the present time, there are no specific antidotes available for the three NOACs approved for clinical use. However, phase I or phase II research studies in this area are ongoing. For dabigatran, a specific antidote has been tested in a rat model of anticoagulation, and a study in healthy male volunteers has been recently reported. For rivaroxaban, prothrombin complex concentrates (PCCs) have been found to completely reverse the prolongation of the prothrombin time induced by this NOAC. For apixaban, recombinant factor VII was found in an experimental study using human blood to be superior to activated PCC (aPCC) and PCC. More specific antidotes for rivaroxaban and apixaban are in phases I and II evaluation. The management of patients suffering from a major bleeding or requiring a non-elective major surgery includes non-specific reversal agents and is discussed in the light of a recent position paper and of current literature. Most recommendations are based on expert opinions only as randomized trials using agents for reversal of anticoagulation in case of life-threatening bleeding or of major urgent surgery are not available.

Topics: Animals; Antidotes; Antithrombins; Benzimidazoles; beta-Alanine; Blood Coagulation; Dabigatran; Elective Surgical Procedures; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

The aim was to perform a review of the efficacy and safety of new oral anticoagulants (NOAs) in the management of venous thromboembolism (VTE).. This was a systematic review and meta-analysis. On March 26, 2014, Medline, Embase, and the Cochrane trial register were searched for randomized controlled trials (RCTs) comparing the NOAs dabigatran, rivaroxaban, apixaban, and edoxaban with vitamin K antagonists (VKAs) in VTE treatment and secondary prevention. Two investigators assessed the methodological quality of the RCTs. The main study outcomes (efficacy, safety and net clinical benefit) were expressed as risk ratios (RR) with 95% confidence interval (CI).. Ten RCTs, mostly with low risk of bias, with nearly 38,000 patients, were identified. In six trials of treatment, NOAs were equally effective as VKAs in preventing recurrent symptomatic VTE (RR 0.89, 95% CI 0.75-1.05), but major bleeding occurred less often (1.08% vs. 1.73% for VKAs, RR 0.63, 95% CI 0.51-0.77), leading net clinical benefit to favor NOAs (RR 0.79, 95% CI 0.70-0.90). Fatal bleeding occurred less often with NOAs (0.09% vs. 0.18% for VKAs), a difference that approached statistical significance (RR 0.51, 95% CI 0.26-1.01). In three secondary prevention trials, NOAs reduced VTE recurrence rates to 1.32% (vs. 7.24% with placebo, RR 0.17, 95% CI 0.12-0.24) and fatal pulmonary embolism (PE) (including unexplained deaths) to 0.1% (vs. 0.29% for placebo, RR 0.37, 95% CI 0.10-1.38) at the expense of clinically relevant non-major bleeding (4.3% vs. 1.8% for placebo, RR 2.32, 95% CI 1.65-3.35), but not major bleeding. All-cause mortality rate was reduced to 0.41% with NOAs (vs. 0.86% with placebo, RR 0.38, 95% CI 0.18-0.79). Net clinical benefit favored NOAs (RR 0.21, 95% CI 0.15-0.29), and NNT was 18.. Compared to VKAs, NOAs are not only effective in treating VTE but also safer in terms of bleeding, thereby conferring clinical benefit. Their safety and efficacy was confirmed further in secondary prevention trials.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Thiophenes; Venous Thromboembolism

In the last 4 years, 6 phase 3 trials including a total of 27,023 patients with venous thromboembolism (VTE) compared a direct oral anticoagulant (DOAC) with vitamin K antagonists (VKAs). To aid the clinician in assessing the amount of information, we address frequently raised clinical questions in a review of combined trial results. We included the phase 3 trials that compared dabigatran etexilate, rivaroxaban, apixaban, or edoxaban with VKA therapy in patients with acute symptomatic VTE. Recurrent VTE occurred in 2.0% of DOAC recipients compared with 2.2% in VKA recipients (relative risk [RR] 0.90, 95% confidence interval [CI] 0.77-1.06). Treatment with a DOAC significantly reduced the risk of major bleeding (RR 0.61, 95% CI 0.45-0.83). In parallel, intracranial bleeding, fatal bleeding, and clinically relevant nonmajor bleeding occurred significantly less in DOAC recipients. The efficacy and safety of DOACs were consistent in patients with pulmonary embolism, deep venous thrombosis, a body weight ≥100 kg, moderate renal insufficiency, an age ≥75 years, and cancer. In conclusion, DOACs and VKAs have similar efficacy in the treatment of acute symptomatic VTE, a finding that is consistent in key clinical subgroups. Treatment with a DOAC significantly reduces the risks of major bleeding.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Benzimidazoles; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism; Vitamin K

To systematically examine discontinuation rates with new US Food and Drug Administration-approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation.. Poor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence.. Eighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio [RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators.. Study drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous thromboembolism/pulmonary embolism and prevention of stroke in patients with atrial fibrillation but were worse in acute coronary syndromes as noted in evidence from contemporary RCTs.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Medication Adherence; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

Acute venous thromboembolism (VTE) is a common disease associated to significant morbidity and mortality.. We systematically reviewed and meta-analysed clinical outcomes with direct oral anticoagulants (DOAC: dabigatran, rivaroxaban, apixaban or edoxaban) for treatment of acute VTE. We used MEDLINE and CENTRAL, clinical trials registers, conference proceedings, and websites of regulatory agencies to identify randomised clinical trials of DOAC compared with conventional treatment [parenteral anticoagulant followed by a vitamin K antagonist (VKA)] for acute VTE. Two investigators independently extracted data. Relative risk of recurrent VTE, bleeding events, deaths and a net clinical endpoint (composite of recurrent VTE, major bleeding, and death) were estimated using a random effect meta-analysis (RevMan software).. Six trials including 27,127 patients were selected. The risk of recurrent VTE was similar with the DOAC and standard treatment (relative risk 0.91, 95% confidence interval 0.79 to 1.06). The DOAC reduced the risk of major bleeding in comparison with standard treatment (0.62, 0.45 to 0.85) (absolute risk difference, -0.6%; 95% confidence interval -1.0% to -0.3%), but there was heterogeneity across trials in the relative risk of bleeding. No between treatment differences were found in the relative risk of all-cause mortality (0.98, 0.84 to 1.14). The DOAC and conventional treatment differed on the net clinical endpoint (0.85, 0.75 to 0.97). Subgroup analyses in relevant subgroups (index pulmonary embolism, heparin lead-in, age, gender, renal function, presence of cancer), as well as sensitivity analyses, were consistent with the main analysis.. The DOAC seem as effective as, and probably safer than standard treatment of acute VTE. The relative efficacy and safety of the DOAC was consistent across a wide range of patients.

Topics: Administration, Oral; Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism

Many new oral anticoagulants (NOACs; dabigatran, rivaroxaban, and apixaban) are currently available to treat thromboembolic disease. There are no head-to-head trials comparing these agents. To assess the efficacy and safety of NOACs for prevention of recurrent venous thromboembolism (VTE), we performed a network meta-analysis.. Medline, Embase, and the Cochrane-controlled trial register were searched, without language restriction, to identify trials. Studies were evaluated according to a priori inclusion criteria and appraised using established internal validity criteria. Adjusted indirect comparisons between agents were performed using well-established methods.. Three trials meeting inclusion criteria were identified. Direct comparison between apixaban 2.5 mg twice daily (BID) versus apixaban 5 mg BID showed no difference for any outcome. Clinically relevant non-major bleeding occurred less with both apixaban 2.5 mg BID (OR 0.23, 95% CI 0.08-0.62, P=0.004) and apixaban 5 mg BID [OR 0.31, 95% CI 0.11-0.82, P=0.019] compared to rivaroxaban 20 mg daily. Apixaban 2.5 mg BID showed less clinically relevant non-major bleeding than dabigatran 150 mg BID [OR 0.4, 95% CI 0.16-0.9, P=0.04], but not apixaban 5 mg BID. There were no differences between rivaroxaban 20 mg daily and dabigatran 150 mg BID. No differences in risk for recurrent VTE, major bleeding, or mortality were observed for any comparison between any pair of NOACs.. There were no significant differences in risk for recurrent VTE, major bleeding, or all-cause mortality between the NOACs. However, apixaban 2.5 mg BID was associated with less clinically significant non-major bleeding than either rivaroxaban 20 mg daily or dabigatran 150 mg BID.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Chi-Square Distribution; Dabigatran; Hemorrhage; Humans; Morpholines; Odds Ratio; Pyrazoles; Pyridones; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Warfarin, a vitamin K antagonist, is the most widely used oral anticoagulant in the world. It is cheap and effective, but its use is limited in many patients by unpredictable levels of anticoagulation, which increases the risk of thromboembolic or haemorrhagic complications. It also requires regular blood monitoring and dose adjustment. New classes of drugs, non-vitamin K antagonist oral anticoagulants (NOACs), are now supported as alternatives to warfarin. Three NOACs are licensed: dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, antagonists of factor Xa. NOACs do not require routine blood monitoring or dose adjustment. They have a rapid onset and offset of action and fewer food and drug interactions. Current indications include treatment and prophylaxis of venous thromboembolism and prevention of cardioembolic disease in non-valvular atrial fibrillation. Effective antidotes are lacking and some caution must be used in severe renal impairment, but favourable trial evidence has led to their widespread adoption. Research is ongoing, and an increase in their use and indications is expected in the coming years.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Dabigatran; Drug Administration Schedule; Evidence-Based Medicine; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Venous Thromboembolism; Vitamin K; Warfarin

Target-specific oral anticoagulants (apixaban, rivaroxaban, and dabigatran) are widely available for the treatment of venous thromboembolism (VTE). Although analyses comparing these agents to placebo or warfarin exist, direct comparisons of these agents for extended VTE treatment have not been conducted. Therefore, this network meta-analysis aimed to evaluate the efficacy and tolerability of VKA and target-specific oral anticoagulants for extended VTE treatment using a mixed-treatment comparison, meta-analytic approach.. A comprehensive literature search of EMBASE and MEDLINE was conducted to identify relevant randomized, controlled trials published in English between 1960 and November 2013. Eligible studies investigated the extended use (≥6 months) of oral anticoagulants (apixaban, dabigatran, rivaroxaban, and/or warfarin [conventional or low dose]) and placebo in patients with confirmed VTE. Search terms included extension or extended treatment or therapy, venous thromboembolism (or VTE), deep vein thrombosis (or DVT), pulmonary embolism (or PE), and anticoagulant or anticoagulant agent. Key articles were cross-referenced for additional studies. The efficacy end points evaluated were recurrent VTE or death from any cause, DVT, and nonfatal pulmonary embolism PE. Tolerability end points included major bleeding and nonmajor or clinically relevant bleeding. The data were screened, evaluated, and entered into statistical software to generate direct and indirect comparisons of the various anticoagulants across each study. The data are reported as rate ratios and 95% credible intervals.. Ten trials were analyzed and aggregated, representing data from >14,000 patients. With respect to efficacy end points, no statistically significant between-treatment differences in the composite end point of VTE or death, nonfatal PE, or DVT were found. Major bleeding was significantly greater with warfarin versus apixaban (rate ratio, 4.24; credible interval, 1.28-25.0), and the risk for major bleeding varied somewhat with warfarin and greatly with rivaroxaban. The assessment of nonmajor or clinically relevant bleeding did not identify any meaningful differences between these agents.. The majority of the data represented in this study were derived from noninferiority trials. In the present meta-analysis, efficacy end points in the extended treatment of VTE with apixaban, dabigatran, rivaroxaban, warfarin (conventional and low dose), and placebo were not significantly different. Elevated bleeding risks were identified with rivaroxaban and warfarin; however, the wide credible intervals with rivaroxaban prevent the interpretation of these increased risks.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) comprises both deep vein thrombosis and pulmonary embolism. VTE is a leading cause of morbidity and mortality worldwide and its increasing incidence and prevalence are a major health concern. The primary medical objective during the acute phase of VTE treatment is to prevent thrombus extension and embolization. Extended treatment aims to prevent or minimize long-term complications, such as recurrent VTE, post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension.. Anticoagulant therapy has been the mainstay of treatment for VTE and traditionally involves initial therapy with heparin, overlapping with and followed by a vitamin K antagonist. Although effective, standard heparin/vitamin K antagonist therapy has several limitations that can be overcome by more recently developed target-specific oral anticoagulants (TSOACs). These agents have predictable pharmacokinetics, a rapid onset of action and few drug-drug or drug-food interactions. Furthermore, TSOACs offer convenient anticoagulation without the need for routine coagulation monitoring and dose adjustment.. The efficacy and safety data from phase III clinical trials support the use of TSOACs for VTE treatment, including in special patient populations. Risk-stratification tools and strategies have been developed to assist physicians in managing anticoagulation treatment.. Rivaroxaban is the first TSOAC to gain widespread approval for the treatment of acute deep vein thrombosis and pulmonary embolism and the long-term prevention of recurrent VTE as monotherapy. Dabigatran has also been approved for this indication recently. TSOACs, especially as monotherapy, represent a paradigm shift in clinical practice for the management of patients with VTE.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily dose is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery, the long-term prevention of stroke in patients with non-valvular atrial fibrillation, and the long-term secondary prevention of recurrent VTE. Twice-daily dosing is required in the acute phase of treatment in patients with VTE and in the combination of rivaroxaban with standard single or dual antiplatelet therapy for secondary prevention after acute coronary syndrome events. This article reviews the empirical and clinical rationale supporting the dose regimens of rivaroxaban in each clinical setting.

Topics: Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Hip Joint; Humans; Morpholines; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

Rivaroxaban is a factor Xa inhibitor recently approved for use in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Older adults are at an increased risk for venous thromboembolism (VTE), and rivaroxaban offers an alternative to standard treatment including vitamin K antagonists. This review evaluates the literature supporting this new indication with a focus on the safety and efficacy in older adults as well as those with renal insufficiency and fragility, which the EINSTEIN-PE study defined as those older than 75 years of age, weighing 50 kg or less, or with a creatine clearance (Clcr) of less than 50 mL/min. Three large studies (EINSTEIN-PE, -DVT, -EXT) provide an evaluation of recurrent VTE and bleeding events with the use of rivaroxaban. EINSTEIN-DVT and EINSTEIN-PE showed rivaroxaban to be equivalent to standard treatment in the overall population as well as in older adults and those with renal insufficiency and fragility. Further, EINSTEIN-EXT showed benefit of rivaroxaban over placebo for extended VTE protection (i.e., longer than 6 to 12 months of treatment), both overall and in the subgroups of those older than 75 years of age and with a Clcr of 50 mL/min to < 80 mL/min..

Topics: Aged; Aged, 80 and over; Aging; Factor Xa Inhibitors; Humans; Kidney; Morpholines; Pulmonary Embolism; Recurrence; Renal Insufficiency; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism and atrial fibrillation are among the most common cardiovascular disorders in the United States. For over 50 years, the standard of care has been anticoagulation with vitamin K antagonists. However, the numerous limitations of vitamin K antagonists led to the development of target-specific oral anticoagulants. Dabigatran, rivaroxaban, apixaban, and edoxaban have been shown to be as effective as warfarin in the treatment and prevention of venous thromboembolism and prevention of stroke in nonvalvular atrial fibrillation. This article compares the basic pharmacologic properties of these anticoagulants, reviews the data supporting their use, and discusses practical clinical issues including measurement of the anticoagulation effect, reversal strategies, and management of patients prior to surgery.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Interactions; Humans; Medication Adherence; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) is a major cause of morbidity, mortality, and healthcare expenditure. In the United States, approximately 0.1 % of the population experiences an initial VTE event each year. Anticoagulation therapy is the cornerstone of acute VTE treatment and for prevention of recurrent VTE events. Conventional anticoagulants, including heparin, low-molecular-weight heparins, fondaparinux, and vitamin K antagonists are widely used but have limitations. Newer oral anticoagulant agents, including direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban) have been developed to attempt to overcome some of the limitations of conventional anticoagulant therapy. These new oral agents have been evaluated for safety and efficacy in large, randomized clinical trials in the treatment and secondary prevention of VTE with results that are comparable to conventional therapy. Dabigatran, rivaroxaban, apixaban, and edoxaban are important new treatment options for patients with VTE. In this review, we compare these new agents and their associated clinical trials in VTE treatment.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism

EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Recognize the high risk of postoperative venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. 2. Distinguish the different pharmacological mechanisms of VTE prophylaxis drugs. 3. Delineate the advantages and disadvantages of each VTE prophylaxis drug. 4. Recognize that rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage. Patients undergoing major orthopedic surgery are at high risk for developing postoperative venous thromboembolism (VTE). The authors analyzed the available evidence on the efficacy and safety of dabigatran, apixaban, and rivaroxaban vs low-molecular-weight heparins (LMWHs) as VTE prophylaxis in major orthopedic surgery. Outcomes evaluated included total VTE, deep venous thrombosis (DVT), pulmonary embolism (PE), death, and major bleeding. Rivaroxaban and apixaban are more efficacious than dabigatran and are as safe as dabigatran. Rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Heparin, Low-Molecular-Weight; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Vitamin K antagonists (VKAs) have long been the standard of care for treatment of venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF). Despite their efficacy, their use requires frequent monitoring and is complicated by drug-drug interactions and the need to maintain a narrow therapeutic window. Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have become alternative options to VKAs owing to their predictable and safe pharmacological profiles. The overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding harm, varies according to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in patients with acute coronary syndrome, NOACs are associated with incremental bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are associated with the greatest benefits by reducing both ischaemic events and haemorrhagic complications and might reduce mortality compared with VKAs. The role of NOACs continues to evolve as these drugs are evaluated in different patient populations, including those with renal impairment or with AF and undergoing percutaneous coronary intervention.

Topics: Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Ischemia; Morpholines; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Venous Thromboembolism

To compare key features of the new oral anticoagulants (NOACs)-dabigatran, rivaroxaban, and apixaban-and to address questions that arise when comparing the NOACs.. PubMed was searched for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation (AF) and for the treatment of acute venous thromboembolism (VTE).. All NOACs are at least as effective as warfarin for stroke prevention in patients with nonvalvular AF, and are at least as safe in terms of bleeding risk according to 3 large trials. Meta-analyses of these trials have shown that, compared with warfarin therapy, NOACs reduced total mortality, cardiovascular mortality, and intracranial bleeding, and there was a trend toward less overall bleeding. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring, and few known or defined drug or food interactions. Potential drawbacks of NOACs include a risk of bleeding that might be increased in patients older than 75 years, increased major gastrointestinal bleeding with high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine laboratory test to reliably measure anticoagulant effect, and the lack of an antidote for reversal. No direct comparisons of NOACs have been made in randomized controlled trials, and the choice of NOAC is influenced by individual patient characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity (eg, renal dysfunction).. The NOACs represent important alternatives in the management of patients with AF and VTE, especially for patients who have difficulty accessing regular coagulation monitoring. The companion to this article addresses common "what if" questions that arise in the long-term clinical follow-up and management of patients receiving NOACs.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Antidotes; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Monitoring; Family Practice; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Warfarin

Until recently, only vitamin K antagonists (VKAs) were used for long-term anticoagulation. New oral anticoagulants, with pharmacokinetic and pharmacodynamic characteristics different to VKAs, are now available for some indications. Rivaroxaban (Xarelto®) is an oral Factor Xa inhibitor approved in many countries for long-term treatment of patients with atrial fibrillation or venous thromboembolism. This article is addressed to all professionals involved in the management of treated patients to highlight the characteristics of rivaroxaban and provide practical guidance on management of treated patients.. This article is based on a consensus of specialists involved in the management of anticoagulant treatment, including thrombosis experts, cardiologists, neurologists, emergency medicine specialists, and general practitioners. The authors performed a nonsystematic review of the literature, and expressed guidance statements based on the results of the review as well as personal experience.. Availability of new anticoagulant drugs, including rivaroxaban, is an important step forward to allow easier, more effective, and safer long-term anticoagulation in patients in whom adequate anticoagulation is currently denied due to the limitations of VKAs. However, given their totally new properties, associated risks, and expected broad clinical use, expert professionals and manufacturers must urgently tackle a series of issues.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Consensus; Drug Interactions; Drug Substitution; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Humans; Medication Adherence; Morpholines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Novel oral anticoagulants (OACs), including dabigatran etexilate, rivaroxaban, and apixaban, are available alternative anticoagulant therapy to vitamin K antagonists. The US Food and Drug Administration (FDA) has approved dabigatran, rivaroxaban, and apixaban for the treatment of appropriate patients for specific clinical indications. Therapeutic advantages of prescribing the new OACs are related to their predictable pharmacokinetic and pharmacodynamic properties. Dabigatran, rivaroxaban, and apixaban have all been shown to be noninferior to warfarin treatment for stroke prevention in respective phase 3 clinical trials; dabigatran and apixaban were shown to be superior to warfarin as preventive therapy. Dabigatran, rivaroxaban, and apixaban are all approved agents for stroke prevention in patients with nonvalvular atrial fibrillation in the United States and Europe. Among these agents, rivaroxaban is the only FDA-approved drug for the treatment of venous thromboembolism. This article reviews the major clinical trials that investigated the efficacy and safety of the new OACs and the use of these agents in special clinical situations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Drug Approval; Europe; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Therapeutic Equivalency; Thiophenes; United States; United States Food and Drug Administration; Venous Thromboembolism; Warfarin

Two different regimens of enoxaparin (40 mg once daily or 30 mg bid) have been used as control arms in trials of new oral anticoagulants. The choice of enoxaparin comparator may influence the perceived relative efficacy and safety of the newer agents, and we aimed to identify any significant differences between the two enoxaparin regimens.. We searched MEDLINE, EMBASE, and Cochrane Library for randomized controlled trials that compared enoxaparin to oral anticoagulant (apixaban, dabigatran, rivaroxaban) thromboprophylaxis in elective total knee or hip arthroplasty. Total VTE and bleeding events were pooled using fixed-effects meta-analysis and heterogeneity assessed with the I2 statistic. We conducted adjusted indirect comparisons of bid vs once-daily enoxaparin regimes based on new oral anticoagulants as common comparators.. Fourteen randomized controlled trials in hip and knee replacement surgery met the inclusion criteria. Adjusted indirect comparison showed that bid enoxaparin was significantly more effective in preventing VTE than enoxaparin once daily (relative risk [RR], 0.71; 95% CI, 0.61-0.83; P < .00001). For major and clinically relevant hemorrhage, adjusted indirect comparison showed that enoxaparin bid was nonsignificantly associated with increased risk of bleeding (RR 1.27; 95% CI, 0.97-1.65; P = .08) above that of enoxaparin once daily. Subgroup analysis limited to total knee arthroplasty trials showed similar results.. The use of once-daily enoxaparin regimen as control in clinical trials will lead to more favorable estimates of relative efficacy for the new oral anticoagulants than if enoxaparin 30 mg bid had been chosen as a comparator.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Humans; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

To review novel oral anticoagulant (NOAC) trials in the treatment of venous thromboembolism (VTE) and the possible use of risk-stratification tools to guide their use in practice.. MEDLINE and Cochrane databases were searched to identify relevant journal articles published from January 1982 to February 2013. Additional references were obtained from articles extracted during the database search.. NOACs have been developed to optimize VTE management and overcome the limitations of heparin and vitamin K antagonists (VKA). The AMPLIFY and EINSTEIN trials of apixaban and rivaroxaban, respectively, investigated single-drug management of VTE, whereas the edoxaban Hokusai-VTE trial and dabigatran RE-COVER and RE-COVER II trials investigated the use of NOACs with a heparin lead-in. The AMPLIFY and Hokusai-VTE trials are ongoing but the EINSTEIN and RE-COVER trials have demonstrated that rivaroxaban and dabigatran, respectively, are non-inferior to parenteral anticoagulants and warfarin in the management of VTE. Differences in study design complicate the application of study results to clinical practice. There are multiple validated DVT protocols that effectively and safely treat patients in outpatient settings. The pulmonary embolism (PE) severity index (PESI), simplified PESI (sPESI), and other prognostic tools have been used to risk stratify patients with PE by estimating mortality risk to guide outpatient eligibility.. NOACs provide physicians with new therapeutic options in the management of VTE. While heparin and VKAs compose the current standard treatment for VTE, their use will likely disappear as physicians grow comfortable with the adoption of NOACs. As studies have not clearly defined the efficacy of these agents in certain patient populations, further data in special patient populations and risk stratification through the use of VTE severity scores could potentially be adapted to guide anticoagulant management and outpatient treatment eligibility.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Factor X; Heparin; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Thrombin; Venous Thromboembolism; Vitamin K; Warfarin

Antithrombotic trials in venous thromboembolism treatment and prevention, including those evaluating the new oral anticoagulants, have typically evaluated thromboembolism risk as an efficacy endpoint and bleeding risk as a separate safety endpoint. Findings often occur in opposition (i.e. decreased thromboembolism accompanied by increased bleeding, or vice-versa), leading to variable interpretation of the results, which may ultimately be judged as equivocal. In this paper, we offer an alternative to traditional designs based on the concept of a bivariate primary endpoint that accounts for simultaneous effects on antithrombotic efficacy and harm due to bleeding. We suggest a bivariate endpoint as a general approach to the assessment of 'net clinical benefit' in recently published trials and to the design of future trials. Lastly, we illustrate the bivariate endpoint design using two examples: a recently published superiority trial of rivaroxaban (RECORD1) and an ongoing non-inferiority trial of the duration of anticoagulant therapy in children with venous thrombosis (Kids-DOTT).

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Morpholines; Randomized Controlled Trials as Topic; Research Design; Risk; Rivaroxaban; Thiophenes; Venous Thromboembolism

The management of thromboprophylaxis in patients with pelvic and acetabular fractures remains a highly controversial topic within the trauma community. Despite anticoagulation, venous thromboembolism (VTE) remains the most common cause of surgical morbidity and mortality in this high-risk patient group. Although various thromboprophylactic regimes are employed, evidence relating to the most effective method remains unclear. Controversies surrounding screening, the use of prophylactic inferior vena cava filters (IVCF) and chemothromboprophylaxis in polytraumatised patients, particularly those with pelvic and acetabular fractures, form the basis of considerable debate. With the absence of a well-designed clinical trial and the presence of ongoing controversies within the literature, this review will explore current treatment options available to trauma surgeons and highlight differing scientific opinions, providing an update on the role of screening and current available preventative measures. We cover existing as well as recent advances in chemical thromboprophylactic agents and discuss external mechanical compression devices, the usefulness of serial duplex ultrasonography and the role of extended chemothromboprophylaxis on discharge. The evidence behind prophylactic IVCF is also considered, along with reported complication profiles. We conclude with a proposed protocol for use in major trauma centres, which can form the basis of local policy for the prevention of VTE in trauma patients with pelvic and acetabular fractures.

Topics: Acetabulum; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Coumarins; Dabigatran; Fondaparinux; Fractures, Bone; Heparin; Humans; Mass Screening; Morpholines; Multiple Trauma; Pelvis; Polysaccharides; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Thiophenes; Vena Cava Filters; Venous Thromboembolism

Until recently, warfarin had been one of the only treatment options for long-term anticoagulation of patients with atrial fibrillation, venous thromboembolism, or other medical conditions that require chronic anticoagulation. A main concern when treating patients with anticoagulants is balancing the benefits of preventing a thromboembolic event with the risks of bleeding events. The US Food and Drug Administration recently approved 2 new oral anticoagulants, dabigatran and rivaroxaban, for stroke prevention in patients with atrial fibrillation, and is currently reviewing a drug application for a third new oral anticoagulant, apixaban. These new anticoagulants do not require strict and frequent laboratory monitoring, dosing adjustments, or dietary restrictions, and they incur fewer drug-drug interactions than warfarin. However, these new medications do not have specific reversal agents, may require dosage adjustment based on patient renal function, and lack clinical data regarding their long-term safety and efficacy. The 2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for antithrombotic therapy and prevention of thrombosis include recommendations for dabigatran, rivaroxaban, and apixaban for certain indications. Each of the 3 novel oral anticoagulants has specific pharmacokinetic and pharmacodynamic properties that may make them suitable agents for use in specific patient populations. Knowledge of dosing, drug-drug interactions, monitoring parameters, and clinical considerations for each of these new medications will help clinicians decide for which patients they may be best suited to replace conventional therapy with warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Humans; Morpholines; Postoperative Complications; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) represents a common source of morbidity and mortality among patients with malignant disease. In this specific setting, the treatment of VTE is challenging as cancer patients display a high tendency to develop recurrent VTE, as well as anticoagulant-related bleeding complications. Low-molecular-weight heparins have been demonstrated to be more effective in the long-term prevention of recurrent VTE in cancer patients compared with conventional treatment with vitamin K antagonists. A limitation of this therapeutic approach includes the long-term requirement of daily subcutaneous injections, which may be burdensome to patients. Over the past decade, several novel oral anticoagulants have emerged, which can be administered in fixed doses without the need for monitoring. Clinical trials evaluating these agents for treatment in the general VTE population yielded promising results. This review summarizes the current management of cancer-associated VTE, overviews the trials that investigated the novel anticoagulant drugs for the treatment of acute VTE and discusses the potential of these novel agents for use in cancer patients.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Heparin, Low-Molecular-Weight; Humans; Morpholines; Neoplasms; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Warfarin

New oral anticoagulants, acting either as direct factor-Xa or thrombin inhibitors, have been evaluated for the acute and long-term treatment of venous thromboembolism (VTE). Dabigatran and rivaroxaban are as effective as conventional therapy (heparin/vitamin K antagonists) without safety concerns. Rivaroxaban allows a single-drug regimen even in patients with pulmonary embolism, while dabigatran requires 5-7 days of initial heparin treatment. The results of clinical trials with apixaban and edoxaban will become available in the coming months. Rivaroxaban, apixaban and dabigatran are more effective than placebo for the extended treatment of VTE. Apixaban is effective in both therapeutic and prophylactic doses. Considering both efficacy and bleeding complications, all these agents have a favorable net clinical benefit. Dabigatran is as effective and safe as warfarin for the extended treatment of VTE. It is conceivable that the new oral anticoagulants will become the standard therapy for VTE in the next years.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Humans; Middle Aged; Morpholines; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism; Warfarin

The direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, are new oral anticoagulants that are approved in many countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty. All have a rapid onset of action, a low potential for food and drug interactions and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. These agents offer a convenient alternative to conventional anticoagulant drug regimens, including parenteral low-molecular-weight heparins and fondaparinux, and oral adjusted-dose vitamin K antagonists, for the prevention of venous thromboembolism in this surgical setting. This review summarizes the pharmacology, clinical trial results, bleeding risk and practical use of these new oral anticoagulants in clinical orthopaedic practice. Potential issues to be considered when using these oral anticoagulants include renal impairment, potential drug interactions, neuraxial anaesthesia and management of bleeding.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Heparin, Low-Molecular-Weight; Humans; Morpholines; Postoperative Hemorrhage; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

The risk of venous thrombosis extends for an indeterminate length of time following admission to hospital with a medical or surgical condition. Observational studies in surgery show this risk extends for months and perhaps more than one year, for medical patients the risk extends for at least several weeks. Large bodies of evidence support the heightened risk status of hospitalised surgical and medical patients, and that prophylactic measures significantly reduce the risk of thrombosis. Extending thromboprophylaxis for 4-6 weeks with anticoagulants both old and new has been shown to be efficacious and safe in surgical patients. However in populations of medical patients although prolonged anticoagulant thromboprophylaxis has been shown to be efficacious it also results in more bleeding and the risk benefit is not clear. Hence no therapies are approved for prolonged thromboprophylaxis in medical patients. In this area there have been one phase III study of low molecular weight heparin and two completed phase III studies of NOACs. This article briefly summarises our understanding of the background to preventing venous thromboembolism in hospitalised medical patients and reviews the details of the studies using NOACs.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Enoxaparin; Humans; Morpholines; Postoperative Hemorrhage; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Venous Thromboembolism; Warfarin

The new oral anticoagulants (NOACs) dabigatran etexilate, rivaroxaban, and apixaban have been extensively studied for prevention and treatment of venous thromboembolic disease and for stroke prevention in atrial fibrillation. Elderly patients have the highest incidence of thrombotic complications but also have the highest risk of anticoagulant associated bleeding. In this review we critically examine the balance between risks and benefits of NOACs compared with vitamin K antagonists in elderly patients enrolled in phase 3 randomized controlled trials for the management of venous thrombosis and stroke prevention in atrial fibrillation. Results show that the favourable balance between risks and benefits of NOACs is preserved in the elderly population.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Drug Administration Schedule; Humans; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K; Warfarin

Atrial fibrillation (AF) is a common arrhythmia and the leading cause of stroke, an event with high human and economic burden. Novel oral anticoagulants have been approved in many markets as alternatives to warfarin for stroke prevention in patients with AF - dabigatran etexilate, apixaban and rivaroxaban. Given the high burden of AF, and given that new treatments can more effectively prevent stroke than warfarin, but at higher drug cost, there has been a need for systematic evaluation of the costs and benefits of these new treatments. In this study, we summarize the findings of a systematic literature review on the cost-effectiveness of the new oral anticoagulants. We find that there is substantial heterogeneity between the studies and their numerical findings, despite using a common set of four trials for their clinical inputs. However, there is broad consensus among them that each of the novel oral anticoagulants is cost-effective versus warfarin or aspirin.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Drug Administration Schedule; Humans; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Warfarin

To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism.. Systematic review and network meta-analysis.. Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand.. Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms.. 12 articles met our inclusion criteria, with 11,999 patients evaluated for efficacy and 12,167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available.. All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.

Topics: Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Hemorrhage; Heparin; Humans; Magnetic Resonance Angiography; Morpholines; Pulmonary Artery; Pulmonary Embolism; Rivaroxaban; Thiophenes; Thrombolytic Therapy; Tomography, X-Ray Computed; Venous Thromboembolism

Total knee arthroplasty (TKA) is one of the most common orthopedic procedures in the United States. The number of TKAs is expected to rise significantly over the next 2 decades. One of the most common complications after TKA is venous thromboembolism (VTE), which is potentially fatal. The incidence of VTE is effectively reduced by prophylactic anticoagulants, and clinical guidelines have been developed to improve VTE management. However, current anticoagulants have limitations in terms of efficacy, safety, half-life, ease of administration, and patient adherence. Moreover, these anticoagulants require routine monitoring and dose adjustment, and potential bleeding complications represent an important concern. A new generation of anticoagulants, including recently approved rivaroxaban, is being developed to address the shortcomings of current agents. The efficacy and safety of these newer agents are comparable with those of existing ones. Rivaroxaban is the only new oral agent that is approved for use in TKA and that has demonstrated an efficacy superior to that of enoxaparin in phase 3 trials. To optimize the management of VTE prophylaxis after TKAs, orthopedic surgeons must have a thorough understanding of these new oral agents.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Humans; Morpholines; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs.. The review is based on published phase 3 studies, a literature search in PubMed and the authors' clinical experience.. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment.. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Medication Adherence; Morpholines; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism is a common cause of morbidity and mortality among patients undergoing elective orthopedic surgery. Due to the high incidence of venous thromboembolism in this setting, perioperative anticoagulation is the recommended approach for thromboprophylaxis. Low molecular weight heparin (LMWH), fondaparinux and warfarin are the agents commonly used for thromboprophylaxis. The well-recognized limitations of warfarin and the inconvenience and discomfort associated with the subcutaneous administration of low molecular weight heparin and fondaparinux inspired intense investigation to develop novel oral anticoagulants (NOACs) with more predictable pharmacokinetics, fewer drug interactions and no need for regular laboratory monitoring. Three NOACs have been demonstrated to be effective for thromboprophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in large randomized controlled trials. Here we review the pharmacology of rivaroxaban, dabigatran, and apixaban, summarize the major clinical trials of these agents in thromboprophylaxis after THA and TKA, and discuss the clinical factors to be considered by providers when selecting a NOAC for their patients.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Within the past 5 years, the oral anticoagulants rivaroxaban, apixaban, and dabigatran etexilate have been approved for the prevention of venous thromboembolism in adult patients after elective hip or knee arthroplasty in the European Union and many other countries worldwide. These agents differ from the previously available anticoagulants because they selectively and directly inhibit a single factor in the coagulation cascade-rivaroxaban and apixaban inhibit Factor Xa, and dabigatran inhibits Factor IIa (thrombin)-potentially enhancing the predictability of their anticoagulant effect. Currently, although some guidelines provide recommendations for the use of rivaroxaban, dabigatran etexilate, and apixaban in clinical practice, there are still questions regarding the optimal practical management of patients receiving these agents. This article briefly reviews the practical limitations associated with conventional anticoagulants, discusses potential issues with the practical management of the newer oral anticoagulants, and provides clinical experience from a single institution where rivaroxaban and dabigatran etexilate have been used within their approved indications.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Blood Coagulation Tests; Clinical Trials, Phase III as Topic; Contraindications; Dabigatran; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Hematoma, Epidural, Spinal; Humans; Morpholines; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Hemorrhage; Postoperative Nausea and Vomiting; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Anticoagulants can complicate the approach to the management of patients undergoing operative interventions. We review new anticoagulants that have been introduced recently to the market or that are undergoing investigations for treatment of nonvalvular atrial fibrillation and venous thromboembolism prophylaxis: Dabigatran, rivaroxaban, apixiban, and edoxaban.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Loss, Surgical; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Surgical Procedures, Operative; Thiazoles; Thiophenes; Venous Thromboembolism; Warfarin

Data comparing traditional and novel anticoagulants are reviewed, and the potential use of new oral agents for the prevention and treatment of venous thromboembolism (VTE) is assessed.. Practical challenges in using traditional anticoagulants are well established and have led to the search for new oral agents. Apixaban, rivaroxaban, and dabigatran etexilate are new oral anticoagulants that may offer simpler, more effective, and safer treatment and prevention of VTE, which may increase adherence to such therapy, improve outcomes, and decrease overall health care costs. Their immediate onset of anticoagulant effect, ease of oral administration, and lack of needed regular anticoagulation monitoring are of interest in the medical and pharmacy communities. However, in the treatment and prevention of VTE, more data will be needed to determine their ultimate place in therapy. This review is intended to provide pharmacists with an objective overview of practical considerations that can help them understand the clinical data to facilitate their selection of anticoagulants.. Apixaban, rivaroxaban, and dabigatran etexilate are new oral agents for the prevention and treatment of VTE.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Benzimidazoles; Dabigatran; Drug Monitoring; Evidence-Based Medicine; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Effective prophylaxis and treatment of thromboembolic disorders remain suboptimal in many healthcare systems, partly owing to limitations of traditional anticoagulants. New oral anticoagulants have been developed and among these, rivaroxaban, apixaban and dabigatran etexilate are in the most advanced stage of clinical development.. A literature search using the PubMed and ClinicalTrials.gov databases was performed to identify English-language publications. The search was performed up to 31 December 2011 with the terms rivaroxaban OR Xarelto, apixaban OR Eliquis and dabigatran OR Pradaxa. Ongoing, completed and published phase III randomised controlled trials were selected as the primary source of information for the clinical development programme of each drug.. The new oral agents demonstrate several advantages over traditional anticoagulants, including administration at fixed doses and no requirement for routine coagulation monitoring On the basis of phase III clinical trials, rivaroxaban, apixaban and dabigatran etexilate have been approved in many countries for the prevention of venous thromboembolism after hip and knee replacement surgery. Dabigatran etexilate and rivaroxaban have also been approved for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in Europe and the US. In addition, rivaroxaban has been approved in Europe for the treatment of acute deep vein thrombosis and prevention of recurrent venous thromboembolism. Approval of these agents and postapproval monitoring of their safety and efficacy will have implications for primary care.. Rivaroxaban, apixaban and dabigatran etexilate offer the possibility of simplified prevention and treatment strategies for thromboembolic disorders in the outpatient setting.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

Currently available anticoagulants utilized for venous thromboembolism (VTE) treatment and prevention and stroke prevention in patients with atrial fibrillation (AF) have proven effectiveness but are not optimally utilized because of barriers such as the need for subcutaneous administration and requisite routine laboratory monitoring. Rivaroxaban, a novel oral Xa inhibitor, is an alternative to standard therapies utilized for VTE prevention after elective orthopedic surgery, primary and secondary stroke prevention in nonvalvular AF, VTE treatment after an acute VTE event, and secondary prevention after the acute coronary syndromes (ACS).. This article reviews the pharmacology, efficacy, and tolerability of rivaroxaban for VTE prophylaxis in post-orthopedic surgery and medically ill patients, stroke prevention in nonvalvular AF, adjunctive therapy in patients with ACS, and VTE treatment.. International Pharmaceutical Abstracts and EMBASE were searched for English-only clinical trials and reviews published between 1970 and March 15, 2012. PubMed was searched for articles published between 1970 and June 30, 2012. Additional trials and reviews were identified from the citations of published articles.. Eighty-nine publications were identified: 10 clinical trials and 1 meta-analysis were used to obtain efficacy and tolerability data, and 1 analysis of pooled data from the clinical trials was included; 17 pharmacokinetic, pharmacodynamic, and drug-drug interaction studies were included; and 5 cost-analyses were reviewed. These data showed rivaroxaban to be noninferior to enoxaparin for thromboprophylaxis of VTE after total knee and total hip replacement surgery. It was also shown to be noninferior to vitamin K antagonist therapy for primary and recurrent stroke prevention in nonvalvular AF as well as for the treatment of VTE after an acute deep vein thrombosis or pulmonary embolism. It also showed benefit in lowering the risk for major adverse cardiovascular events after ACS. Differences in major bleeding rates were not statistically significant between rivaroxaban and comparators across the various studies, with the exception of ACS, in which there were higher rates of non-coronary artery bypass graft surgery related bleeding and intracranial hemorrhage.. Based on the findings of the studies reported in this review, rivaroxaban is an effective option for the prevention of VTE after orthopedic surgery, stroke prevention for nonvalvular AF, and treatment of VTE. At this time, rivaroxaban cannot be recommended for secondary risk reduction after ACS because of the increased bleeding risk.

Topics: Administration, Oral; Animals; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Morpholines; Orthopedic Procedures; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Venous Thromboembolism

The direct factor Xa (FXa) inhibitors rivaroxaban, apixaban and edoxaban, and the thrombin inhibitor dabigatran etexilate (dabigatran) have gained approval for use in several indications, most notably for the prevention and treatment of venous thromboembolism (VTE) and for the prevention of stroke in patients with atrial fibrillation. Hepatic impairment can affect the disposition of these anticoagulants considerably not only because of the hepatic metabolism of the direct FXa inhibitors but also because moderate to severely impaired hepatic function will affect coagulation. This review describes the key pharmacological properties of novel oral anticoagulants with special attention to patients with impaired hepatic function. In subjects with moderately impaired liver function (i.e. Child-Pugh classification B), the area under the plasma concentration-time curve (AUC) of rivaroxaban (10 mg single dose) is increased by 2.27-fold, which is paralleled by an increase in FXa inhibition. The AUC of apixaban (5 mg single dose) is increased by 1.09-fold, whereas the AUC of edoxaban (15 mg single dose) is decreased by 4.8 % and the AUC of dabigatran (150 mg single dose) is decreased by 5.6 %. Specific labelling restrictions for rivaroxaban, apixaban and dabigatran regarding impaired hepatic function are based on both the Child-Pugh classification and liver-related exclusion criteria applied in pivotal clinical trials. Rivaroxaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients classified as Child-Pugh B and C. Apixaban can be used with caution in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment or in patients with alanine aminotransferase and aspartate aminotransferase levels >2× upper limit of normal (ULN). Apixaban is not recommended in patients with severe hepatic impairment and is contraindicated in those with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Dabigatran is not recommended in patients with elevated liver enzymes (>2× ULN). Dabigatran is contraindicated in patients with hepatic impairment or liver disease expected to have any impact on survival. Currently, edoxaban is not available in the US or European markets. However, the Japanese label did not restrict use in hepatic dysfunction but advises care in patients with severe hepatic impairment.

Topics: Absorption; Anticoagulants; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Humans; Liver Diseases; Metabolic Clearance Rate; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Thrombin; Tissue Distribution; Venous Thromboembolism

After the introduction of warfarin, long-term oral anticoagulation treatment remained unchanged for more than 50 years. Most recently, with the development and approval of new oral anticoagulants, the treatment of medical conditions that require thrombosis prophylaxis and long-term anticoagulation has become more complex. In the case of venous thromboembolism (VTE) prevention after orthopedic surgery, the new oral agents will be less costly than the parenteral alternative. In other settings (such as atrial fibrillation or treatment of acute VTE), the new agents will offer additional convenience at higher cost, but the degree to which they will reduce clinically important events such as thrombosis or bleeding will be limited, especially for patients on optimally controlled warfarin. As the use of the new oral anticoagulants becomes more widespread, it will be important for all clinicians to have a basic understanding of their pharmacology, advantages, and limitations. Although the need to measure or reverse the effect of these drugs will arise infrequently, clinicians--especially hematologists--will desire evidence-based recommendations about how to manage such scenarios, which will require research studies.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Patients undergoing a total hip or total knee arthroplasty are at high risk of thromboembolism in the postoperative period and after hospital discharge; consequently, clinical guidelines recommended thromboprophylaxis for 10-35 days. Although improved surgical techniques and widespread use of anticoagulants have substantially reduced the incidence of thromboembolic events, venous thromboembolic disease is still a dangerous complication and, in these patients, pulmonary embolism remains the main cause of death. Low molecular weight heparins have long been the mainstay of prevention. However, parenteral administration is inconvenient for many patients, which can sometimes cause poor treatment adherence. In recent years, a new class of oral, fixed-dose anticoagulants, with different mechanisms of action, few interactions and a predictable effect, has been developed. At present, a thrombin inhibitor (dabigatran) and two FXa inhibitors (rivaroxaban and apixaban) are available for prophylaxis in patients after total knee or total hip arthroplasty. In several phase III clinical trials, these drugs have been shown to have equal or superior efficacy and a similar degree of safety to conventional therapy with enoxaparin. These new drugs can significantly improve long-term prevention, particularly in the community setting.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

The risk of recurrent venous thromboembolism is nearly 40% of all patients after 10 years of follow up. The risk is higher in patients with permanent risk factors, who should receive indefinite anticoagulation with acenocoumarol or warfarin, except cancer patients who should receive lower doses of low molecular weight heparin The remaining patients should receive a 3-month course of treatment, after which the need to continue this treatment should be reevaluated. The decision to continue should be individually tailored and balanced against hemorrhagic risk. Determination of D-dimer values at the end of treatment and the presence of residual vein thrombosis or right ventricular dysfunction could be useful to identify patients at low risk of recurrence, who can safely discontinue anticoagulation. The emergence of new oral anticoagulants has opened up a new scenario for secondary prevention in the next few years.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Biomarkers; Dabigatran; Fibrin Fibrinogen Degradation Products; Humans; Morpholines; Prognosis; Risk Factors; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thromboembolism

Because of the characteristics of direct oral anticoagulants (DOA), the lack of an antidote to completely reverse their anticoagulant effects, the absence of standardization in monitoring of their effects, and limited experience of their use, specific recommendations for their management in the perioperative period or in emergencies are required. In elective surgery, in patients with normal renal function and low hemorrhagic/ thrombotic risk, DOA should be withdrawn 2 days before the intervention; when the hemorrhagic/ thrombotic risk is higher, bridge therapy with a low molecular weight hepatin beginning 5 days before the intervention is proposed as an alternative. In emergency surgery, systematic administration of hemostatic drugs as prophylaxis is not recommended. In DOA-related acute hemorrhage, administration of prothrombin complex concentrate, fresh plasma or factor VIIa should be evaluated, and general measures to control bleeding should be implemented.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Loss, Surgical; Dabigatran; Humans; Morpholines; Perioperative Care; Postoperative Hemorrhage; Practice Guidelines as Topic; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Withholding Treatment

Rivaroxaban, an oral, direct factor Xa inhibitor, is a small molecule drug capable of inhibiting not only free factor Xa with high selectivity but also prothrombinase-bound and clot-associated factor Xa in a concentration-dependent manner. Clinical studies have demonstrated predictable anticoagulation and confirmed dose-proportional effects for rivaroxaban in humans with a rapid onset (within 2-4 h) and a half-life of 7-11 h and 11-13 h for young and elderly subjects, respectively. For a 10 mg dose, the oral bioavailability of rivaroxaban is high (80-100%) and is not affected by food intake. These favourable pharmacological properties underpin the use of rivaroxaban in fixed dosing regimens, with no need for dose adjustment or routine coagulation monitoring. Rivaroxaban has a dual mode of excretion with the renal route accounting for one-third of the overall elimination of unchanged active drug. Rivaroxaban is a substrate of CYP3A4 and P-glycoprotein and therefore not recommended for concomitant use with strong inhibitors of both pathways, e.g. most azole antimycotics and protease inhibitors. Rivaroxaban is currently approved for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery. Studies using 10 mg rivaroxaban once daily in this indication demonstrated its suitability for a wide range of patients regardless of age, gender or body weight. Further studies in the treatment of VTE, prevention of cardiovascular events in patients with acute coronary syndrome, prevention of stroke in those with atrial fibrillation and prevention of VTE in hospitalized medically ill patients have been reported or are ongoing.

Topics: Administration, Oral; Adult; Age Factors; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biological Availability; Dose-Response Relationship, Drug; Drug Interactions; Female; Half-Life; Humans; Male; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Rivaroxaban (Xarelto®), an oral oxazolidinone-based anticoagulant, is a potent, selective, direct inhibitor of factor Xa that is used in the prevention of venous thromboembolism (VTE) in adult patients after total hip replacement (THR) or total knee replacement (TKR) surgery. In large, clinical trials, oral rivaroxaban 10 mg once daily was more effective than subcutaneous enoxaparin 40 mg once daily in preventing postoperative VTE in patients undergoing THR or TKR surgery. Rivaroxaban was associated with significantly lower incidences of the primary endpoint, total VTE (composite of deep vein thrombosis, non-fatal pulmonary embolism, or death from any cause) compared with enoxaparin regimens across all studies. For example, in the largest trial in patients undergoing THR, total VTE occurred in 1.1% of rivaroxaban recipients and 3.7% of enoxaparin recipients (absolute risk reduction 2.6% [95% CI 1.5, 3.7]) in the modified intent-to-treat population. Notably, the greater efficacy of rivaroxaban was achieved without a significant increase in the incidence of major bleeding episodes compared with enoxaparin; bleeding events were the most frequently reported adverse events across clinical trials. Pyrexia, vomiting, nausea, and constipation were the most frequently reported of the non-bleeding treatment-emergent adverse events in rivaroxaban recipients and occurred at a similar rate to that with enoxaparin treatment. In addition, preliminary pharmacoeconomic analyses in Canada and the US indicate that rivaroxaban is a cost-saving treatment strategy versus enoxaparin. Although the position of rivaroxaban relative to other therapies remains to be fully determined, it is an effective option for the prophylaxis of VTE following THR and TKR.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) is a major healthcare concern and affects more than 1.6 million individuals each year worldwide. Long-term complications include recurrent VTE, chronic thromboembolic pulmonary hypertension and post-thrombotic syndrome. Rivaroxaban is an oral, direct factor Xa inhibitor that has advantages over traditional VTE therapies, including minimal drug and food interactions and no requirement for routine coagulation monitoring. It is currently approved for VTE prevention in adult patients undergoing elective hip or knee replacement surgery. This review evaluates the potential clinical implications of the multicentre, randomised EINSTEIN studies (EINSTEIN DVT and EINSTEIN EXT), which investigated rivaroxaban for the treatment and prevention of recurrent VTE. In EINSTEIN DVT, rivaroxaban was non-inferior to the standard of care (enoxaparin plus a vitamin K antagonist) for recurrent VTE in patients with acute deep-vein thrombosis (DVT) without pulmonary embolism (PE). In EINSTEIN EXT, extended-duration rivaroxaban had superior efficacy to placebo in patients with confirmed DVT or PE who had received 6-12 months of prior VTE treatment. Rivaroxaban was associated with an acceptable safety profile in both studies. The net clinical benefit (efficacy and safety endpoints combined) of rivaroxaban was significantly greater than its comparators. The EINSTEIN studies are the first demonstration that a single drug--rivaroxaban--can be effective for both the initial treatment of DVT and prevention of recurrent VTE. Moreover, the simple, once-daily oral administration of rivaroxaban could potentially improve adherence to extended-duration VTE treatment compared with the current standard of care in individuals with confirmed DVT or PE.

Topics: Aged; Anticoagulants; Blood Coagulation; Drug Administration Schedule; Evidence-Based Medicine; Female; Humans; Male; Middle Aged; Morpholines; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Topics: Clinical Trials, Phase III as Topic; Factor Xa Inhibitors; Humans; Morpholines; Orthopedic Procedures; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) incurs considerable socioeconomic costs, partly owing to the fact that the treatment and prevention of VTE via effective thromboprophylaxis remains suboptimal in the inpatient and outpatient settings of many healthcare systems. A number of organizations-including the National Quality Forum, The Joint Commission, and the Centers for Medicare and Medicaid Services-have established measures to assess and reduce the healthcare burden of VTE. These improvement strategies focus on increasing the use of thromboprophylaxis, implementing existing guidelines, and improving awareness.. Based on clinical trial results, the oral anti-coagulants rivaroxaban, apixaban, and dabigatran etexilate have been approved in many countries for the prevention of VTE in patients after elective hip or knee replacement surgery. Recently, dabigatran etexilate and rivaroxaban have also been approved in the US for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. In addition, rivaroxaban is currently the only newer anti-coagulant that has been approved in Europe for the treatment of deep vein thrombosis and for the long-term prevention of recurrent VTE. These oral anti-coagulants have several advantages over established anti-coagulants, including no need for routine coagulation monitoring and only minimal food and drug interactions. These characteristics, together with convenient oral administration, may improve adherence and quality of life for patients, which could result in reductions in the rate of VTE.. These three oral agents have several advantages over established anti-coagulants and could, therefore, address the unmet needs of patients, physicians, and healthcare systems, with the potential to reduce the burden of anti-coagulant management and the occurrence of VTE.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Economics, Pharmaceutical; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

The present systematic review was conducted to assess the efficacy and safety of apixaban versus other anticoagulants, for the prevention of venous thromboembolism (VTE) following total hip replacement (THR) and total knee replacement (TKR) surgery. Electronic databases were interrogated to identify relevant randomized controlled trials. A series of direct/indirect comparisons and a network meta-analysis were conducted. Indirect comparisons found that the odds ratio of "all VTE and all-cause death" were significantly higher for dabigatran than for apixaban in patients with THR (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.21) and TKR (OR, 1.72; 95% CI, 1.22-2.42). Rivaroxaban showed similar efficacy to apixaban in patients with THR and TKR (OR, 0.69; 95% CI, 0.38-1.25 and OR, 0.83; 95% CI, 0.57-1.19, respectively). No significant differences were observed in bleeding outcomes between treatments. The novel anticoagulants apixaban, rivaroxaban, and dabigatran demonstrated similar or improved efficacy and similar safety compared with current therapies in this indication.

Topics: Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) is a major public health concern since the incidence of VTE rises substantially with age. Furthermore, the diagnosis can be elusive since patients can present differently, causing delay in diagnosis and initiation of treatment and resulting in major morbidity and mortality. In addition to accuracy and precision in diagnosis, antithrombotic therapies are the cornerstones of VTE management. In traditional paradigm, vitamin K antagonists (warfarin), indirect factor Xa inhibitors, and heparin are the foundation in management of VTE. Warfarin has been the only available oral anticoagulant therapy for several decades. Although warfarin is effective in both treatment and prophylaxis against VTE, there are several limitations. Therefore, the novel anticoagulation therapies, including rivaroxaban, apixaban, and dabigatran etexilate, have apparent advantages over warfarin in terms of clinical efficacy and adverse effects. The objective of this review is to describe the background and clinical implications of these novel anticoagulants.

Topics: Acute Coronary Syndrome; Administration, Oral; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K; Warfarin

Venous thromboembolism (including deep vein thrombosis and pulmonary embolism) and atrial fibrillation are common conditions in Western countries. The mainstay of treatment and prevention for these diseases is fast-acting anticoagulant drugs such as heparins and vitamin K antagonists. The use of these drugs is, however, complex and demanding for both patients and physicians. Recently, new antithrombotic drugs that act directly by inhibiting activated coagulation factors such as factor X or thrombin have been developed and investigated in phase III clinical trials. The aim of this article is to review: (i) the need to develop new drugs; (ii) their efficacy/safety as demonstrated in clinical trials; (iii) the need for laboratory monitoring and (iv) the direction towards the use of these new drugs in the real-life clinical situation.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Dabigatran; Drugs, Investigational; Heparin; Humans; International Normalized Ratio; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

Venous thromboembolism (VTE) and its long-term secondary complications are major health problems associated with high rates of morbidity and mortality and considerable costs for healthcare systems. Many patients receive suboptimal therapy, despite the availability of established and effective agents (including low molecular weight heparins, unfractionated heparin, fondaparinux and vitamin K antagonists) and evidence-based, internationally recognised guidelines. Limited knowledge of guidelines, concerns about bleeding risks and the inconvenience of parenteral administration and routine coagulation monitoring contribute to non-adherence to guidelines. Newer oral anticoagulants such as rivaroxaban, dabigatran etexilate, apixaban and edoxaban, which do not have the limitations of established anticoagulants, have been developed.. Phase III randomised controlled trials for the treatment of acute VTE or for secondary prevention of recurrent VTE were identified in the PubMed and ClinicalTrials.gov databases. The search was limited to phase III studies and performed up to 26 March 2012 with the terms 'rivaroxaban OR Xarelto', 'dabigatran OR Pradaxa', 'apixaban OR Eliquis' and 'edoxaban OR DU-176b OR Lixiana'.. A total of ten phase III studies, four published (three rivaroxaban, one dabigatran), three completed with results presented at recent congresses (dabigatran), and three ongoing (two apixaban, one edoxaban) were identified. Published and completed studies showed that rivaroxaban and dabigatran provided effective and convenient short-term treatment for deep vein thrombosis and VTE, respectively, when compared with standard of care, and showed superiority for long-term prevention of recurrent VTE when compared with placebo. Currently, rivaroxaban is the only newer anticoagulant that has been approved in Europe for the treatment of deep vein thrombosis and prevention of recurrent VTE.. Based on results of completed trials, rivaroxaban and dabigatran both may reduce the incidence of secondary complications of VTE and associated socioeconomic costs. Introduction of these newer anticoagulants is likely to have a substantial impact on clinical practice.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Follow-Up Studies; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism

The oral direct factor Xa inhibitors include rivaroxaban and apixaban that recently have been evaluated comprehensively in multiple randomized clinical trials. Based on the efficacy and safety data from these trials, these novel anticoagulants are disseminating throughout clinical practice for thromboprophylaxis in major lower-extremity joint replacement, acute medical illness, atrial fibrillation, and acute coronary syndromes. The advantages of the xabans over vitamin K antagonists include no requirement for routine anticoagulation monitoring as well as a fast and reliable onset of action. The first perioperative limitation of the xabans is the lack of a routine coagulation test for monitoring their anticoagulant effect in scenarios, such as the timing of surgical procedures, the reversal of xaban-related bleeding, and the conduct of regional anesthesia. A second perioperative limitation is the lack of fully validated clinical reversal agents although prothrombin complex concentrate, recombinant factor VIIa, and factor X concentrate are options for xaban reversal in life-threatening bleeding scenarios. Given their clinical efficacy and advantages, further xabans are in clinical development, with edoxaban already in phase III clinical trials. Although the xabans have ushered in a new paradigm for clinical anticoagulation, further clinical trials are indicated to refine their clinical indications even further, such as anticoagulation for patients with mechanical heart valves.

Topics: Acute Coronary Syndrome; Anesthesia, Conduction; Animals; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Morpholines; Perioperative Care; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

The first study on the treatment of venous thromboembolism (VTE) with dabigatran (RE-COVER) was published in 2009. Three additional phase III trials on acute VTE therapy and extended treatment were recently presented. This article reviews the data and, where applicable, compares them with other novel oral anticoagulants, particularly rivaroxaban, for which all phase III trials have been published.. A twin study to RE-COVER (RE-COVER II) confirmed that dabigatran is not inferior to warfarin regarding efficacy and confers a lower risk for clinically relevant bleeding in the treatment of acute VTE for 6 months. Two studies on the extended treatment of VTE with dabigatran showed that the results for efficacy and safety can be extrapolated to another 16 months (mean) of treatment (RE-MEDY) and that dabigatran reduces the risk of recurrence by 90% compared with placebo (RE-SONATE). In the latter case, there is an increase of the risk for clinically relevant bleeding.. Dabigatran offers an alternative to warfarin for treatment of VTE without a need for coagulation monitoring or dose adjustments. Management of patients with VTE could thereby be simplified. Extended treatment might be considered more often for patients at higher risk of recurrence.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Rivaroxaban; Secondary Prevention; Thiophenes; Treatment Outcome; Venous Thromboembolism; Warfarin

To analyse clinical outcomes with new oral anticoagulants for prophylaxis against venous thromboembolism after total hip or knee replacement.. Systematic review, meta-analysis, and indirect treatment comparisons.. Medline and CENTRAL (up to April 2011), clinical trials registers, conference proceedings, and websites of regulatory agencies.. Randomised controlled trials of rivaroxaban, dabigatran, or apixaban compared with enoxaparin for prophylaxis against venous thromboembolism after total hip or knee replacement. Two investigators independently extracted data. Relative risks of symptomatic venous thromboembolism, clinically relevant bleeding, deaths, and a net clinical endpoint (composite of symptomatic venous thromboembolism, major bleeding, and death) were estimated using a random effect meta-analysis. RevMan and ITC software were used for direct and indirect comparisons, respectively.. 16 trials in 38,747 patients were included. Compared with enoxaparin, the risk of symptomatic venous thromboembolism was lower with rivaroxaban (relative risk 0.48, 95% confidence interval 0.31 to 0.75) and similar with dabigatran (0.71, 0.23 to 2.12) and apixaban (0.82, 0.41 to 1.64). Compared with enoxaparin, the relative risk of clinically relevant bleeding was higher with rivaroxaban (1.25, 1.05 to 1.49), similar with dabigatran (1.12, 0.94 to 1.35), and lower with apixaban (0.82, 0.69 to 0.98). The treatments did not differ on the net clinical endpoint in direct or indirect comparisons.. A higher efficacy of new anticoagulants was generally associated with a higher bleeding tendency. The new anticoagulants did not differ significantly for efficacy and safety.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Emergency department (ED) clinicians are not typically involved in the long-term management of patients' anticoagulation therapy, but they are responsible for decision making for emergency conditions requiring anticoagulation, such as acute venous thromboembolism (VTE). In addition, emergency physicians are often faced with patients who present first to the ED with conditions that may prompt long-term anticoagulation upon hospital discharge, such as atrial fibrillation (AF), or who have acute or potential bleeding complications from anticoagulation.. In this review, clinical trials of new oral anticoagulants evaluated for treatment of VTE and stroke prophylaxis in AF, as well as practical management aspects, will be discussed. In addition, clinical trials evaluating the adjunctive use of the new oral anticoagulants with antiplatelet therapy in patients who have experienced acute coronary syndrome will be explored.. Both dabigatran etexilate and rivaroxaban have successfully completed phase III trials for acute VTE treatment and are currently approved for the reduction of risk of stroke and systemic embolism in patients with nonvalvular AF. In a recently completed phase III trial, apixaban also demonstrated promising efficacy and safety in that indication. Rivaroxaban represents the only new anticoagulant to date to have shown promising phase III results as an adjunct to antiplatelet therapy after acute coronary syndrome.. Knowledge of the appropriate clinical use and safety concerns of the new anticoagulants is imperative as they become more frequently prescribed, and their potential uses in the ED setting represent an important aspect of continuing education for emergency physicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Emergency Service, Hospital; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

To evaluate potential drug-drug interactions with rivaroxaban in patients undergoing total hip replacement (THR) and total knee replacement (TKR) surgeries.. PubMed; January 2009-April 2012 abstract databases of major congresses for hematology and cardiovascular medicine.. Searches were performed using the key words rivaroxaban and drug interaction. Studies were included if they evaluated interactions with drugs that are commonly used in patients undergoing THR or TKR, based on our clinical experience.. A Phase 1 study found that coadministration of rivaroxaban and the nonsteroidal antiinflammatory drug (NSAID) naproxen significantly increased bleeding time. However, in a retrospective analysis of 4 large trials evaluating rivaroxaban in patients undergoing THR or TKR, the difference between major and clinically relevant nonmajor bleeding was not significantly different between NSAID users and nonusers. In addition, proton pump inhibitors, which are frequently coadministered with NSAIDs to prevent gastrointestinal toxicity, have not been demonstrated to cause any appreciable changes in rivaroxaban pharmacokinetics or pharmacodynamics. A Phase 2 study that evaluated several doses and administration intervals of rivaroxaban in combination with aspirin or both aspirin and clopidogrel in patients with acute coronary syndrome found that clinically significant bleeding events occurred in patients receiving rivaroxaban 10 mg daily (the dose approved for the orthopedic indication). However, this risk was not great enough to end the trial early.. Phase 1 drug-drug interaction studies in healthy humans provided little insight into the pharmacodynamic drug interactions between rivaroxaban and NSAIDs or antiplatelet agents. A pooled analysis of the RECORD (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials and data from other large trials provides clinical evidence that these agents can be coadministered with rivaroxaban, as long as proper monitoring is instituted.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Interactions; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

The past decade has witnessed important advances in the diagnosis and treatment of venous thromboembolism with excellent opportunities to apply evidence-based medicine for many of the steps in the management of the disease. This review discusses the clinical prediction rules that should be used to reduce utilization of imaging diagnosis for deep vein thrombosis or pulmonary embolism and the risk stratification for thrombolytic therapy or outpatient management of pulmonary embolism. The treatment options have increased and include low-molecular-weight heparin (LMWH), intravenous or subcutaneous unfractionated heparin - the latter either monitored or not monitored, fondaparinux and rivaroxaban for the initial phase. Thereafter, vitamin K antagonists (VKAs), LMWH, oral factor Xa or thrombin inhibitors are or will soon become available. The VKAs have been subjected to many randomised trial addressing the initiation, intensity, monitoring and self-management. Extended anticoagulation and the selection for that is finally reviewed.

Topics: Anticoagulants; Antithrombins; Clinical Trials as Topic; Diagnostic Imaging; Disease Management; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Morpholines; Radiography; Risk; Rivaroxaban; Thiophenes; Thrombin; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

New oral anticoagulant (NOAC) regimens [dabigatran 150 mg (D150) and 220 mg (D220), rivaroxaban 10 mg (R20), and apixaban 2.5 mg bid (A5)] were effective and safe compared to enoxaparin for the prevention of venous thromboembolism (VTE) following elective total knee (TKR) or hip replacement (THR) surgery. First a cluster analysis was used to identify homogeneous studies for the trial programs of each NOAC. Second, only studies reporting VTE and VTE-related death, major bleeding, and mortality were included. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each NOAC regimen versus the comparator. Third, these data were used for the indirect comparison between NOACs. Cluster analysis identified duration of treatment (10 ± 5 and 34 ± 5 days) as the only homogeneous parameter across all NOAC programs (p>0.05) except for A5 and VTE over 10 ± 5 days (analysis not performed). The results of the calculated OR and 95% CI of the four NOAC regimens over 10 ± 5 and 34 ± 5 days showed inferiority of D150 and D220 compared to R10 for VTE (p<0.01, p<0.001). Comparisons of major bleeding and mortality were not different for all indirect comparisons. Despite the lack of standard definitions for VTE and bleeding outcomes, cluster analysis seems to be an appropriate tool to identify homogeneity across trial programs and to perform an indirect comparison for NOACs for prevention of VTE following TKR and THR surgery.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Endpoint Determination; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

A number of novel oral anticoagulants that directly target factor Xa or thrombin have been developed in recent years. Rivaroxaban and apixaban (direct factor Xa inhibitors) and dabigatran etexilate (a direct thrombin inhibitor) have shown considerable promise in large-scale, randomised clinical studies for the management of thromboembolic disorders, and have been approved for clinical use in specific indications. Rivaroxaban is licensed for the prevention of venous thromboembolism in patients undergoing elective hip or knee replacement surgery, the treatment of deep-vein thrombosis and prevention of recurrent venous thromboembolism, and for stroke prevention in patients with non-valvular atrial fibrillation. Based on the clinical trial data for rivaroxaban, feedback on its use in clinical practice and the authors' experience with the use of rivaroxaban, practical guidance for the use of rivaroxaban in special patient populations and specific clinical situations is provided. Although most recommendations are in line with the European summary of product characteristics for the approved indications, additional and, in several areas, different recommendations are given based on review of the literature and the authors' clinical experience.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Blood Loss, Surgical; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Female; Humans; Male; Morpholines; Practice Guidelines as Topic; Pregnancy; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) represents one of the most preventable complications that occur during hospitalization, and measurement of hospital-associated VTE is becoming a key component in hospital quality measures. Guidelines for the prevention of deep vein thrombosis and pulmonary embolism have been published by several organizations to guide quality of care; however, some of the guidelines are divergent in their recommendations. This disagreement among guidelines is most pronounced in patients undergoing major orthopedic surgery. The advent of newer anticoagulants, which are now approved or in late-phase development, have already had an effect on the guidelines and may also affect quality measures in the future. In this article, we review the burden of VTE in patients undergoing major orthopedic surgery, highlight the differences in the guidelines, and examine the new anticoagulants as they are related to VTE prophylaxis in this patient group.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Evidence-Based Medicine; Humans; Morpholines; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Societies, Medical; Thiazoles; Thiophenes; Venous Thromboembolism

Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison.. We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic surgery. We used random effects meta-analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and all-cause mortality), and haemorrhagic adverse events (major and clinically relevant non-major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control.. Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12), and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards increased haemorrhage RR 1.14 (95% CI 0.80-1.64).. Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

A number of new oral anticoagulant drugs that selectively and directly inhibit factor Xa (FXa) appear as promising alternatives to the existing anticoagulant agents. These compounds present a convenient route of administration with predictable pharmacokinetics and pharmacodynamics that allow fixed dosing regimens without requiring coagulation monitoring. Rivaroxaban is the first of this new class of drugs that was approved for the prevention of venous thromboembolism (VTE) after elective total hip replacement or total knee replacement surgery in the EU, Canada and several other countries. Clinical trials with rivaroxaban in patients with acute VTE and in patients with atrial fibrillation have been recently completed. Numerous other compounds are under different developing stages (apixaban, edoxaban, otamixaban, LY517717, PRT-054021, YM150).. This review provides an overview of the two oral anti-FXa drugs at the most advanced stage of development (rivaroxaban and apixaban) and briefly describes and comments on the results of the most important studies.. Undoubtedly, these new drugs will offer several advantages over the previous compounds, but a number of issues still require some attention during the phase of translation from clinical trials into daily clinical practice.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Drugs, Investigational; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Venous Thromboembolism

Rivaroxaban is a novel Xa inhibitor with an encouraging anti-thrombosis effect. The aim of this study is to assess whether rivaroxaban is superior to enoxaparin in venous thromboembolism prevention after knee- or hip-joint replacement.. We searched for reports of randomized controlled trials on rivaroxaban versus enoxaparin in venous thromboembolism prophylaxis after knee- or hip-joint replacement in the Cochrane library, Embase, Pubmed, the Ovid database, and Chinese databases including VIP, CNKI, and CBM. Correlated data was extracted and analyzed.. Eight studies involving 15246 patients were included, and all were randomized controlled studies. The methodological quality of six of the trials was generally moderate, while that of the remaining two was considered high quality. 10mg rivaroxaban daily is more effective than 40 mg/30 mg enoxaparin daily after the joint replacement in respect of the incidence of venous thromboembolism (P < 0.0001, RR = 0.38; P = 0.05, RR = 0.77, respectively). No significant difference between 10mg rivaroxaban daily and 40 mg/30 mg enoxaparin daily were found in major postoperative bleeding (P = 0.45, RR = 1.31;P = 0.34, RR = 1.61, respectively). With respect to other outcomes, rivaroxaban is not inferior to enoxaparin, while extended therapy with rivaroxaban (>30 d) is more effective than short-term therapy (<15 d) in relation to the incidence of venous thromboembolism (1.36% versus 10.13%).. Rivaroxaban is superior to enoxaparin in venous thromboembolism prophylaxis after hip- or knee-joint replacement. Extended therapy--longer than 30 d--is recommended.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Humans; Male; Middle Aged; Morpholines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism; Young Adult

The marketing of new anticoagulant drugs has led us to review the development of rivaroxaban and apixaban (oral anti-Xa drugs) and dabigatran (an oral thrombin inhibitor). The results are different in terms of efficacy and tolerance. Each molecule has its own field of application but it is not at all certain that each will find its place. Though the results are favourable for these orally active drugs in the orthopaedic setting, it is clear that only cardiological applications will give a final green light for these products. The future will be fascinating in this regard.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Biological Availability; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Postoperative Complications; Prothrombin; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thrombosis and pulmonary embolism rarely occur in children but are associated with significant morbidity and mortality. Venous thromboembolism (VTE) mostly affects children with severe underlying conditions and multiple risk factors. Newborns and adolescents are at the highest risk. Standard and low molecular weight heparins and vitamin K antagonists are routinely used for the prevention and treatment of VTE. The new anticoagulants, both parenteral such as argatroban, bivalirudin and fondaparinux and oral such as dabigatran and rivaroxaban, have favourable pharmacological properties, all are approved for clinical use in adults and are currently being investigated in children. Argatroban is the only new anticoagulant licensed for use in children so far. The role of these new anticoagulants as alternative anticoagulants for children remains to be defined. This review focuses on the characteristics of VTE in children and reviews current knowledge on the use of the new thrombin and factor Xa inhibitors in this population.

Topics: Adolescent; Anticoagulants; Arginine; Benzimidazoles; beta-Alanine; Child; Child, Preschool; Dabigatran; Drug Approval; Factor Xa Inhibitors; Fondaparinux; Hirudins; Humans; Infant; Infant, Newborn; Morpholines; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Risk Factors; Rivaroxaban; Sulfonamides; Thiophenes; Thrombin; Venous Thromboembolism

Thromboprophylaxis in orthopedic surgery remains a controversial issue despite recent changes to NICE guidelines, particularly with the addition of oral factor Xa inhibitors. The healthcare burden of venous thromboembolism is substantial and needs frequent academic and clinical appraisal.. The authors review the available relevant literature on the use of rivaroxaban in orthopedic surgery, identified using an EMBASE (1980 - 2010) and Ovid MEDLINE (1950 - 2010) search of published articles up to August 2010. This includes clinical studies, case reports and experimental studies where applicable. Search terms include: 'rivaroxaban', 'safety', 'efficacy', 'bleeding', 'toxicity', 'tolerability' and 'complication'.. Rivaroxaban is a safe and effective choice of thromboprophylactic agent following lower limb arthroplasty surgery. More research is required to expand the application of this novel agent to other areas of orthopedic surgery.

Topics: Anticoagulants; Clinical Trials, Phase III as Topic; Humans; Lower Extremity; Morpholines; Orthopedics; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Anticoagulation for the long-term treatment and prevention of thrombo-embolic diseases as well as for stroke prevention in atrial fibrillation (AF) has been accomplished by vitamin K antagonists for the last half century. Although effective under optimal conditions, the imminent risk of a recurrent event vs. the risk of bleeding due to the narrow therapeutic window, numerous food- and drug interactions, and the need for regular monitoring complicate the long-term use of these drugs and render treatment with these agents complicated. As a result, novel anticoagulants which selectively block key factors in the coagulation cascade are being developed. The efficacy and safety of the direct thrombin inhibitor dabigatran etexilate, as well as of the selective factor Xa inhibitors rivaroxaban and apixaban, have been demonstrated in Phase III trials for stroke prevention in AF and the treatment and secondary prophylaxis of venous thrombo-embolism. This review summarizes the results from recently published pivotal clinical trials and discusses the opportunities as well as uncertainties in the clinical applications of these novel agents.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Drug Approval; Factor X; Humans; Morpholines; Off-Label Use; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

Thromboembolic conditions present a considerable challenge to healthcare services because they are associated with substantial morbidity and mortality. The mainstays of prevention and treatment are anticoagulants and antiplatelet agents. Established anticoagulants have drawbacks that make their use difficult to manage and sustain. This has stimulated the search for new oral anticoagulants that are more convenient and yet still effective. This paper describes the development and future potential of rivaroxaban (Xarelto; Bayer Schering Pharma AG, Berlin, Germany)-the first oral, direct Factor Xa inhibitor to be approved for clinical use in the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery.

Topics: Adult; Animals; Clinical Trials as Topic; Drug Design; Drug Discovery; Fibrinolytic Agents; Humans; Models, Biological; Models, Molecular; Molecular Targeted Therapy; Morpholines; Rivaroxaban; Thiophenes; Validation Studies as Topic; Venous Thromboembolism

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Topics: Aged; Anticoagulants; Antithrombins; Arthroscopy; Bariatric Surgery; Benzimidazoles; Blood Coagulation Disorders, Inherited; Dabigatran; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Kidney; Knee; Laparoscopy; Morpholines; Neoplasms; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism

In total hip or total knee arthroplasty, hypercoagulability typically begins on the operating table and a hypercoagulable state persists for up to 3 months after surgery. For that reason, it is critical to begin anticoagulation as soon as possible after wound closure and to continue it beyond the standard time of hospital discharge: current guidelines recommend up to 35 days following total hip arthroplasty and at least 10 days following total knee arthroplasty. Currently, low molecular weight heparin is commonly used for in-hospital prophylaxis, while for post-discharge use, warfarin is the drug most frequently prescribed in the United States. While both are efficacious, both have challenges associated with administration and, in the case of warfarin, a narrow therapeutic window, both food and drug interactions, routine blood monitoring, and an unpredictable dose response. New oral anticoagulants are being developed that will be easier to administer, have minimal or no drug interactions, and do not require coagulation monitoring. These drugs, which include dabigatran, apixaban, and rivaroxaban, should encourage improved compliance with guideline recommendations for optimal duration of thromboprophylaxis and lead to a reduced incidence of venous thrombolic events.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Morpholines; Outpatients; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Time Factors; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) following joint replacement surgery represents an economic as well as a clinical burden; however, the risk of thromboembolic events is greatly reduced by appropriate anticoagulation. Rivaroxaban, a Factor Xa inhibitor currently in phase III development, was compared with the low molecular weight heparin enoxaparin in 4 clinical trials, collectively called the RECORD program (REgulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism). In a pooled analysis of data from the RECORD trials, rivaroxaban was superior to enoxaparin regimens in reducing the composite end point of symptomatic venous thromboembolism and all-cause mortality in patients following elective primary total hip or total knee arthroplasty (THA or TKA), with a comparable incidence of major bleeding events. In cost-effectiveness analyses, compared with enoxaparin, rivaroxaban showed the potential to reduce costs associated with the prophylaxis and treatment of thromboembolic events in a post-orthopedic surgery/arthroplasty population.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; United States; Venous Thromboembolism

Deep vein thrombosis and pulmonary embolism-the components of venous thromboembolism (VTE)-are significant causes of morbidity and mortality and are a major burden on US healthcare systems. Current VTE prevention strategies are often suboptimal after total hip or total knee arthroplasty, possibly due to drawbacks of the established anticoagulants, resulting in residual VTE and associated (or related) costs of care. New anticoagulant agents under development may address some of the limitations of current options and possibly increase adherence to guidelines for thromboprophylaxis. This article will review the characteristics of the new oral anticoagulants, which may potentially translate into cost savings for the healthcare system.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Cost Savings; Dabigatran; Health Care Costs; Humans; Medication Adherence; Morpholines; Rivaroxaban; Thiophenes; United States; Venous Thromboembolism; Vitamin K

For years, prevention and treatment of thromboembolic events have been restricted to the use of heparins and vitamin K antagonists. These treatments, in spite of their unquestioned efficacy, present numerous limits (hemorrhagic risk, need for regular laboratory controls). These limits call for the development of new antithrombotic drugs. This review briefly reports on three new molecules, in very advanced phases of clinical research: dabigatran (Pradaxa®), rivaroxaban (Xarelto®) and apixaban. These molecules represent new oral anticoagulants, which directly inhibit a coagulation factor (thrombin for dabigatran, factor Xa for rivaroxaban and apixaban) and do not need regular anticoagulant monitoring or dose adjustment. The approval is still restricted in France to the prophylaxis of venous thromboembolism in orthopaedics. Dabigratran will be soon available in the prevention of stroke in atrial fibrillation. With the forthcoming phase III studies to prevent and treat venous thromboembolism, anticoagulant therapy management will be most probably improved in the coming years.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Drug Approval; Drug Monitoring; Factor Xa Inhibitors; Fibrinolytic Agents; Forecasting; France; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombin; Thromboembolism; Thrombophilia; Venous Thromboembolism

Newer therapeutic options available in the prevention of postoperative thromboembolism, currently focused on fondaparinux, rivaroxaban and dabigatran warrant an overall therapeutic assessment. The constitutive comparisons with enoxaparin are based on a combined outcome measure solely driven by the incidence of "asymptomatic deep vein thrombosis". Its validity as a clinically relevant endpoint is missing if antithrombotics of different classes are compared. This is because they target different phases of thrombogenesis i. e. ahead and beyond the asymptomatic stage of thrombosis. Additional concerns refer to the dosing-regimens and their practical administration: Fondaparinux, rivaroxaban and dabigatran are dosed to achieve maximum effects very close to their limits of tolerance whereas wide dosing spectra for the low molecular weight herparin (LMWH)'s indicate the potential for dose adaptation and increase. The other disadvantage to the control-heparin originates in the timing for the 1st administration which doesn't fit in with the "just-in-time" principle. So the enoxaparin-regimen is lacking in benchmark-quality - with the consequence that the meaning of the Phase III-trials does'nt go beyond a mere technical demarcation from the marketed variant of the product as defined by the stipulations in the package insert. As to tolerance the selective anticoagulants exhibit an increased risk of major and other clinically relevant bleeding, exceeding that of enoxaparin by 30% (P<0.001). The outcome of the meta-analyses on fondaparinux, rivaroxaban and dabigatran is supported by product-specific calculations and assessments of the European Medicine Equivalence Agency (EMEA). Rivaroxaban and dabigatran show significant age-dependent renal accumulation. Because the dose-finding studies were restricted to patients over 60 year old the regimens definitely established are not applicable to younger patients. The reason for the limited therapeutic index of the selective anticoagulants originates in their monovalent activity as such not adequately matching the complexity of thrombogenesis and early thrombus extension. Their class-specific limitations are compensated through more intensive dosage-regimens which result in accentuated bleeding complications. Connotatively the hypothesis emerged that antiXa- and IIa-effects interact synergistically which translates into enhanced efficacy and tolerance. Experimental studies on hirudin with pentasaccharide and hirudin with "lo

Topics: Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation; Dabigatran; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

The number of total hip and knee arthroplasties is increasing, with a consequent rise in the number of patients at risk of venous thromboembolism. Each such event is associated with the risk of morbidity and mortality, plus substantial healthcare costs. Consequently, the American College of Chest Physicians guidelines recommend low-molecular-weight heparins, fondaparinux or vitamin K antagonists (usually warfarin) after total hip and knee arthroplasty. However, such agents are also associated with healthcare costs for administration and monitoring. New oral anticoagulants in development may reduce post-arthroplasty symptomatic thromboembolic events and produce potential savings for the healthcare system. This brief article outlines such potential savings with rivaroxaban based on the results of the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) program.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost Savings; Health Care Costs; Humans; Morpholines; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Humans; Morpholines; Orthopedic Procedures; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism

Rivaroxaban (Bayer AG, Leverkusen, Germany) is a highly selective direct inhibitor of factor Xa. It has completed Phase III clinical trials evaluating its efficacy and safety against enoxaparin in the prophylaxis against venous thromboembolism (VTE) in orthopedic patients following primary total hip and total knee arthroplasty. Rivaroxaban has been extensively studied worldwide in 12,729 patients in the Regulation of Coagulation in Major Orthopedic Surgery Reducing the Risk of DVT and PE (RECORD) program. Pivotal clinical trials have demonstrated the superior efficacy in reducing total VTE in comparison with both the North American and European regimens of enoxaparin. Safety of the drug was found to be excellent, with no demonstrable cardiovascular or hepatic effects and no statistically significant increase in major bleeding. A pooled analysis of data collected on the patients from the four RECORD trials revealed rivaroxaban to be the first antithrombotic agent to demonstrate superiority over another antithrombotic (enoxaparin) in reducing symptomatic VTE and all-cause mortality. While there was a significant difference in the composite safety endpoint of major and clinically relevant nonmajor bleeding in the pooled analysis with the use of rivaroxaban compared with enoxaparin, there was no significant difference in major bleeding or in any other bleeding.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials as Topic; Evidence-Based Medicine; Fibrinolytic Agents; Hemorrhage; Humans; Morpholines; Risk Assessment; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Goal of this article is to select three molecules from all the candidates currently under clincial development and to present and comapre their characteristics. Dabigatran is a direct thrombin (FIIa) inhibitor, whereas Rivaroxaban and Apixaban are direct factor Xa (FXa) inhibitors. All three represent small molecules thatreversibly, rapidly and directly bind to their target, the active center of the respective activated coagulation factor. Phase III data have been published for venous thromboembolism prophylaxis for each of these three drugs. Interestingly, VTE prophylaxis is initiated postoperatively with these products. Rivaroxaban currently holds the only accepted indication in Switzerland. For the indications VTE, atrial fibrillation and acute coronary syndrome promising phase III data have been or are in the process of being published. Monitoring is not necessary for any of these three new anticoagulants.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Biological Availability; Clinical Trials, Phase III as Topic; Dabigatran; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Factor Xa Inhibitors; General Practice; Humans; Metabolic Clearance Rate; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Outpatient use of anticoagulants to prevent venous thromboembolism after total hip or knee arthroplasty may be hampered either by requirements for parenteral administration or high variability and frequent monitoring of anticoagulant activity. Trials of the new oral direct factor Xa inhibitors rivaroxaban and apixaban and the direct thrombin inhibitor dabigatran indicate that they can be administered in fixed doses without monitoring and that they generally have efficacy at least equivalent to enoxaparin, although with potential minor differences in the balance of efficacy vs risk for bleeding. This article reviews the results and pharmacokinetic properties that may influence their use in clinical practice.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement; Benzimidazoles; beta-Alanine; Clinical Trials, Phase III as Topic; Dabigatran; Enoxaparin; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism (VTE) is a major public health issue, with a high incidence in hospitalised patients. Furthermore, many VTE events are preventable with appropriate thromboprophylaxis. Medical thromboprophylaxis usually comprises heparins, while warfarin has been the mainstay of long term anticoagulation for many years. Both drugs are limited by their narrow therapeutic index and the need for regular monitoring. The introduction of low molecular weight heparins and fondaparinux has overcome some of these shortfalls but their use remains restricted by requisite parenteral administration. There is a clear need for new anticoagulants with predictable pharmacokinetics and anticoagulant effect. To this end, 2 new agents; dabigatran and rivaroxaban, have recently been licensed for use in orthopaedic thromboprophylaxis. This review discusses the limitations of traditional anticoagulants, and summarises the development and clinical studies pertaining to the use of 3 new targeted anticoagulants: idraparinux, rivaroxaban and dabigatran in VTE, in addition to the limitations of these novel agents.

Topics: Animals; Anticoagulants; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Drugs, Investigational; Humans; Morpholines; Oligosaccharides; Pyridines; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

As an alternative to the inconvenient and labor intensive traditional anticoagulants, Factor Xa inhibitors may offer new options for the prevention and treatment of acute coronary syndromes (ACS) and venous thromboembolism (VTE). Fondaparinux, an indirect FXa inhibitor, has equivalent efficacy but decreased bleeding risk. It has been recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) as the preferred anticoagulant in ACS patients with higher bleeding risk managed with a noninvasive strategy. Based on the composite results of several clinical trials, fondaparinux is also recommended for VTE prevention in the setting of major orthopedic surgery. Rivaroxaban, a direct FXa inhibitor, appears to have at least equal efficacy and safety to established anticoagulants in the prevention of VTE. With advantages such as oral administration and a wide therapeutic window, it may provide a useful alternative to current anticoagulants. Ongoing studies are exploring its use in treatment of VTE and ACS, as well as prevention of stroke among patients with atrial fibrillation. In this review, we examine the key recent studies on efficacy and safety of FXa inhibitors in ACS and VTE management.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Fondaparinux; Humans; Morpholines; Polysaccharides; Rivaroxaban; Thiophenes; Venous Thromboembolism

The search for an oral anticoagulant with acceptable efficacy and safety in the treatment and prevention of venous and arterial thromboembolism, but with practical advantages over warfarin, has been a focus of drug development for many years. Three oral agents, dabigatran, rivaroxaban, and apixaban, are nearing approval in the US. Their use in practice will be guided by the clinical trials available, as well as their pharmacokinetic and pharmacodynamic properties. Practitioners need to be fully aware of these characteristics in order to use these agents appropriately in clinical practice. This review compares the results of the phase 3 trials investigating these agents in the prevention of venous thromboembolism in patients undergoing orthopedic surgery, examines the reporting of bleeding complications in the trials, and highlights various practical considerations regarding their use in clinical practice.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Clinical Trials, Phase III as Topic; Dabigatran; Drugs, Investigational; Evidence-Based Medicine; Humans; Morpholines; Orthopedic Procedures; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

To indirectly compare rivaroxaban and dabigatran for prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA, TKA) based on their pivotal efficacy/safety trials embracing a total of 20618 patients.. Pooled risk differences (RD) for rivaroxaban vs enoxaparin and dabigatran vs enoxaparin obtained from separate meta-analyses of two sets of trials were used to indirectly estimate RDs for rivaroxaban vs dabigatran.. Primary efficacy (any VTE+all-cause mortality) and safety (major bleeding) outcomes in enoxaparin arms largely differed across similarly designed rivaroxaban and dabigatran trials (differences in venography adjudication and bleeding events definitions). However, incidence of symptomatic VTE and incidence of major/non-major clinically relevant bleeding (including surgical site) were consistent in this respect. RDs (as percentages) for symptomatic VTE were: rivaroxaban-enoxaparin=-0.4% (95% confidence interval [CI], -0.9 to 0.05); dabigatran-enoxaparin=-0.09% (95% CI, -1.0 to 0.8); rivaroxaban-dabigatran=-0.3% (95% CI, -1.3 to 0.7; P=0.275). RDs for major/clinically relevant bleeding were rivaroxaban-enoxaparin=0.99% (95%CI, 0.29 to 1.69); dabigatran-enoxaparin=0.02% (95% CI, -1.0 to 1.0); rivaroxaban-dabigatran=0.97 (95% CI, -0.43 to 2.37; P=0.085). Mortality rates (all-cause, VTE-related, bleeding-related) were very low not indicating differences between any two of the three treatments.. Methodological differences disable indirect comparisons of rivaroxaban vs dabigatran that would be based on major efficacy/safety outcomes of their pivotal trials. The two drugs do not seem to differ regarding incidence of symptomatic VTE. Risk of a relevant bleeding is higher with rivaroxaban than with enoxaparin and the same tendency exists also vs dabigatran. Direct rivaroxaban vs dabigatran comparisons in this setting are needed.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Dabigatran; Enoxaparin; Hemorrhage; Humans; Morpholines; Postoperative Care; Pyridines; Randomized Controlled Trials as Topic; Rivaroxaban; Safety; Survival Analysis; Thiophenes; Venous Thromboembolism

Venous thromboembolism is the most frequent preventable cause of death in hospitalized patients. Currently available anticoagulants have limitations that restrict their widespread use, particularly in long-term indications. Vitamin K antagonists require frequent monitoring and dose adjustment, and have a narrow therapeutic window with the risk of bleeding. The low-molecular-weight heparins have more predictable pharmacokinetics and pharmacodynamics, and coagulation monitoring is not required. However, their subcutaneous administration limits their suitability for long-term use. Consequently, many patients fail to receive effective preventive therapy. Rivaroxaban, apixaban, and dabigatran are new anticoagulants in late-stage clinical development that inhibit a single, specific coagulation factor, unlike the Vitamin K antagonists and low-molecular-weight heparins. Studies suggest that they provide effective, predictable anticoagulation with a low bleeding risk and will potentially offer an improved clinical profile and wider safety margin compared with currently available therapies.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Blood Coagulation; Dabigatran; Drug Evaluation; Factor Xa; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombin; Venous Thromboembolism

To review the pharmacology, pharmacokinetics, and clinical efficacy/safety profile of rivaroxaban to inform health-care professionals of this new agent for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery.. A literature search was performed in PubMed/MEDLINE (1966-March 2010), International Pharmaceutical Abstracts (1970-March 2010), and EMBASE (1990-March 2010), limited to publications in English, using the search terms BAY 59-7939, rivaroxaban, factor Xa inhibitor, hip replacement, and/or knee replacement to identify literature sources. References from retrieved articles were evaluated to identify relevant literature. Unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidance, and advisory committee briefing packets.. All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of rivaroxaban for the prevention of VTE in patients undergoing major orthopedic surgery were included, with preference for clinical data.. Rivaroxaban use was significantly more effective for thromboprophylaxis in patients undergoing total knee replacement (TKR) or total hip replacement (THR), compared to enoxaparin for the composite incidence of deep vein thrombosis, nonfatal pulmonary embolism, all-cause mortality, and the rate of major VTE; bleeding events occurred at statistically similar rates. In Phase 3 studies, rivaroxaban 10 mg was administered orally 6-8 hours post-surgery and post-hemostasis. Thereafter, administration was once daily for 35 days in THR and 10-14 days in TKR.. Rivaroxaban has demonstrated comparable safety and superior efficacy to the commonly used low-molecular-weight heparin, enoxaparin. Ongoing and future clinical trials will allow clinicians to further assess the efficacy, safety, and pharmacoeconomics of rivaroxaban.

Topics: Animals; Clinical Trials, Phase III as Topic; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

Acutely ill medical patients are at moderate to high risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Medical conditions associated with a high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, rheumatological and infectious diseases. Pre-disposing risk factors in medical patients include a history of VTE, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility and obesity. Hence active cancer and a history of cancer are both strongly related to VTE in medical (non-surgical) patients. Heparins, both unfractionated (UFH) and low molecular weight (LMWH) and fondaparinux have been shown to be effective agents in prevention of VTE in this setting. However, it has not yet been possible to demonstrate a significant effect on mortality rates in this population. In medical patients, unfractionated heparin has a higher rate of bleeding complications than low molecular weight heparin. Thromboprophylaxis has been shown to be effective in medical patients with cancer and may have an effect on cancer outcomes. Thromboprophylaxis in patients receiving chemotherapy remains controversial and requires further investigation. There is no evidence for the use of aspirin, warfarin or mechanical methods. We recommend either low molecular weight heparin or fondaparinux as safe and effective agents in the thromboprophylaxis of medical patients.

Topics: Anticoagulants; Aspirin; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Neoplasms; Polysaccharides; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

Warfarin is commonly used in a number of clinical settings. Given the difficulties in managing patients taking warfarin, several questions are usually raised by clinicians in relation to its use.. This article addresses some of the clinical questions related to warfarin use.. Routine genetic testing before warfarin initiation is not currently recommended. None of the new oral anticoagulants is marketed in Australia for long term therapy as warfarin substitutes. Strategies to prevent thrombosis associated with air travel are discussed and measures to minimise the risk of bleeding are highlighted.

Topics: Anticoagulants; Aspirin; Benzimidazoles; Dabigatran; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; International Normalized Ratio; Morpholines; Pharmacogenetics; Pyridines; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Venous Thromboembolism

This study aimed to evaluate the cost-effectiveness of prophylaxis with rivaroxaban vs. enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR) from the perspective of the Canadian healthcare system. A model was developed that included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with one-year cycles). Transition probabilities were derived from phase III clinical trials comparing rivaroxaban with enoxaparin and published literature. Costs were derived from the Ontario Case Costing Initiative and publicly available sources. Utilities were derived from published literature. The model reported VTE event rates, quality-adjusted life expectancy and direct medical costs over a five-year horizon. Costs are reported in 2007 Canadian Dollars (C$). When rivaroxaban and enoxaparin are compared in patients undergoing THR, rivaroxaban dominates enoxaparin. That is, rivaroxaban is associated with improved health outcomes as measured by increased quality-adjusted life years (QALYs; 0.0006) and fewer symptomatic VTE events (0.0061), and also with lower cost (savings of C$300) per patient. Similarly, rivaroxaban dominates enoxaparin in patients undergoing TKR, achieving a gain of 0.0018 QALYs, a reduction of 0.0192 symptomatic venous thromboembolic events and savings of C$129 per patient. Rivaroxaban is a cost-effective alternative to enoxaparin for VTE prophylaxis in patients undergoing THR and TKR. Over a five-year horizon, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more quality-of-life benefit at a lower cost.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Canada; Cost-Benefit Analysis; Enoxaparin; Follow-Up Studies; Humans; Morpholines; Postoperative Complications; Quality of Life; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Venous Thromboembolism

Rivaroxaban is a newly developed oral medicine that direct inhibits factor Xa for the prevention and treatment of thromboembolic disorders. The objective of this study was to compare the efficacy and safety of rivaroxaban versus enoxaparin, a medicine routinely used for thromboprophylaxis after total hip or knee arthroplasty.. We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, and Embase. The primary efficacy outcome for our meta-analysis was total venous thromboembolism (VTE) and all-cause mortality. The primary safety outcome was bleeding events, which were categorized as major, clinically relevant non-major, or minor events.. Eight RCTs, involving 15,586 patients, were included in our meta-analysis. Compared to enoxaparin, thromboprophylaxis with rivaroxaban was associated with significantly fewer VTE and all-cause mortality [9,244 patients, risk ratio (RR) 0.56, 95% confidence interval (CI) 0.39-0.80] cases and a similar incidence of bleeding cases (major bleeding events: 13,384 patients, RR 1.65, 95% CI 0.93-2.93; clinically relevant non-major bleeding events: 13,384 patients, RR 1.21, 95% CI 0.98-1.50; total bleeding events, 13,384 patients, RR 1.10, 95% CI 0.97-1.24). The total hip or knee arthroplasty subgroup analysis revealed consistent efficacy and safety findings.. Rivaroxaban was more effective than the recommended dose of enoxaparin and had a similar safety profile for thromboprophylaxis after hip and knee arthroplasty.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Double-Blind Method; Enoxaparin; Hemorrhage; Humans; Incidence; Morpholines; Multicenter Studies as Topic; Odds Ratio; Primary Prevention; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

The traditional agents used for thromboprophylaxis are effective and safe but have limitations particularly related to ease of administration. Newer agents targeting single coagulation factors such as the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban and apixaban have demonstrated efficacy and safety for thromboembolism prophylaxis in the orthopedic population and have the additional benefit of oral administration and predictable pharmacokinetics. Pharmacology of the new anticoagulants and published data on the use of these agents in total knee and hip replacement patients will be reviewed in this article.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Heparin and low molecular weight heparins have limitations in their efficacy and safety for the prevention and treatment of venous thromboembolism (VTE). New synthetic antithrombotic drugs, designed with the intention of improving the therapeutic window for prophylaxis and treatment, are in various stages of development. Synthetic pentasaccharides include fondaparinux and its long-acting analogue idraparinux. Dabigatran is a direct thrombin inhibitor that has undergone clinical trials for VTE prophylaxis and treatment. Direct factor Xa inhibitors include rivaroxiban, which has shown promising results for VTE prophylaxis and is being studied for VTE treatment, as well as apixaban and betrixaban, which are at earlier stages of clinical validation. These newer agents may represent viable options for prophylaxis and therapy as further clinical studies are performed.

Topics: Anticoagulants; Benzamides; Benzimidazoles; beta-Alanine; Dabigatran; Fondaparinux; Humans; Morpholines; Oligosaccharides; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside.

Topics: Anticoagulants; Antithrombin III; Clinical Trials as Topic; Humans; Morpholines; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

The treatment of choice for acute venous thromboembolism is anticoagulant therapy with fast-acting drugs (unfractionated or low-molecular-weight heparin or fondaparinux) aimed at preventing thrombus extension, followed by extended prophylaxis with vitamin K antagonists aimed at preventing recurrence. Experience accumulated over the years has demonstrated that strict laboratory monitoring is required for unfractionated heparin and vitamin K antagonists, making use of these drugs problematic for patients and physicians and prompting researchers to develop new anticoagulants equally effective but without the requirement for laboratory monitoring. The results of clinical trials to date, albeit limited, suggest that these new drugs will probably keep their promise. However, the definitive answer will come subsequent to these clinical trials, when clinicians will start to use these drugs to treat patients in the real world. It is likely that some sort of laboratory monitoring will be required at least for selected categories of patients. Accordingly, clinical laboratories should still be prepared to monitor patients, although the numbers may hopefully decrease sharply in the next decade or so.

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; International Normalized Ratio; Monitoring, Physiologic; Morpholines; Polysaccharides; Prothrombin Time; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Venous thromboembolism is an important complication for patients undergoing surgery. Thromboprophylaxis reduces thromboembolic events.. In this review we discuss the evidence supporting the use of newer agents for thromboprophylaxis, rivaroxaban and dabigatran etexilate. We will also discuss current thromboprophylaxis options for patients undergoing bariatric surgery, including dose and duration of pharmacological prophylaxis and mechanical methods. The most recent The American College of Chest Physicians and American Academy of Orthopedic Surgeons guidelines are also reviewed.. Novel agents may modify our approach to thromboprophylaxis; although these agents offer reduced rates of venographic deep vein thrombosis, their impact on patient important outcomes (clinical deep vein thrombosis, pulmonary embolism and death) requires additional study.

Topics: Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Premedication; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Two selective, orally available anticoagulant agents, although with different targets in the coagulation cascade, have recently been approved in many countries on the indication of prophylaxis against venous thromboembolism (VTE) after major joint arthroplasty. This review discusses mainly the antifactor Xa drug, rivaroxaban, with a focus on the orthopedic trials. Pharmacokinetic characteristics and other clinical development programs with rivaroxaban are briefly reviewed. Although the aim of this article is not to review the direct thrombin inhibitor, dabigatran etexilate, some comparisons are made. For clinical results, these are obviously indirect and conclusions must be drawn with caution until head-to-head comparisons are performed. Whether the introduction of rivaroxaban is a change of paradigm will ultimately be decided in the eyes and mind of the beholder.

Topics: Anticoagulants; Humans; Morpholines; Orthopedic Procedures; Premedication; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Rivaroxaban (Xarelto), an oral oxazolidinone-based anticoagulant, is a potent, selective direct inhibitor of factor Xa that is used in the prevention of venous thromboembolism (VTE) in adult patients after total hip replacement (THR) or total knee replacement (TKR) surgery. In four large, clinical trials, oral rivaroxaban was more effective than subcutaneous enoxaparin in preventing postoperative VTE in patients undergoing THR or TKR surgery. Notably, the superior efficacy of rivaroxaban was achieved with a low but not significant increase in the incidence of major bleeding episodes. In addition, preliminary pharmacoeconomic analyses in several countries indicate that rivaroxaban is a cost-effective treatment strategy versus enoxaparin. Although the position of rivaroxaban relative to other therapies remains to be fully determined, it is an effective emerging option for the prevention of VTE following THR and TKR.

Topics: Animals; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials as Topic; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

For more than 50 years, heparin and vitamin K antagonists (VKAs) have been the anticoagulant drugs used to prevent and treat thrombosis. Low molecular weight heparins (LMWHs) are more recent and have been available for approximately 20 years. Patients with cancer are members of a unique patient population because of their high risk for thrombosis and the risk of anticoagulant-related bleeding. With the currently available antithrombotic agents, patients with cancer still have unmet needs in terms of the prevention and treatment of thrombosis. Although long-term LMWH is the treatment of choice for patients with cancer who have acute, symptomatic venous thromboembolism (VTE), some patients still experience recurrent VTE. More effective antithrombotic agents are needed for such patients. Convenient (ie, oral and with no laboratory monitoring), effective, and safe agents are needed to prevent thrombosis in patients taking chemotherapy and antiangiogenic drugs and in patients with central vein catheters. There are a number of new antithrombotic agents that have been studied in recent years and will soon be available for certain diseases. They target either activated factor X (ie, factor Xa) or activated thrombin, and some of them have potential therapeutic value in patients with cancer. In this article, the clinical research model used for the development of a new antithrombotic agent is discussed along with the results of recent trials that evaluate these new agents in high-risk populations.

Topics: Administration, Oral; Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Factor Xa; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Male; Morpholines; Neoplasms; Prognosis; Pyrazoles; Pyridones; Rivaroxaban; Severity of Illness Index; Survival Analysis; Thiophenes; Treatment Outcome; Venous Thromboembolism

Anticoagulants such as low molecular weight heparins (LMWH; e.g. enoxaparin) and black triangle downfondaparinux are cost-effective measures for reducing the likelihood of venous thromboembolism (VTE) in patients undergoing surgery.1 black triangle downDabigatran etexilate (Pradaxa-Boehringer Ingelheim)2 and black triangle downrivaroxaban (Xarelto - Bayer) are fixed-dose oral anticoagulants licensed in the European Union (EU) for the prevention of VTE in adults who have undergone or are undergoing elective replacement of the hip or knee joints.2,3 Here, we consider their place for these indications.

Topics: Adult; Anticoagulants; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Humans; Morpholines; Pyridines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rivaroxaban for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from four randomised controlled trials (RCTs) comparing rivaroxaban with enoxaparin [RECORD (Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous thrombosis and pulmonary embolism) 1-4] and three comparing dabigatran with enoxaparin [RE-NOVATE (the prevention of venous thromboembolism after total hip replacement trial), RE-MODEL (the prevention of venous thromboembolism after total knee replacement trial) and RE-MOBILIZE (the prevention of venous thromboembolism after total knee arthroplasty trial)]. The evidence from the four RECORD trials indicates that rivaroxaban had superior efficacy over enoxaparin after total hip replacement (THR) and total knee replacement (TKR). For the composite primary outcome of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and death from all causes the relative risk reductions were 70-79% in THR and 31-49% in TKR. Rivaroxaban also had superior efficacy over enoxaparin for the secondary outcome major VTE. Rivaroxaban was not inferior to enoxaparin on the safety outcome of major bleeding. After the correction of some errors found by the ERG, the manufacturer's economic model represented a reasonable model of patients receiving prophylaxis for THR or TKR. In the base-case analyses rivaroxaban dominated both enoxaparin and dabigatran. The incremental costs saved and quality-adjusted life-years (QALYs) gained were small (below 200 pounds and 0.005, respectively, per person). Analyses were conducted sampling from the distributions observed from the RCTs. When all parameters were sampled rivaroxaban dominated enoxaparin in all scenarios except for two, in which enoxaparin produced more QALYs than rivaroxaban and had an incremental cost per QALY gained of 5000 pounds and 8000 pounds respectively. Rivaroxaban dominated dabigatran when RECORD 1 and RECORD 2, individually or pooled, were compared with RE-NOVATE and when all four rivaroxaban RCTs pooled were compared with all three dabigatran RCTs. Dabigatran dominated rivaroxaban compa

Topics: Adult; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Humans; Morpholines; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

The mechanism of action, pharmacodynamics, pharmacokinetics, efficacy in clinical trials, interactions, adverse effects and toxicity, and place in therapy of rivaroxaban are reviewed.. Rivaroxaban, the first oral, direct factor Xa (FXa) inhibitor to reach Phase III trials, inhibits thrombin generation by both the intrinsic and the tissue factor pathways. It has shown predictable, reversible inhibition of FXa activity, and it may have the ability to inhibit clot-bound FXa. Rivaroxaban is being evaluated for prevention of venous thrombosis in patients undergoing hip or knee arthroplasty, treatment of venous thrombosis, long-term use for secondary prevention of venous thrombosis, and prevention of stroke in atrial fibrillation. To date, only short-term trials have been reported, but rivaroxaban's safety and efficacy appear to be at least equivalent to those of traditional anticoagulants. The results of four studies of primary prevention of venous thrombosis in patients undergoing orthopedic surgery suggest that rivaroxaban 10 mg daily is a promising alternative to low-molecular-weight heparins. Rivaroxaban appears to have a low potential for drug-drug or drug-food interactions. It offers the advantages of a fixed oral dose, rapid onset of action, and predictable and consistent anticoagulation effect, precluding the need for routine monitoring of anticoagulation.. Rivaroxaban is a promising alternative to traditional anticoagulants for the prevention and treatment of venous thromboembolism and for stroke prevention in atrial fibrillation; it offers once-daily oral administration without the need for routine monitoring.

Topics: Aging; Antithrombin III; Clinical Trials as Topic; Drug Interactions; Fibrinolytic Agents; Hepatic Insufficiency; Humans; Morpholines; Obesity; Prothrombin Time; Renal Insufficiency; Rivaroxaban; Thiophenes; Venous Thromboembolism

Important clinical data with a significant impact on the clinical management of venous thromboembolism (VTE) were presented at The International Society of Thrombosis and Haemostasis (ISTH) meeting, held in Geneva, Switzerland in July of 2007. In addition, 2 new guidelines for the management of patients with acute coronary syndromes (ACS) were published in 2007, and will have a significant impact on daily practice. Finally, the approval of new practice-changing, paradigm-shifting oral anticoagulants is on the horizon. This article will review the top 4 advances in antithrombotic care and discuss their impact on the clinical management of VTE.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Advances in antithrombotic therapy began when traditional anticoagulant agents such as heparin and the vitamin K antagonists like Coumadin became commercially available in the 1940s and 1950s. Inherent limitations of these compounds, including the need for monitoring and multiple food and drug interactions (with coumadin), spurred the development of newer parenteral compounds like low molecular weight heparin, the pentasaccharide fondaparinux, and direct thrombin inhibitors such as hirudin, argatroban and bivalirudin with advantages over traditional compounds. Despite the failure of the first oral anticoagulant in 50 years--the direct thrombin inhibitor ximelagatran--due to issues with liver toxicity, new oral agents such as the Factor Xa inhibitors rivaroxaban, apixaban, YM-150, and DU-176b and oral direct thrombin inhibitors such as dabigatran are in advanced stages of development, with dabigatran and rivaroxaban now approved for use outside of the United States for thromboprophylaxis in the setting of orthopedic surgery. These and other novel agents have the potential to greatly expand our armamentarium to treat thromboembolic disease, with more targeted approaches to specific procoagulant complexes, a predictable anticoagulant response that does not require monitoring, and use in both acute and long-term treatment settings.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Drug Discovery; Factor Xa Inhibitors; Humans; Morpholines; Oligosaccharides; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism

To summarise and critically evaluate the evidence from randomised clinical trials for the effectiveness of rivaroxaban against standard anticoagulation practice.. The implementation of a search strategy in the Journal of Thrombosis and Haemostasis and the American Heart Association. The search identified randomised, controlled trials investigating the efficacy and safety of rivaroxaban against standard anticoagulation practice in the prevention and treatment of venous thromboembolism, which were then reviewed.. Rivaroxaban in phase II studies has shown comparable rates of efficacy and safety with enoxaparin in the prevention of venous thromboembolism. Rivaroxaban given once or twice daily over a wide dose range was as effective and safe as standard therapy for the treatment of acute, symptomatic DVT. Preliminary data in phase III studies show rivaroxaban 10 mg administered once daily is superior to enoxaparin in the prevention of venous thromboembolism.. Results from phase II trials and current on-going research demonstrates that rivaroxaban has the potential to replace standard anticoagulation practice for the prevention of venous thromboembolism.

Topics: Anticoagulants; Humans; Morpholines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Rivaroxaban (Xarelto) is a member of a new class of oral, direct (antithrombin-independent) factor Xa inhibitors, which restrict thrombin generation both in vitro and in vivo. After oral administration the absorption is near 100%, the bioavailability is near 80%, and the elimination half-life is 5-9 hours with mixed excretion via the renal and fecal/biliary routes. The pharmacokinetics of rivaroxaban are predictable and consistent with a rapid onset of antithrombotic action within 2 hours after administration. Phase II clinical studies have been carried out in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) and a dose of 10 mg once daily for thromboprophylaxis was selected for further clinical development. The results of the phase III studies showed a significantly better antithrombotic efficacy of rivaroxaban compared with enoxaparin both in the short term (10-14 days) in TKA patients and long term (35 +/- 4 days) in THA patients with a comparable safety. Symptomatic thromboembolic events were also significantly reduced with rivaroxaban. Liver enzyme elevation was seen in patients treated with rivaroxaban, but there was no indication of an increased risk of liver toxicity compared with enoxaparin. In conclusion, rivaroxaban is a potent and safe new compound for antithrombotic prophylaxis in orthopedic surgery.

Topics: Administration, Oral; Animals; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Morpholines; Orthopedic Procedures; Patient Satisfaction; Quality of Life; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Currently, pharmacological thromboprophylaxis is frequently required in patients undergoing surgery, due to the high risk of deep venous thrombosis in the perioperative period. The administration of these anticoagulant agents (in Spain, usually low molecular weight heparins or fondaparinux, and in future, probably also the new oral anticoagulants dabigatran and rivaroxaban) may conflict with regional anesthetic techniques, in which maintaining hemostatic integrity is essential. Therefore, safety protocols have been designed that allow thromboprophylaxis to be administered with optimal effectiveness and anesthetic techniques to be performed with maximal safety; these protocols are based on the drug used, as well as on the dose and time of administration. The present chapter reviews the details related to these issues.

Topics: Acenocoumarol; Administration, Oral; Anesthesia, Conduction; Anticoagulants; Benzimidazoles; Clinical Protocols; Dabigatran; Early Ambulation; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Risk Factors; Rivaroxaban; Safety; Surgical Procedures, Operative; Thiophenes; Venous Thromboembolism; Venous Thrombosis

In Western countries, venous thromboembolism (VTE) is a widespread and serious disorder, with hospital admission rates that appear to be increasing. Current anticoagulant therapies available for the prevention and treatment of VTE have several drawbacks that make them either difficult to manage effectively, due to a need for careful monitoring to control coagulation, or, in the case of parenterally administered agents, inconvenient for long-term use. To address some of these issues, new anticoagulants are in clinical development that can be orally administered and directly target specific factors in the coagulation cascade. This article reviews the rationale behind development of these novel agents and provides a critical appraisal of their clinical potential. In addition, the impact that the introduction of such agents into clinical practice would have is discussed from the patient perspective.

Topics: Administration, Oral; Benzimidazoles; Blood Coagulation; Dabigatran; Fibrinolytic Agents; Hemorrhage; History, 20th Century; History, 21st Century; Humans; Medication Adherence; Morpholines; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into 2 stages: Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This article (1) reviews the pharmacology of these agents, (2) outlines their potential strengths and weaknesses, (3) describes the results of clinical trials with these new drugs, and (4) identifies the evolving role of new anticoagulants in the management of VTE.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dabigatran; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Male; Maximum Tolerated Dose; Morpholines; Oligosaccharides; Postphlebitic Syndrome; Prognosis; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Survival Analysis; Thiophenes; Treatment Outcome; Venous Thromboembolism

Indirect systemic and direct oral factor Xa and direct oral factor IIa inhibitors with improved pharmacologic profiles compared with heparins and vitamin K antagonists are currently in clinical development. This overview focuses on the indirect antithrombin dependent pentasaccharide derivatives of idraparinux and on the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran). Specifically, the results of dose-finding studies for the prevention of venous thromboembolism after elective orthopedic surgery, the results of dose-finding studies for treatment of acute venous thromboembolism including prolonged prophylaxis of recurrent events, and the designs of ongoing clinical trials are reviewed.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Azetidines; Benzimidazoles; Benzylamines; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Glycine; Humans; Infusions, Parenteral; Morpholines; Oligosaccharides; Piperazines; Prothrombin; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombin; Thrombosis; Venous Thromboembolism

The evaluation and management of patients who sustain recurrent thromboembolic events while taking therapeutic anticoagulation have not been well characterized; moreover, there has been no systematic review or randomized trial focused on treating patients with recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) during anticoagulant treatment. Therefore, we developed a pilot trial to compare rivaroxaban plus aspirin versus acenocoumarol in patients with recurrent venous thromboembolism despite ongoing anticoagulation with rivaroxaban.. The study was a multicenter, randomized clinical trial. We randomly assigned patients with objectively documented recurrent venous thromboembolism to receive rivaroxaban (20 mg once a day) plus aspirin (300 mg once a day) or an adjusted dose of acenocoumarol. The study was designed to evaluate the incidence of recurrent thromboembolic events (recurrent ipsilateral or contralateral DVT, PE, ischemic stroke, and myocardial infarction) and hemorrhagic events.. A total of 58 patients were randomized: 28 were allocated to the rivaroxaban plus aspirin group and 30 to the acenocoumarol group. After 90 days of follow-up, three recurrent thromboembolic events (primary outcome) occurred in the acenocoumarol group - two DVTs and one ischemic stroke - and zero events in the rivaroxaban plus aspirin group (risk ratio [RR] 0.15; 95 % confidence interval [CI] 0.008-2.83; P = 0.20). Minor bleeding occurred in five patients in the acenocoumarol group and zero in the rivaroxaban plus aspirin group (RR 0.09; 95 % CI 0.005-1.68; p = 0.10). There was one non-fatal gastrointestinal major bleed in the rivaroxaban plus aspirin group.. In this pilot study, there were no significant differences in any outcome assessed; however, recurrent thromboembolic events and minor bleeding events occurred numerically less frequently in the rivaroxaban plus aspirin group. These data suggest the need to carry out more extensive randomized studies with sufficient statistical power to clarify these results.

Topics: Acenocoumarol; Anticoagulants; Aspirin; Hemorrhage; Humans; Ischemic Stroke; Pilot Projects; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Tranexamic acid (TXA) has been widely applied in total knee arthroplasty (TKA) to significantly reduce perioperative blood loss and improve knee function recovery in patients after surgery. The choice of antithrombotic agents for venous thromboembolism (VTE) prevention after TKA is controversial. Therefore, this study aimed to compare the effects of different antithrombotic agents on patients after primary unilateral TKA in the context of applied TXA.. A total of 180 patients undergoing primary unilateral TKA from October 2020 to December 2021 were included in this study. All patients were given an intraoperative drip of 60 mg/kg TXA. Thereafter, patients were divided into three groups (n = 60 each). Baseline data were comparable among the three groups. The average follow-up time was 3.02 ± 0.09 months. Group 1 enrolled patients receiving oral rivaroxaban (RA) at 10 mg, Group 2 included patients who received subcutaneous Dalteparin sodium at 2500 IU, while Group 3 included patients taking oral aspirin (ASA) at 100 mg. Patients in all the three groups received treatment once a day for 30 days at 12 h postoperatively. The primary outcomes in this study were post-treatment drainage volume and thrombotic complication rate. The secondary outcomes included hematologic parameters, transfusion rate, intraoperative blood loss, total blood loss (TBL), and bleeding complication rate.. The average drainage volume after treatment was significantly lower in Group 3 than in Group 1 and Group 2 (205.2 ± 69.0 vs 243.4 ± 72.5 vs 295.4 ± 72.5 ml, P < 0.001), and there was a significant difference between Group 1 and Group 2 (243.4 ± 72.5 mL vs 295.4 ± 72.5 mL, P < 0.001). The blood transfusion rate of Group 2 dramatically increased compared with Group 1 and Group 3 (20.0% vs 6.7% vs 5.0%, P = 0.01). The bleeding complication rate in Group 1 apparently increased relative to Group 2 and Group 3 (26.7% vs 10.0% vs 8.3%, P = 0.008). Besides, there was no significant difference in the thrombotic complication rate among the three groups.. Under the background of TXA application, ASA, RA, and Dalteparin sodium were all effective on preventing VTE after TKA. In addition, ASA effectively reduced post-treatment Hemoglobin (Hb) loss, drainage volume, TBL, transfusion rate, and bleeding complications compared with RA and Dalteparin sodium.. The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200060169). Date of Registration: 21/05/2022.

Topics: Anticoagulants; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Dalteparin; Fibrinolytic Agents; Humans; Postoperative Hemorrhage; Prospective Studies; Rivaroxaban; Tranexamic Acid; Venous Thromboembolism

The benefit of rivaroxaban in thromboprophylaxis after oncologic lung surgery remains unknown. To evaluate the efficacy and safety of rivaroxaban, patients who underwent thoracic surgery for lung cancer were enrolled, and randomly assigned to rivaroxaban or nadroparin groups in a 1:1 ratio; anticoagulants were initiated 12-24 h after surgery and continued until discharge. Four hundred participants were required according to a noninferiority margin of 2%, assuming venous thromboembolism (VTE) occurrence rates of 6.0% and 12.6% for patients in the rivaroxaban and nadroparin groups, respectively. The primary efficacy outcome was any VTE during the treatment and 30-day follow-up periods. The safety outcome was any on-treatment bleeding event. Finally, 403 patients were randomized (intention-to-treat [ITT] population), with 381 included in per-protocol (PP) population. The primary efficacy outcomes occurred in 12.5% (25/200) of the rivaroxaban group and 17.7% (36/203) of the nadroparin group (absolute risk reduction, -5.2%; 95% confidence interval [CI], [-12.2-1.7]), indicating the noninferiority of rivaroxaban in ITT population. Sensitivity analysis was performed in the PP population and yielded similar results, confirming the noninferiority of rivaroxaban. In the safety analysis population, the incidence of any on-treatment bleeding events did not differ significantly between the groups (12.2% for rivaroxaban vs. 7.0% for nadroparin; relative risk [RR], 1.9; 95% CI, [0.9-3.7]; p = .08), including major bleeding (9.7% vs. 6.5%; RR, 1.6 [95% CI, 0.9-3.7]; p = .24), and nonmajor bleeding (2.6% vs. 0.5%; RR, 5.2 [95% CI, 0.6-45.2]; p = .13). Rivaroxaban for thromboprophylaxis after oncologic lung surgery was shown to be noninferior to nadroparin.

Topics: Anticoagulants; Hemorrhage; Humans; Lung Neoplasms; Nadroparin; Rivaroxaban; Thoracic Surgery; Venous Thromboembolism

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality after bariatric surgery. Clinical end point studies on thromboprophylaxis with direct oral anticoagulants in patients undergoing bariatric surgery are lacking.. To assess the efficacy and safety of a prophylactic dose of 10 mg/d of rivaroxaban for both 7 and 28 days after bariatric surgery.. This assessor-blinded, phase 2, multicenter randomized clinical trial was conducted from July 1, 2018, through June 30, 2021, with participants from 3 academic and nonacademic hospitals in Switzerland.. Patients were randomized 1 day after bariatric surgery to 10 mg of oral rivaroxaban for either 7 days (short prophylaxis) or 28 days (long prophylaxis).. The primary efficacy outcome was the composite of deep vein thrombosis (symptomatic or asymptomatic) and pulmonary embolism within 28 days after bariatric surgery. Main safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and mortality.. Of 300 patients, 272 (mean [SD] age, 40.0 [12.1] years; 216 women [80.3%]; mean body mass index, 42.2) were randomized; 134 received a 7-day and 135 a 28-day VTE prophylaxis course with rivaroxaban. Only 1 thromboembolic event (0.4%) occurred (asymptomatic thrombosis in a patient undergoing sleeve gastrectomy with extended prophylaxis). Major or clinically relevant nonmajor bleeding events were observed in 5 patients (1.9%): 2 in the short prophylaxis group and 3 in the long prophylaxis group. Clinically nonsignificant bleeding events were observed in 10 patients (3.7%): 3 in the short prophylaxis arm and 7 in the long prophylaxis arm.. In this randomized clinical trial, once-daily VTE prophylaxis with 10 mg of rivaroxaban was effective and safe in the early postoperative phase after bariatric surgery in both the short and long prophylaxis groups.. ClinicalTrials.gov Identifier: NCT03522259.

Topics: Adult; Anticoagulants; Female; Hemorrhage; Humans; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization.. COVID-PREVENT, an open-label, multicenter, randomized, clinical trial enrolled patients (≥ 18 years) with moderate to severe COVID-19 and age-adjusted D-dimers > 1.5 upper limit of normal (ULN). The participants were randomly assigned (1:1) to receive either therapeutic anticoagulation with rivaroxaban 20 mg once daily or thromboprophylaxis with a heparin (SOC) for at least 7 days followed by prophylactic anticoagulation with rivaroxaban 10 mg once daily for 28 days or no thromboprophylaxis. The primary efficacy outcome was the D-dimer level and the co-primary efficacy outcome the 7-category ordinal COVID-19 scale by WHO at 7 days post randomization. The secondary outcome was time to the composite event of either venous or arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause death or progression to intubation and invasive ventilation up to 35 days post randomization.. The primary efficacy outcome D-dimer at 7 days was not different between patients assigned to therapeutic (n = 55) or prophylactic anticoagulation (n = 56) (1.21 mg/L [0.79, 1.86] vs 1.27 mg/L [0.79, 2.04], p = 0.78). In the whole study population D-dimer was significantly lower at 7 days compared to baseline (1.05 mg/L [0.75, 1.48] vs 1.57 mg/L [1.13, 2.19], p < 0.0001). Therapy with rivaroxaban compared to SOC was not associated an improvement on the WHO 7-category ordinal scale at 7 days (p = 0.085). Rivaroxaban improved the clinical outcome measured by the score in patients with a higher baseline D-dimer  > 2.0 ULN (exploratory analysis; 0.632 [0.516, 0.748], p = 0.026). The secondary endpoint occurred in 6 patients (10.9%) in the rivaroxaban group and in 12 (21.4%) in the SOC group (time-to-first occurrence of the components of the secondary outcome: HR 0.5; 95% CI 0.15-1.67; p = 0.264). There was no difference in fatal or non-fatal major or clinically relevant non-major bleeding between the groups.. Therapeutic anticoagulation with rivaroxaban compared to prophylactic anticoagulation with a heparin did not improve surrogates of clinical outcome in patients with moderate to severe COVID-19. Whether initial rivaroxaban at therapeutic doses might be superior to thromboprophylaxis in patients with COVID-19 and a high risk as defined by D-dimer  > 2 ULN needs confirmation in further studies.

Topics: Anticoagulants; COVID-19; Heparin; Humans; Rivaroxaban; SARS-CoV-2; Treatment Outcome; Venous Thromboembolism

Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes.. This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365.. Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180.. Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time.. URL: https://www.. gov; Unique identifier: NCT03178864.

Topics: Adolescent; Adult; Anticoagulants; Canada; Feasibility Studies; Female; Headache; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Prospective Studies; Quality of Life; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

The post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency due to a prior ipsilateral deep venous thrombosis (DVT). This is a frequent complication that develops in 20%-50% of patients after a proximal DVT and is associated with significant healthcare, economic and societal consequences. In the absence of effective and well-tolerated treatment options for established PTS, effective preventative measures are needed. Anticoagulation itself reduces the risk of PTS, and low-molecular-weight heparin may reduce this further through anti-inflammatory properties targeting the initial acute inflammatory phase of DVT.. The Tinzaparin Lead-In to Prevent the Post-Thrombotic syndrome pilot trial is an investigator-initiated, multicentre, open-label assessor-blinded trial that will randomise patients with first acute symptomatic common femoral or iliac DVT to receive either a 3-week lead-in course of tinzaparin, followed by rivaroxaban (experimental arm) or rivaroxaban alone (control arm). Its primary objectives are to assess: (1) proportion of PTS at 6 months using the Villalta scale and (2) study feasibility, which consists of (a) the proportion of screened patients eligible for the study, (2) the proportion of eligible patients recruited and (c) the proportion of recruited patients adherent to treatment (defined as at least 80% of drug taken). This study will determine the feasibility of a subsequent larger definitive trial. Secondary outcomes include change of quality of life scores, PTS severity, global improvement, patient satisfaction, bleeding, recurrent venous thromboembolism, leg pain, death and lost to follow-up. Target recruitment will be a total of 60 participants, recruited at 5-6 centres.. Primary ethics approval was received from the Sunnybrook Health Sciences Center Research Ethics Board (approval ID 3315). Results of the study will be disseminated via peer-reviewed presentation at scientific conferences and open access publication.. NCT04794569.

Topics: Anticoagulants; Humans; Pilot Projects; Postthrombotic Syndrome; Quality of Life; Randomized Controlled Trials as Topic; Rivaroxaban; Tinzaparin; Treatment Outcome; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE.. Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE?. In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months.. Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97).. In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided.. ClinicalTrials.gov; No.: NCT02746185; URL: www.. gov.

Topics: Aged; Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown.. In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684.. From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group.. In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis.. Bayer.

Topics: Adult; Aftercare; Aged; Blood Coagulation; COVID-19; COVID-19 Drug Treatment; Factor Xa Inhibitors; Female; Heparin; Hospitalization; Humans; Male; Middle Aged; Patient Discharge; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

BACKGROUND Venous thrombosis (VTE) is a common adverse event among inpatients, which can cause pulmonary embolism, and greatly increases mortality. The effects of rivaroxaban in patients undergoing brain glioma surgery have still not been explored. This single-center study of 94 patients undergoing surgery for cerebral glioma aimed to compare postoperative thromboprophylaxis with and without rivaroxaban. MATERIAL AND METHODS We designed a randomized, controlled, double-blind study to evaluate the effect of rivaroxaban on 94 patients undergoing brain glioma surgery. These patients were divided into a rivaroxaban group (administered at 10 mg per day from admission to discharge) and a placebo group. The primary study endpoint was incidence of VTE at discharge. The secondary endpoints included safety outcomes of major bleeding, allergy, or VTE-related death. RESULTS A total of 94 patients were enrolled in the study: 47 in the rivaroxaban group and 47 in the placebo group. Baseline characteristics of participants were well-matched in both groups. A significant reduction was found in the incidence of VTE in the rivaroxaban treatment group versus the placebo group (1/47 vs 10/47 patients, P=0.008). The rate of major bleeding events was quite low in both group (1/47 vs 1/47 patients). One patient in the placebo group died due to a pulmonary embolism and intractable concomitant underlying diseases. CONCLUSIONS Our results indicate that treatment with rivaroxaban is a safe and effective thromboprophylaxis treatment in patients undergoing surgery for malignant cerebral glioma.

Topics: Brain Neoplasms; Double-Blind Method; Factor Xa Inhibitors; Glioma; Humans; Middle Aged; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic isolated distal deep vein thrombosis (IDDVT). In real-world clinical practice, both therapeutic and prophylactic anticoagulation are used for acute IDDVT. However, therapeutic anticoagulation is associated with higher risk of bleeding than prophylactic anticoagulation. Thus, this study aims to assess the efficacy and safety in patients with first acute symptomatic IDDVT treated with therapeutic or prophylactic anticoagulation using rivaroxaban.. This study is a prospective, multicentre, single-blind, randomised controlled trial. Outpatients with a first, acute, symptomatic, objectively confirmed IDDVT in four centres from 1 August 2021 are recruited. Eligible patients are randomised in a 1:1 ratio to receive prophylactic anticoagulation (rivaroxaban 10 mg once a day for 3 months) or therapeutic anticoagulation (rivaroxaban 20 mg once a day for 3 months). All patients are followed for 6 months. The primary efficacy outcome is radiographically confirmed recurrent venous thromboembolism. The primary safety outcome is the incidence of major or clinically relevant non-major bleeding events.. This study has been approved by the Ethics Committee of Zhongshan Hospital Fudan University (B2021-175R). Study results will be disseminated through peer-reviewed journals.. NCT04967573.

Topics: Anticoagulants; Hemorrhage; Humans; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Single-Blind Method; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The clinical benefit of extended prophylaxis for venous thromboembolism (VTE) after laparoscopic surgery for cancer is unclear. The efficacy and safety of direct oral anticoagulants for this indication are unexplored. PROphylaxis of venous thromboembolism after LAParoscopic Surgery for colorectal cancer Study II (PROLAPS II) was a randomized, double-blind, placebo-controlled, investigator-initiated, superiority study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban after laparoscopic surgery for colorectal cancer. Consecutive patients who had laparoscopic surgery for colorectal cancer were randomized to receive rivaroxaban (10 mg once daily) or a placebo to be started at 7 ± 2 days after surgery and given for the subsequent 3 weeks. All patients received antithrombotic prophylaxis with low-molecular-weight heparin from surgery to randomization. The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT), or VTE-related death at 28 ± 2 days after surgery. The primary safety outcome was major bleeding. Patient recruitment was prematurely closed due to study drug expiry after the inclusion of 582 of the 646 planned patients. A primary study outcome event occurred in 11 of 282 patients in the placebo group compared with 3 of 287 in the rivaroxaban group (3.9 vs 1.0%; odds ratio, 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank P = .032). Major bleeding occurred in none of the patients in the placebo group and 2 patients in the rivaroxaban group (incidence rate 0.7%; 95% CI, 0-1.0). Oral rivaroxaban was more effective than placebo for extended prevention of VTE after laparoscopic surgery for colorectal cancer without an increase in major bleeding. This trial was registered at www.clinicaltrials.gov as #NCT03055026.

Topics: Anticoagulants; Colorectal Neoplasms; Fibrinolytic Agents; Hemorrhage; Humans; Laparoscopy; Rivaroxaban; Venous Thromboembolism

Prior studies have observed an association between the burden of atherosclerotic vascular disease and the risk of venous thromboembolism (VTE). The association is not well described in peripheral artery disease (PAD) after lower extremity revascularization (LER).. To describe the risk of, factors associated with, and outcomes after VTE, as well as the association of low-dose rivaroxaban plus antiplatelet therapy with VTE after LER.. This global, multicenter cohort study used data from the Vascular Outcomes Study of ASA (acetylsalicylic acid) Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD (VOYAGER PAD) randomized clinical trial, which enrolled patients from 2015 to 2018 with median follow-up of 28 months. Participants included patients with PAD undergoing LER. Patients with an indication for therapeutic anticoagulation were excluded. Data were analyzed from September 2020 to September 2021.. Randomization to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily; short-term clopidogrel was used at the discretion of the treating physician.. Symptomatic VTE was a prespecified secondary outcome and prospectively collected.. Among 6564 patients (median [IQR] age, 67 [61-73] years; 4860 [74.0%] men), 66 patients had at least 1 VTE. The 3-year rate of VTE in patients receiving placebo was 1.7%, and the pattern of risk was linear (year 1: 0.5%; year 2: 1.1%). After multivariable modeling, weight (hazard ratio [HR], 3.04; 95% CI, 1.09-8.43), hypertension (HR, 2.11; 95% CI, 0.91-4.89), prior amputation (HR, 2.07; 95% CI, 0.95-4.53), and older age (HR, 1.81; 95% CI, 1.06-3.11) were associated with increased risk of VTE. VTE was associated with risk of subsequent mortality (HR, 7.22; 95% CI, 4.66-11.19). Compared with aspirin alone, rivaroxaban plus aspirin was associated with lower VTE risk (HR, 0.61; 95% CI, 0.37-0.998; P = .047), with benefit apparent early and sustained over time. This association was not modified by use of clopidogrel at randomization (without clopidogrel: HR, 0.55; 95% CI, 0.29-1.07; with clopidogrel: HR, 0.69; 95% CI, 0.32-1.48; P for interaction = .67).. In this cohort study, there was continuous risk for VTE after LER in patients with PAD, with greater risk in patients who were older and had obesity and those with more severe PAD, as reflected by prior amputation. Low-dose rivaroxaban plus aspirin was associated with lower VTE risk compared with aspirin alone, with benefits apparent early and continued over time. The spectrum of venous and arterial thrombotic events and overall benefits of more potent antithrombotic strategies for prevention should be considered after LER for PAD.

Topics: Aged; Aspirin; Clopidogrel; Cohort Studies; Female; Humans; Lower Extremity; Male; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Venous Thromboembolism

Anticoagulant treatment of pediatric cancer-associated venous thromboembolism (VTE) has not been prospectively evaluated. Management of anticoagulation for cancer-associated VTE is often challenged by drug interactions and treatment interruptions. A total of 56 of the 500 children (11.2%) with VTE who participated in the recent EINSTEIN-Jr randomized study had cancer (hematologic malignancy, 64.3%, solid malignant tumor, 35.7%). Children were allocated to either therapeutic-dose bodyweight-adjusted oral rivaroxaban (n=40) or standard anticoagulation with heparins, with or without vitamin K antagonists (n=16) and received a median of 30 concomitant medications. Based on sparse blood sampling at steady-state, pharmacokinetic (PK) parameters of rivaroxaban were derived using population PK modeling. During the 3 months of treatment, no recurrent VTE or major bleeding occurred (95% confidence interval, 0.0%-6.4%), and 3-month repeat imaging showed complete or partial vein recanalization in 20 and 24 of 52 evaluable children (38.5% and 46.2%, respectively). Anticoagulant treatment was interrupted 70 times in 26 (46.4%) children because of thrombocytopenia, invasive procedures, or adverse events, for a mean individual period of 5.8 days. Anticoagulant therapy was resumed in therapeutic doses and was not associated with thrombotic or bleeding complications. Rivaroxaban exposures were within the adult exposure range and similar to those observed in children with VTE who did not have cancer-associated VTE. Rivaroxaban and standard anticoagulants appeared safe and efficacious and were associated with reduced clot burden in most children with cancer-associated VTE, including those who had anticoagulant treatment interruptions. Rivaroxaban exposures were within the adult exposure range despite significant polypharmacy use. This trial was registered at www.clinicaltrials.gov as #NCT02234843.

Topics: Anticoagulants; Child; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

Enoxaparin is currently used for VTE prophylaxis. Rivaroxaban is more cost-effective and is as potent as enoxaparin in VTE prophylaxis.. The study was held at Al-Zahra and Kashani university hospitals in Isfahan, Iran, from January 2019 to October 2020. Two hundred ninety-six patients requiring instrumented spine surgery were enrolled; 23 were excluded (lack of consent/interfering medical situations). They were randomized into the groups of rivaroxaban (case, n = 137) and enoxaparin receiving (control, n = 136). Medical data were recorded and 244 patients (case = 123, control = 121) were analyzed value < 0.05 was meaningful.. 150 patients were males, and 94 were females. The mean age was 52.09 ± 12.6 years. Postoperative drain volume was higher in rivaroxaban received patients than in enoxaparin (p = 0.02). Post-operation epidural hematoma was detected in 3 patients in the case and 1 in the control group, which was not meaningful(p = 0.622). All of them were evacuated surgically. POH was associated with cervical canal stenosis surgery, existing comorbidities, and new medical events. New medical events were associated with postoperative wound dehiscence (p = 0.001). Short and long-term postoperative outcomes were similar in both groups. The mean follow-up duration was 25.8 ± 7.5 months.. Rivaroxaban is as effective as enoxaparin in venous thromboembolic event prophylaxis. Regarding postoperative epidural hematoma, statistical analysis showed equal safety of both drugs. Still, the authors would like to recommend more discretion in rivaroxaban administration in cervical spine laminectomy until future studies are conducted.

Topics: Adult; Anticoagulants; Enoxaparin; Female; Hematoma; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism

Real-world evidence on factor Xa inhibitor (rivaroxaban) prescribing patterns, safety, and efficacy in patients with non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) is rare. Herein, we sought to examine the above outcomes in the largest academic center in the Kingdom of Saudi Arabia (KSA).. This is a retrospective observational study designed to examine the prescribing pattern, safety and real-world effectiveness of the factor Xa inhibitor rivaroxaban in patients with NVAF and VTE. Data on rivaroxaban prescriptions were collected and analyzed. Bleeding outcomes were defined as per the International Society on Thrombosis and Hemostasis (ISTH) definition.. A total of 2,316 patients taking rivaroxaban recruited through several departments of King Saud University Medical City (KSUMC). The mean age was 61 years (±17.8) with 55% above the age of 60 and 58% were females. Deep vein thrombosis and pulmonary embolism (VTE) was the most prevalent reason for prescribing rivaroxaban, followed by NVAF. A total daily dosage of 15 mg was given to 23% of the patients. The incidence rate of recurrent thrombosis and recurrent stroke was 0.2%. Furthermore, rivaroxaban had a 0.04 percent incidence rate of myocardial infarction. Half of the patients with recurrent thrombosis and stroke were taking 15 mg per day. The incidence rate of major bleeding was 1.1%. More over half of the patients who experienced significant bleeding were taking rivaroxaban at a dosage of 20 mg per day. According to the HAS-BLED Score (>2 score), 48 percent of patients who experienced significant bleeding had a high risk of bleeding. Non-major bleeding occurred in 0.6% of cases. Similarly, 40% of patients with non-major bleeding were taking rivaroxaban at a dosage of 20 mg per day. According to the HAS-BLED Score, just 6.6% of these individuals had a high risk of bleeding. 93.4% of the patients, on the other hand, were at intermediate risk.. The prescription of rivaroxaban in this real-life cohort study differs from the prescribing label and the outcomes of a phase 3 randomised clinical trial. However, for individuals with VTE and NVAF, the 20 mg dose looked to be more efficacious than the pivotal trial outcomes. Furthermore, among patients with VTE and NVAF, rivaroxaban was linked to a decreased incidence of safety events such as recurrent thrombosis, recurrent stroke, MI, major bleeding, and non-major haemorrhage in a real-world environment.

Topics: Anticoagulants; Antithrombin III; Atrial Fibrillation; Cohort Studies; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Saudi Arabia; Stroke; Thrombophlebitis; Venous Thromboembolism

Background Venous thromboembolism (VTE) often occurs after hospitalization in medically ill patients, but the population benefit-risk of extended thromboprophylaxis remains uncertain. Methods and Results The MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) study (NCT02111564) was a randomized double-blind trial that compared thromboprophylaxis with rivaroxaban 10 mg daily versus placebo for 45 days after hospital discharge in medically ill patients with a creatinine clearance ≥50 mL/min. The benefit-risk balance in this population was quantified by calculating the between-treatment rate differences in efficacy and safety end points per 10 000 patients treated. Clinical characteristics of the study population were consistent with a hospitalized medical population at risk for VTE. Treating 10 000 patients with rivaroxaban resulted in 32.5 fewer symptomatic VTE and VTE-related deaths but was associated with 8 additional major bleeding events. The treatment benefit was driven by the prevention of nonfatal symptomatic VTE (26 fewer events). There was no between-treatment difference in the composite of critical site or fatal bleeding. Conclusions Extending thromboprophylaxis with rivaroxaban for 45 days after hospitalization provides a positive benefit-risk balance in medically ill patients at risk for VTE who are not at high risk for bleeding. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02111564.

Topics: Aftercare; Anticoagulants; Creatinine; Hemorrhage; Hospitalization; Humans; Patient Discharge; Risk Assessment; Rivaroxaban; Venous Thromboembolism

To determine whether there is a difference in orthopaedic trauma patient medication satisfaction and adherence using an oral versus subcutaneous injectable anticoagulant for venous thromboembolism chemoprophylaxis.. Randomized controlled trial.. Single academic Level 1 trauma center.. One hundred twenty adult orthopaedic trauma patients with operative pelvic or lower extremity fractures were randomized and completed the study.. Three weeks of either the service standard 40 mg once daily enoxaparin versus trial medication 10 mg once daily rivaroxaban postoperatively.. Patient satisfaction as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9). Medication adherence as measured by the Morisky Medication Adherence Scale (MMAS-8).. Medication adherence was similar in both groups. Medication satisfaction was significantly higher in the oral rivaroxaban group based on the TSQM-9 and patient-reported data. Secondary outcomes found no significant difference in the incidence of bleeding events or clinically relevant venous thromboembolism. The enoxaparin group experienced more adverse medication-related events. The rivaroxaban medication regimen costs 7.5-10× less out of pocket for uninsured patients.. The results of this randomized controlled trial demonstrate that patients with surgical orthopaedic trauma prefer an oral anticoagulant for postoperative venous thromboembolism chemoprophylaxis and suggest that rivaroxaban may be a viable option. Furthermore, large-scale studies are needed to confirm safety and efficacy for rivaroxaban in this population as a potential alternative to enoxaparin and aspirin.. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Topics: Adult; Anticoagulants; Enoxaparin; Humans; Orthopedics; Prospective Studies; Rivaroxaban; Venous Thromboembolism

To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT).. Randomised, double blind, placebo controlled clinical trial.. 28 outpatient clinics specialising in venous thromboembolism.. 402 adults (≥18 years) with symptomatic isolated distal DVT.. After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion.. The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes.. 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred.. Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage.. EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447.

Topics: Adult; Anticoagulants; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Background Patients with single-ventricle physiology who undergo the Fontan procedure are at risk for thrombotic events associated with significant morbidity and mortality. The UNIVERSE Study evaluated the efficacy and safety of a novel liquid rivaroxaban formulation, using a body weight-adjusted dosing regimen, versus acetylsalicylic acid (ASA) in children post-Fontan. Methods and Results The UNIVERSE Study was a randomized, multicenter, 2-part, open-label study of rivaroxaban, in children who had undergone a Fontan procedure, to evaluate its dosing regimen, safety, and efficacy. Part A was the single-arm part of the study that determined the pharmacokinetics/pharmacodynamics and safety of rivaroxaban in 12 participants before proceeding to part B, whereby 100 participants were randomized 2:1 to open-label rivaroxaban versus ASA. The study period was 12 months. A total of 112 participants were enrolled across 35 sites in 10 countries. In part B, for safety outcomes, major bleeding occurred in one participant on rivaroxaban (epistaxis that required transfusion). Clinically relevant nonmajor bleeding occurred in 6% of participants on rivaroxaban versus 9% on ASA. Trivial bleeding occurred in 33% of participants on rivaroxaban versus 35% on ASA. For efficacy outcomes, 1 participant on rivaroxaban in part B had a pulmonary embolism (2% overall event rate); and for ASA, 1 participant had ischemic stroke and 2 had venous thrombosis (9% overall event rate). Conclusions In this study, participants who received rivaroxaban for thromboprophylaxis had a similar safety profile and fewer thrombotic events, albeit not statistically significant, compared with those in the ASA group. Registration URL: https://www.clinicaltrials.gov. Identifier: NCT02846532.

Topics: Anticoagulants; Aspirin; Child; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Stroke; Thrombosis; Venous Thromboembolism

Topics: Aftercare; Anticoagulants; Enoxaparin; Hemorrhage; Hospitalization; Humans; Patient Discharge; Risk Factors; Rivaroxaban; Venous Thromboembolism

Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.. Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications.. We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ2 = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ2 = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5-1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4-1740.6mL]) (χ2 = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8-83.0], Rivaroxaban: 81.0 [79.3-83.0], χ2 = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0-92.0], Rivaroxaban: 91.5 [88.3-92.8], χ2 = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ2 = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ2 = 1.13, P = 0.29).. In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.. Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Humans; Rivaroxaban; Venous Thromboembolism

For the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA.. In 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS).. The primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed.. A multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding.. NCT01431456.

Topics: Activities of Daily Living; Anticoagulants; Arthroplasty, Replacement, Knee; Dabigatran; Female; Humans; Nadroparin; Netherlands; Pilot Projects; Postoperative Care; Postoperative Complications; Quality of Life; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established.. PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events.. PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

Topics: Adult; Cause of Death; COVID-19; Double-Blind Method; Extremities; Factor Xa Inhibitors; Female; Hemorrhage; Hospital Mortality; Hospitalization; Humans; Ischemia; Ischemic Stroke; Male; Middle Aged; Myocardial Infarction; Outpatients; Placebos; Rivaroxaban; Thrombosis; Venous Thromboembolism

It is unknown whether differences in clot structure and resolution contribute to the reported risk differences of recurrent venous thromboembolism (VTE) between men and women.. We used data from the EINSTEIN-PE study, a randomized, multicenter, non-inferiority study in which patients 18 years and older with acute symptomatic pulmonary embolism (PE) were randomized to rivaroxaban or enoxaparin followed by a vitamin K antagonist. PE was diagnosed by computed tomography pulmonary angiography scan or high-probability ventilation/perfusion scintigraphy. Three weeks after randomization a follow-up scan was performed. An independent adjudication committee assessed the degree of vascular obstruction.. A total of 371 participants including 174 (46.9%) women and 197 (53.0%) men were included in the present analysis. At 3 weeks, there was no difference between men and women in complete clot resolution: 39.6% and 40.2%, respectively. The absolute reduction in pulmonary vascular obstruction at week 3 was also similar: 12.9% (95% confidence interval [CI]: 11.6-14.2) in men and 12.1% (95% CI: 10.4-13.7) in women, corresponding to a resolution ratio of 0.29 (95% CI: 0.24-0.33) and 0.35 (95% CI: 0.28-0.42), respectively. No differences in clot resolution were observed between men and women diagnosed with acute PE at 3 weeks after start of anticoagulant therapy. These findings suggest that the reported higher rate of VTE recurrence in men cannot be explained by decreased clot resolution.

Topics: Adolescent; Adult; Anticoagulants; Female; Humans; Male; Pulmonary Embolism; Recurrence; Rivaroxaban; Thrombosis; Venous Thromboembolism

The objective was to test if low-risk emergency department patients with vitamin K antagonist (venous thromboembolism [VTE]; including venous thrombosis and pulmonary embolism [PE]) can be safely and effectively treated at home with direct acting oral (monotherapy) anticoagulation in a large-scale, real-world pragmatic effectiveness trial.. This was a single-arm trial, conducted from 2016 to 2019 in accordance with the Standards for Reporting Implementation Studies guideline in 33 emergency departments in the United States. Participants had newly diagnosed VTE with low risk of death based upon either the modified Hestia criteria, or physician judgment plus the simplified PE severity index score of zero, together with nonhigh bleeding risk were eligible. Patients had to be discharged within 24 hours of triage and treated with either apixaban or rivaroxaban. Effectiveness was defined by the primary efficacy and safety outcomes, image-proven recurrent VTE and bleeding requiring hospitalization >24 hours, respectively, with an upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0% for both outcomes.. We enrolled 1421 patients with complete outcomes data, including 903 with venous thrombosis and 518 with PE. The recurrent VTE requiring hospitalization occurred in 14/1421 (1.0% [95% CI, 0.5%-1.7%]), and bleeding requiring hospitalization occurred in 12/1421 (0.8% [0.4%-1.5%). The rate of severe bleeding using International Society for Thrombosis and Haemostasis criteria was 2/1421 (0.1% [0%-0.5%]). No patient died, and serious adverse events occurred in 2.5% of venous thrombosis patients and 2.3% of patients with PE. Medication nonadherence was reported by patients in 8.0% (6.6%-9.5%) and was associated with a risk ratio of 6.0 (2.3-15.2) for VTE recurrence. Among all patients diagnosed with VTE in the emergency department during the period of study, 18% of venous thrombosis patients and 10% of patients with PE were enrolled.. Monotherapy treatment of low-risk patients with venous thrombosis or PE in the emergency department setting produced a low rate of bleeding and VTE recurrence, but may be underused. Patients with venous thrombosis and PE should undergo risk-stratification before home treatment. Improved patient adherence may reduce rate of recurrent VTE. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03404635.

Topics: Anticoagulants; Emergency Service, Hospital; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Although older patients are at increased risk for venous thromboembolism (VTE), thromboprophylaxis is underused because of bleeding concerns. The MARINER trial evaluated whether rivaroxaban reduced symptomatic postdischarge VTE in acutely ill medical patients.. We hypothesized that rivaroxaban would have a favorable benefit/risk profile in patients ≥75 years of age.. Patients were randomized in a double-blind manner at hospital discharge to rivaroxaban (10 mg/day for creatinine clearance ≥50 ml/min; 7.5 mg/day for ≥30-<50 ml/min) or placebo for 45 days. Using a Cox proportional hazard model including treatment as a covariate, we compared the risk of the primary efficacy outcome (symptomatic VTE plus VTE-related death in the intention-to-treat population) and safety outcome (International Society on Thrombosis and Haemostasis major bleeding in the safety population) in the prespecified subgroups of patients ≥ and <75 years of age.. The primary event rate in patients ≥75 years of age was 2-fold higher than that in those <75 years. The incidence of the primary efficacy outcomes in both age groups was numerically lower with rivaroxaban than with placebo (≥75: 1.2% and 1.6%, HR 0.73, 95% CI 0.43-1.22; <75 0.6% and 0.8%, HR 0.78, 95% CI 0.46-1.32; interaction p-value for age group = .85). The incidence of major bleeding was low and similar in the two age and treatment groups (interaction p value for age group = .35).. Symptomatic VTE and VTE-related death occur frequently in older patients with acute medical illness. The benefit/risk profile of rivaroxaban in patients ≥75 years of age appears consistent with that observed in the general population.

Topics: Aftercare; Aged; Anticoagulants; Humans; Patient Discharge; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism.. In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed.. From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11-1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51-6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths.. In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants.. Bayer AG and Janssen Research & Development.

Topics: Adolescent; Anticoagulants; Child; Child, Preschool; Female; Humans; Infant; Male; Risk Factors; Rivaroxaban; Venous Thromboembolism

The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is undefined. Extended prophylaxis with rivaroxaban is effective in reducing post-operative VTE after major orthopedic surgery without safety concern.. PROLAPS II is an investigator-initiated, randomized, double-blind study aimed at assessing the efficacy and safety of extended antithrombotic prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer in patients who had received antithrombotic prophylaxis with low molecular-weight heparin for 7 ± 2 days (NCT03055026). Patients are randomized to receive rivaroxaban (10 mg once daily) or placebo for 3 weeks (up to day 28 ± 2 from surgery). The primary study outcome is a composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT or VTE-related death at 28 ± 2 days from laparoscopic surgery. The primary safety outcome is major bleeding defined according to the International Society of Thrombosis and Haemostasis. Symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT, major bleeding or death by day 28 ± 2 and by day 90 from surgery are secondary outcomes. Assuming an 8% event rate with placebo and 60% reduction in the primary study outcome with rivaroxaban, 323 patients per group are necessary to show a statistically significant difference between the study groups.. The PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by answering the question on the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer.

Topics: Anticoagulants; Colorectal Neoplasms; Fibrinolytic Agents; Humans; Laparoscopy; Rivaroxaban; Venous Thromboembolism

Patients with renal impairment are at higher risk of thrombosis and bleeding than those with normal renal function. The optimal rivaroxaban dose for thromboprophylaxis in acutely ill medical patients with renal impairment is unknown. MARINER and MAGELLAN were multicenter, randomized clinical trials of rivaroxaban in acutely ill medical patients. Efficacy and safety outcomes in patients with renal impairment in MARINER (7.5 mg once daily) were compared with those in patients with normal renal function in MARINER (10 mg once daily) and in a subpopulation of MAGELLAN that excluded patients at high risk for bleeding at baseline (10 mg once daily). Compared with enoxaparin/placebo in the MAGELLAN subpopulation, the relative risk (RR) of symptomatic venous thromboembolism (VTE) and VTE-related death with rivaroxaban 10 mg in patients with renal impairment (RR = 0.62; 95% confidence interval [CI] 0.27-1.44) was similar to that in those with normal renal function (RR = 0.78; 95% CI 0.44-1.40), while in MARINER, the 7.5 mg dose did not reduce the risk in patients with renal impairment (hazard ratio = 1.00; 95% CI 0.52-1.92). Major bleeding with rivaroxaban 10 mg once daily was higher in patients with renal impairment than in those with normal renal function in MAGELLAN (1.54% vs. 0.98%) and in the MAGELLAN subpopulation (0.94% vs. 0.61%). At a dose of 10 mg once daily, rivaroxaban is effective for thromboprophylaxis in acutely ill medical patients with impaired or normal renal function. The safety of this regimen is enhanced without loss of efficacy by excluding patients at high risk for bleeding, but not by using a reduced-dose strategy. TRIAL REGISTRATION:  ClinicalTrials.gov identifiers: NCT00571649 for the MAGELLAN trial, NCT02111564 for the MARINER trial.

Topics: Acute Disease; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Hemorrhage; Humans; Incidence; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Risk Factors; Rivaroxaban; Thrombosis; Treatment Outcome; Venous Thromboembolism

The Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT-D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation.. To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months.. In SELECT-D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited.. Ninety-two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06-1.58). The major and clinically relevant non-major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1-18) and 4% (95% CI, 1-17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT-negative cohort (P = .03).. The SELECT-D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.

Topics: Anticoagulants; Humans; Neoplasms; Random Allocation; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients.. In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding.. A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P<0.001 for noninferiority; P = 0.01 for superiority). The incidence of bleeding did not differ significantly between the rivaroxaban group and the enoxaparin group (1.1% and 1.0%, respectively, for major bleeding or nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding).. Rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilization after nonmajor orthopedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.).

Topics: Administration, Oral; Adult; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Hemorrhage; Humans; Injections, Subcutaneous; Lower Extremity; Male; Middle Aged; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Recently, the randomized EINSTEIN-Jr study showed similar efficacy and safety for rivaroxaban and standard anticoagulation for treatment of pediatric venous thromboembolism (VTE). The rivaroxaban dosing strategy was established based on phase 1 and 2 data in children and through pharmacokinetic (PK) modeling.. Rivaroxaban treatment with tablets or the newly developed granules-for-oral suspension formulation was bodyweight-adjusted and administered once-daily, twice-daily, or thrice-daily for children with bodyweights of ≥30, ≥12 to <30, and <12 kg, respectively. Previously, these regimens were confirmed for children weighing ≥20 kg but only predicted in those <20 kg. Based on sparse blood sampling, the daily area under the plasma concentration-time curve [AUC. Of the 335 children (aged 0-17 years) allocated to rivaroxaban, 316 (94.3%) were evaluable for PK analyses. Rivaroxaban exposures were within the adult exposure range. No clustering was observed for any of the PK parameters with efficacy, bleeding, or adverse event outcomes. Results were similar for the tablet and suspension formulation. Acceptability and palatability of the suspension were favorable.. Based on this analysis and the recently documented similar efficacy and safety of rivaroxaban compared with standard anticoagulation, we conclude that bodyweight-adjusted pediatric rivaroxaban regimens with either tablets or suspension are validated and provide for appropriate treatment of children with VTE.

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Hemorrhage; Humans; Infant; Infant, Newborn; Rivaroxaban; Venous Thromboembolism

Anticoagulant plasma concentrations and patient characteristics might affect the benefit-risk balance of therapy. The study objective was to assess the impact of model-predicted rivaroxaban exposure and patient characteristics on outcomes in patients receiving rivaroxaban for venous thromboembolism (VTE) prophylaxis (VTE-P) after hip/knee replacement surgery. Post hoc exposure-response analyses were conducted using data from the phase 3 RECORD1-4 studies, in which 12,729 patients were randomized to rivaroxaban 10 mg once daily or enoxaparin for ≤ 39 days. Multivariate regression approaches were used to correlate model-predicted individual rivaroxaban exposures and patient characteristics with outcomes. In the absence of measured rivaroxaban exposure, exposure estimates were predicted based on individual increases in prothrombin time (PT) and by making use of the known correlation between rivaroxaban plasma concentration and dynamics of PT. No significant associations between rivaroxaban exposure and total VTE or major bleeding were identified. A significant association between exposure and a composite of major or non-major clinically relevant (NMCR) bleeding from day 4 after surgery was observed. The relationship was shallow, with an approximate predicted absolute increase in a composite of major or NMCR bleeding from 1.08 [95% confidence interval (CI) 0.76-1.54] to 2.18% (95% CI 1.51-3.17) at the 5th and 95th percentiles of trough plasma concentration, respectively. In conclusion, based on the underlying data and analysis, no reliable target window for exposure with improved benefit-risk could be identified within the investigated exposure range. Hence, monitoring rivaroxaban levels is unlikely to be beneficial in VTE-P.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Biomarkers, Pharmacological; Chemoprevention; Drug Monitoring; Female; Hemorrhage; Humans; Male; Middle Aged; Models, Statistical; Postoperative Complications; Prognosis; Prothrombin Time; Risk Adjustment; Risk Assessment; Rivaroxaban; Venous Thromboembolism

Anticoagulant plasma concentrations and patient characteristics might affect the benefit-risk balance of therapy. This study assessed the impact of model-predicted rivaroxaban exposure and patient characteristics on outcomes in patients receiving rivaroxaban for venous thromboembolism treatment (VTE-T) using data from the phase 3 EINSTEIN-DVT and EINSTEIN-PE studies. In the absence of measured rivaroxaban exposure, exposure estimates were predicted based on individual increases in prothrombin time (PT) and the known correlation between rivaroxaban plasma concentrations and PT dynamics. The composite efficacy outcomes evaluated were recurrent deep-vein thrombosis (DVT) and pulmonary embolism (PE) and recurrent DVT, PE and all-cause death; safety outcomes were major bleeding and the composite of major or non-major clinically relevant (NMCR) bleeding. Exposure-response relationships were evaluated using multivariate logistic and Cox regression for the twice-daily (BID) and once-daily (OD) dosing periods, respectively. Predicted rivaroxaban exposure and CrCl were significantly associated with both efficacy outcomes in the BID period. In the OD period, exposure was significantly associated with recurrent DVT and PE but not recurrent DVT, PE and all-cause death. The statistically significant exposure-efficacy relationships were shallow. Exposure-safety relationships were absent within the investigated exposure range. During both dosing periods, low baseline hemoglobin and prior bleeding were associated with the composite of major or NMCR bleeding. In conclusion, based on the underlying data and analysis, no reliable target window for exposure with improved benefit-risk could be identified within the investigated exposure range. Therefore, monitoring rivaroxaban levels is unlikely to be beneficial in VTE-T.

Topics: Anticoagulants; Biomarkers, Pharmacological; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Models, Statistical; Prognosis; Prothrombin Time; Risk Adjustment; Risk Assessment; Rivaroxaban; Therapeutic Index; Treatment Outcome; Venous Thromboembolism

Rivaroxaban exposure and patient characteristics may affect the rivaroxaban benefit-risk balance. This study aimed to quantify associations between model-predicted rivaroxaban exposure and patient characteristics and efficacy and safety outcomes in patients with non-valvular atrial fibrillation (NVAF), using data from the phase 3 ROCKET AF trial (NCT00403767). In ROCKET AF, 14,264 patients with NVAF were randomized to rivaroxaban (20 mg once daily [OD], or 15 mg OD if creatinine clearance was 30-49 mL/min) or dose-adjusted warfarin (median follow-up: 707 days); rivaroxaban plasma concentration was measured in a subset of 161 patients. In this post hoc exposure-response analysis, a multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event efficacy and safety outcomes in 7061 and 7111 patients, respectively. There was no significant association between model-predicted rivaroxaban trough plasma concentration (C

Topics: Anticoagulants; Atrial Fibrillation; Biomarkers, Pharmacological; Chemoprevention; Drug Monitoring; Female; Hemorrhage; Humans; Male; Middle Aged; Models, Statistical; Prognosis; Prothrombin Time; Risk Adjustment; Risk Assessment; Rivaroxaban; Stroke; Venous Thromboembolism

Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown.. The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge.. MARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE). Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days. Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45. Time-to-event curves were calculated using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events.. In total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo. The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days. The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398).. Extended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding. (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564).

Topics: Acute Disease; Aftercare; Aged; Chemoprevention; Double-Blind Method; Factor Xa Inhibitors; Female; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Patient Discharge; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Pancreatic cancer patients are at risk for venous thromboembolism (VTE); the value of thromboprophylaxis has not been definitively established.. This trial randomized cancer patients initiating a new regimen and at high risk for VTE (Khorana score ≥2) to rivaroxaban 10 mg or placebo up to day 180. This analysis examined the subset of pancreatic cancer patients. The primary efficacy endpoint was the composite of symptomatic deep-vein thrombosis (DVT), asymptomatic proximal DVT, any pulmonary embolism, and VTE-related death. The primary safety endpoint was International Society on Thrombosis and Haemostasis-defined major bleeding.. In total, 49/1080 (4.5%) patients enrolled had baseline VTE on screening, with higher rates (24/362 [6.6%]) in pancreatic cancer and they were not randomized. Of 841 randomized patients, 273 (32.5%) had pancreatic cancer; 155/273 (57% in each arm) completed the double-blind period. The primary endpoint occurred in 13/135 (9.6%) patients in the rivaroxaban group and in 18/138 (13.0%) in the placebo group (hazard ratio [HR] = 0.70; 95% CI, 0.34-1.43; P = .328) in up-to-day-180 period and 5/135 (3.7%) patients receiving rivaroxaban and 14/138 (10.1%) receiving placebo in the intervention period (HR = 0.35; 95% CI, 0.13-0.97; P = .034). Major bleeding was similar (2 [1.5%] receiving rivaroxaban and 3 [2.3%] receiving placebo). Correlative biomarker studies demonstrated significant decline in D-dimer (weeks 8 and 16) in patients randomized to rivaroxaban compared to placebo (P < .01).. In ambulatory pancreatic cancer patients, rivaroxaban did not result in significantly lower incidence of VTE or VTE-related death in the 180-day period. During the intervention period, however, rivaroxaban substantially reduced VTE without increasing major bleeding, suggesting benefit of rivaroxaban prophylaxis in this setting.. ClinicalTrials.gov identifier, NCT02555878.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Incidence; Male; Middle Aged; Outpatients; Pancreatic Neoplasms; Placebos; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist). The main treatment period was 3 months. The primary efficacy outcome, symptomatic recurrent venous thromboembolism (VTE), and principal safety outcome, major or clinically relevant nonmajor bleeding,were centrally evaluated by blinded investigators. Sinus recanalization on repeat brain imaging was a secondary outcome. Statistical analyses were exploratory. In total, 114 children with confirmed CVT were randomized. All children completed the follow-up. None of the 73 rivaroxaban recipients and 1 (2.4%; CVT) of the 41 standard anticoagulant recipients had symptomatic, recurrent VTE after 3 months (absolute difference, 2.4%; 95% confidence interval [CI], -2.6% to 13.5%). Clinically relevant bleeding occurred in 5 (6.8%; all nonmajor and noncerebral) rivaroxaban recipients and in 1 (2.5%; major [subdural] bleeding) standard anticoagulant recipient (absolute difference, 4.4%; 95% CI, -6.7% to 13.4%). Complete or partial sinus recanalization occurred in 18 (25%) and 39 (53%) rivaroxaban recipients and in 6 (15%) and 24 (59%) standard anticoagulant recipients, respectively. In summary, in this substudy of a randomized trial with a limited sample size, children with CVT treated with rivaroxaban or standard anticoagulation had a low risk of recurrent VTE and clinically relevant bleeding. This trial was registered at clinicaltrials.gov as #NCT02234843.

Topics: Anticoagulants; Child; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

In the 'Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism' (SELECT-D) trial, rivaroxaban showed relatively low venous thromboembolism (VTE) recurrence but higher bleeding compared with dalteparin in patients with cancer. We aim to calculate the cost-effectiveness and budget impact of rivaroxaban compared with dalteparin in patients with cancer at risk of recurrent VTE.. We built a Markov model to calculate the cost-effectiveness from a societal perspective over a 5-year time horizon for the Dutch healthcare setting.. A hypothetical cohort of 1000 cancer patients with VTE entered the model with baseline characteristics based on the SELECT-D trial.. Six months of treatment with rivaroxaban (15 mg two times per day for first 3 weeks followed by 20 mg once daily) was compared with 6 months of treatment with dalteparin (200 IU/kg daily during month 1 followed by 150 IU/kg daily).. The primary outcome of the cost-effectiveness analysis was the incremental cost-effectiveness ratio (ICER). The robustness of the model was evaluated in probabilistic and univariate sensitivity analyses. A budget impact analysis was performed to calculate the total annual financial consequences for a societal perspective in the Netherlands.. In the base case and all scenarios, rivaroxaban were cost-saving while also slightly improving the patient's health, resulting in economically dominant ICERs. In the probabilistic sensitivity analysis, 77.8% and 98.7% of the simulations showed rivaroxaban to be cost-saving and more effective for a 5-year and 6-month time horizon, respectively. Rivaroxaban can save up to €11 326 763 (CI €5 164 254 to €17 363 231) in approximately 8000 cancer patients with VTE per year compared with dalteparin based on a 1-year time horizon.. Treatment with rivaroxaban is economically dominant over dalteparin in patients with cancer at risk for recurrent VTE in the Netherlands. The use of rivaroxaban instead of dalteparin can save over €10 million per year, primarily driven by the difference in drug costs.

Topics: Aged; Anticoagulants; Cost-Benefit Analysis; Dalteparin; Female; Humans; Male; Neoplasms; Netherlands; Rivaroxaban; Venous Thromboembolism

Rivaroxaban has been shown to be efficacious for treatment of venous thromboembolism in adults, and has a reduced risk of bleeding compared with standard anticoagulants. We aimed to develop paediatric rivaroxaban regimens for the treatment of venous thromboembolism in children and adolescents.. In this phase 2 programme, we did three studies to evaluate rivaroxaban treatment in children younger than 6 months, aged 6 months to 5 years, and aged 6-17 years. Our studies used a multicentre, single-arm design at 54 sites in Australia, Europe, Israel, Japan, and north America. We included children with objectively confirmed venous thromboembolism previously treated with low-molecular weight heparin, fondaparinux, or a vitamin K antagonist for at least 2 months or, in children who had catheter-related venous thromboembolism for at least 6 weeks. We administered rivaroxaban orally in a bodyweight-adjusted 20 mg-equivalent dose, based on physiologically-based pharmacokinetic modelling predictions and EINSTEIN-Jr phase 1 data in young adults, in either a once-daily (tablets; for those aged 6-17 years), twice-daily (in suspension; for those aged 6 months to 11 years), or three times-daily (in suspension; for those younger than 6 months) dosing regimen for 30 days (or 7 days for those younger than 6 months). The primary aim was to define rivaroxaban treatment regimens that match the target adult exposure range. The principal safety outcome was major bleeding and clinically relevant non-major bleeding. Analyses were per-protocol. The predefined efficacy outcomes were symptomatic recurrent venous thromboembolism, asymptomatic deterioration on repeat imaging at the end of the study treatment period. These trials are registered at ClinicalTrials.gov, numbers NCT02564718, NCT02309411, and NCT02234843.. Between Feb 11, 2013, and Dec 20, 2017, we enrolled 93 children (ten children younger than 6 months; 15 children aged 6 months to 1 year; 25 children aged 2-5 years; 32 children aged 6-11 years; and 11 children aged 12-17 years) into our study. 89 (96%) children completed study treatment (30 days of treatment, or 7 days in those younger than 6 months), and 93 (100%) children received at least one dose of study treatment and were evaluable for the primary endpoints. None of the children had a major bleed, and four (4%, 95% CI 1·2-10·6) of these children had a clinically relevant non-major bleed (three children aged 12-17 years with menorrhagia and one child aged 6-11 years with gingival bleeding). We found no symptomatic recurrent venous thromboembolism in any patients (0%, 0·0-3·9). 24 (32%) of 75 patients with repeat imaging had their thrombotic burden resolved, 43 (57%) patients improved, and eight (11%) patients were unchanged. No patient deteriorated. We confirmed therapeutic rivaroxaban exposures with once-daily dosing in children with bodyweights of at least 30 kg and with twice-daily dosing in children with bodyweights of at least 20 kg and less than 30 kg. Children with low bodyweights (<20 kg, particularly <12 kg) showed low exposures so, for future studies, rivaroxaban dosages were revised for these weight categories, to match the target adult exposure range. 61 (66%) of 93 children had adverse events during the study. Pyrexia was the most common adverse event (ten [11%] events), and anaemia and neutropenia or febrile neutropenia were the most frequent grade 3 or worse events (four [4%] events each). No children died or were discontinued from rivaroxaban because of adverse events.. Treatment with bodyweight-adjusted rivaroxaban appears to be safe in children. The treatment regimens that we confirmed in children with bodyweights of at least 20 kg and the revised treatment regimens that we predicted in those with bodyweights less than 20 kg will be evaluated in the EINSTEIN-Jr phase 3 trial in children with acute venous thromboembolism.. Bayer AG, Janssen Research and Development.

Topics: Adolescent; Anemia; Anticoagulants; Body Weight; Child; Child, Preschool; Drug Administration Schedule; Drug Dosage Calculations; Factor Xa; Female; Half-Life; Hemorrhage; Humans; Infant; Male; Neutropenia; Prothrombin Time; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Anticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE.. This study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications.. This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals.

Topics: Adult; Aged; Factor Xa Inhibitors; Humans; Middle Aged; Neoplasms; Rivaroxaban; Thrombosis; Venous Thromboembolism; Young Adult

Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients.. In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/ metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication.. Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died.. Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Blood Coagulation; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Neoplasms; Prospective Studies; Pulmonary Embolism; Recurrence; Republic of Korea; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

To evaluate the efficacy of the combined intravenous and intra-articular administration of tranexamic acid (TXA) to control the collateral effects and complications of rivaroxaban (RIV) after total knee arthroplasty (TKA) and to compare thromboprophylaxis schemes with and without TXA, RIV and low molecular weight heparin (LMWH).. We prospectively studied 158 TKA patients from 2014 to 2018. The patients were randomly assigned into three groups. Group A (46 patients) was administered intravenous and intra-articular TXA and RIV postoperatively; group B (58 patients) was administered TXA as in group A and LMWH postoperatively; and group C (54 patients) was administered saline as in group A and RIV postoperatively. We evaluated blood loss, transfusion requirements and hemorrhagic complications.. Hct and Hb values significantly decreased in group C compared to groups A and B, without any difference between groups A and B. Suction drain blood volume output was significantly higher in group C compared to group A and B, without any difference between group A and B. Hemorrhagic complications were more common in group C. No patient experienced clinical findings of VTE.. Combined intravenous and intra-articular administration of TXA is safe and effective in TKA, with fewer hemorrhagic complications compared to placebo. Thromboprophylaxis with RIV and LMWH is similar.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Injections, Intra-Articular; Male; Middle Aged; Postoperative Hemorrhage; Prospective Studies; Rivaroxaban; Tranexamic Acid; Treatment Outcome; Venous Thromboembolism

: To observe the effect of LMWH followed by rivaroxaban for the prevention of DVT after TKA. Between June 2015 and November 2017 as well as in accordance with the inclusion criteria, 118 patients undergoing TKA were randomly allocated to two groups. Patients in group A were applied LMWH, whereas patients in group B received LMWH followed by rivaroxaban postoperatively. The two groups were foIlowed up and compared for the incidence of DVT by color Doppler ultrasonography scan. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin (ALB), Hb and D-Dimer were also compared. No statistically significant differences of ESR, CRP, and Hb was found between the two groups (P > 0.05), while higher levels of ALB and D-D in postoperation were observed in group B (ALB: 7 and 10 days after operation, D-D: 4, 7 and 10 days after operation). The overall DVT rate of group B (46.67%) is significantly higher than that of A (25.86%; P = 0.019, η = 0.216). Moreover, the occurrence rate of DVT in group A was 18.75% (3/16) and in group B is 16.67% (3/18) (P = 0.0445, η = 0.027) for men. The DVT rate of group A and B was 28.57 and 59.52%, respectively, with statistical difference (P = 0.002, η = 0.312) for female. The DVT rate of LMWH followed by rivaroxaban group is significantly higher than that of LMWH group, especially in female group, so it is not recommend to take rivaroxaban following injection of LMWH for the prevention of DVT after TKA.

Topics: Adult; Aged; Arthroplasty, Replacement, Knee; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Middle Aged; Perioperative Care; Postoperative Care; Premedication; Rivaroxaban; Ultrasonography, Doppler; Venous Thromboembolism

Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain.. In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding.. Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49).. In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Double-Blind Method; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

The prospective, non-interventional XALIA study investigated the safety and effectiveness of rivaroxaban and standard anticoagulation for the treatment of deep vein thrombosis (DVT). XALIA-LEA was conducted in regions not included in XALIA (Latin America, Eastern Europe, the Middle East, Africa, and the Asia-Pacific), and enrolled patients with isolated pulmonary embolism (PE).. Adult patients with acute venous thromboembolism (VTE) indicated for ≥3 months' anticoagulant treatment were eligible; treatment strategies were at the physician's discretion. Patients receiving rivaroxaban or standard anticoagulation (unfractionated or low-molecular weight heparin/fondaparinux alone or overlapping with and followed by a vitamin K antagonist [VKA]) were included in the safety analysis. "Early switchers" to rivaroxaban (i.e. after receiving heparin/fondaparinux for >2-14 days and/or a VKA for 1-14 days) were not included in the safety analysis set.. Of the 1972 eligible patients, 1285 received rivaroxaban, 402 received standard anticoagulation, and 285 were early switchers. Most patients who received rivaroxaban were appropriately selected, received the correct dosing schedule, reported few adverse effects. Outcomes were similar to previously published results, with rivaroxaban associated with a low rate of major bleeding (1.6%), recurrent VTE (1.4%) and all-cause mortality (2.3%). Including early switchers, relatively fewer patients with index isolated PE received rivaroxaban (14.4%) versus standard anticoagulation therapy (20.9%). Some regional variations and differences in outcomes by VTE subtype were apparent with standard anticoagulation treatment.. XALIA-LEA reaffirms the safety and effectiveness of rivaroxaban for VTE treatment for countries not included in XALIA.

Topics: Adult; Africa; Aged; Anticoagulants; Asia; Europe, Eastern; Factor Xa Inhibitors; Female; Humans; Latin America; Male; Middle Aged; Middle East; Prospective Studies; Rivaroxaban; Venous Thromboembolism; Vitamin K

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.

Topics: Acenocoumarol; Adult; Anticoagulants; Elasticity; Factor Xa Inhibitors; Female; Fibrin; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Viscosity; Vitamin K; Warfarin

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Topics: Aged; Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Propensity Score; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Survival Analysis; Treatment Outcome; Venous Thromboembolism

Cancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of major bleeding events were classified into four categories of increasing severity. A one-stage meta-analysis was used to evaluate the effect of cancer on the severity of the clinical presentation and course by estimating crude odds ratios (ORs) and ORs adjusted for age, sex and anticoagulant type with 95% confidence intervals (CIs). The study group comprised 290 patients with major bleeding, of whom 50 (17%) had cancer. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR, 0.90; 95% CI, 0.47-1.72). The clinical course was found to be severe in 20 and 25% of patients with and without cancer, respectively (adjusted OR, 0.75; 95% CI, 0.35-1.61). The present study suggests that the clinical presentation and course of anticoagulant-related major bleeding events are not more severe in cancer patients than in patients without cancer. This may be reassuring for physicians who treat cancer patients with anticoagulant-related bleeding.

Topics: Aged; Anticoagulants; Blood Transfusion; Double-Blind Method; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Prospective Studies; Pyridines; Rivaroxaban; Thiazoles; Venous Thromboembolism

Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge.. We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome).. A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43).. Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Double-Blind Method; Factor Xa Inhibitors; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Rivaroxaban; Venous Thromboembolism

The EINSTEIN-Extension trial (EINSTEIN-EXT) found that continued treatment with rivaroxaban for an additional 6 or 12 months (vs placebo) after 6-12 months of initial anticoagulation significantly reduced the risk of recurrent venous thromboembolism (VTE) with a small non-significant increased risk of major bleeding (none fatal or in critical site). This study aimed to compare total healthcare cost between rivaroxaban and placebo, based on the EINSTEIN-EXT event rates.. Total healthcare cost was calculated as the sum of treatment and clinical event costs from a US managed care perspective. Treatment duration and event rates were obtained from the EINSTEIN-EXT study. Adjustment on treatment duration was made by assuming a 10% non-adherence rate. Drug costs were based on wholesale acquisition costs. Cost estimates for clinical events (i.e. recurrent deep vein thrombosis [DVT], recurrent pulmonary embolism, major bleeding, clinically relevant non-major bleeding) were determined from the literature. Results were examined over a ±20% range of each cost component and over 95% confidence intervals (CIs) of event rate differences in deterministic (one-way) and probabilistic sensitivity analyses (PSA).. Total healthcare cost was $1,454 lower for rivaroxaban-treated (vs placebo-treated) patients in the base-case, with a lower clinical event cost fully offsetting drug cost. The cost savings of recurrent DVT alone (-$3,102) was greater than drug cost ($2,723). Total healthcare cost remained lower for rivaroxaban in the majority (73%) of PSA (cost difference [95% CI] = -$1,454 [-$2,396, $1,231]).. This study was conducted over the 1-year observation period of the EINSTEIN-EXT trial, which limited "real-world" applicability and examination of long-term economic impact. Assumptions on drug and clinical event costs were US-based and, thus, not applicable to other healthcare systems.. Total healthcare costs were estimated to be lower for patients continuing rivaroxaban therapy compared to those receiving placebo in VTE patients who had completed 6-12 months of VTE treatment.

Topics: Aged; Anticoagulants; Cost-Benefit Analysis; Double-Blind Method; Drug Administration Schedule; Female; Health Expenditures; Hemorrhage; Humans; Male; Middle Aged; Models, Econometric; Rivaroxaban; Time Factors; Venous Thromboembolism

The optimal duration of anticoagulation for venous thromboembolism (VTE) is uncertain. In this prespecified analysis, we used data from 2 randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with aspirin (100 mg) or placebo for extended VTE treatment to estimate the risk of recurrence according to baseline risk factor profiles. Index VTE events were centrally classified as unprovoked, or provoked by major transient or persistent, or minor transient or persistent risk factors, and rates of recurrence at 1 year were calculated. A total of 2832 patients received rivaroxaban; 1131 received aspirin, and 590 received placebo. With unprovoked VTE, rates of recurrence in the 1173 patients given rivaroxaban, the 468 given aspirin, and the 243 given placebo were 2.0%, 5.9%, and 10.0%, respectively. There were no recurrences in patients with VTE provoked by major transient risk factors. With VTE provoked by minor persistent risk factors, recurrence rates in the 1184 patients given rivaroxaban, the 466 given aspirin, and the 248 given placebo were 2.4%, 4.5%, and 10.7%, respectively. For patients with minor transient risk factors, recurrence rates were 0.4% in the 268 patients given rivaroxaban, 4.2% in the 121 given aspirin, and 7.1% in the 56 given placebo. Recurrence rates in patients with VTE provoked by minor persistent or minor transient risk factors were not significantly lower than that with unprovoked VTE (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.56-1.16; and HR, 0.68; 95% CI, 0.32-1.30, respectively). Therefore, such patients may also benefit from extended anticoagulation therapy.

Topics: Adult; Aged; Aspirin; Drug Administration Schedule; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Venous Thromboembolism

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Rivaroxaban; Survival Rate; Treatment Outcome; Venous Thromboembolism

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Double-Blind Method; Equivalence Trials as Topic; Female; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

Venous thromboembolism (VTE)-BLEED, a decision tool for predicting major bleeding during chronic anticoagulation for VTE has not yet been validated in practice-based conditions. We calculated the prognostic indices of VTE-BLEED for major bleeding after day 30 and day 90, as well as for recurrent VTE and all-cause mortality, in 4457 patients enrolled in the international, prospective XALIA study. The median at-risk time was 190 days (interquartile range 106-360). The crude hazard ratio (HR) for major bleeding after day 30 was 2·6 [95% confidence interval (CI) 1·3-5·2] and the treatment-adjusted HR was 2·3 (95% CI 1·1-4·5) for VTE-BLEED high (versus low) risk patients: the corresponding values for major bleeding after day 90 were 3·8 (95% CI 1·6-9·3) and 3·2 (95% CI 1·3-7·7), respectively. The predictive value of VTE-BLEED was similar in selected patients with unprovoked VTE or those treated with rivaroxaban. High VTE-BLEED score was associated with higher incidence of all-cause mortality (treatment-adjusted HR 11, 95% CI 4·8-23), but not evidently with recurrent VTE (treatment-adjusted HR 1·5; 95% CI 0·85-2·7). These results confirm the predictive value of VTE-BLEED in practice-based data in patients treated with rivaroxaban or conventional anticoagulation, supporting the hypothesis that VTE-BLEED may be useful for making management decisions on the duration of anticoagulant therapy.

Topics: Adult; Disease-Free Survival; Female; Hemorrhage; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Rivaroxaban; Survival Rate; Venous Thromboembolism; Young Adult

Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy.. In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding.. Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23).. Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .).

Topics: Aftercare; Aged; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Discharge; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Most international guidelines recommend pharmacological thromboprophylaxis after total hip and knee arthroplasty (THA/TKA) for 10 to 35 days. However, a recent cohort study on fast-track THA and TKA questioned the need for prolonged thromboprophylaxis when length of stay (LOS) is ≤ 5 days. We aimed at re-investigating the incidence of venous thromboembolism (VTE) in fast-track THA and TKA with in-hospital only thromboprophylaxis when LOS was ≤ 5 days. Prospective cohort study from 1 December 2011 to 30 October 2015 on elective unilateral THA/TKA with in-hospital only thromboprophylaxis if LOS was ≤ 5 days. Prospective information on co-morbidity and complete 90-day follow-up through the Danish National Patient Registry and medical records. Patients with pre-operative use of anticoagulants were excluded. In per protocol analysis, 17,582 (95.5%) had LOS of ≤ 5 days (median, 2 [interquartile range, 2-3]) and in-hospital thromboprophylaxis only. Incidence of symptomatic VTE was 0.40%, consisting of 28 (0.16%) pulmonary embolisms (PEs), 38 (0.22%) deep vein thrombosis (DVT) and 4 (0.02%) combined DVT and PE. Two PEs (0.01%) were fatal. VTE-associated risk factors with in-hospital only thromboprophylaxis were age > 85 years, odds ratio (OR) of 3.74 (95% confidence interval: 1.15-12.14,

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dalteparin; Denmark; Enoxaparin; Follow-Up Studies; Hospitals; Humans; Incidence; Middle Aged; Postoperative Complications; Prospective Studies; Risk; Rivaroxaban; Survival Analysis; Venous Thromboembolism

Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin.. In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding.. A total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups.. Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439 .).

Topics: Adult; Aged; Aspirin; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Rivaroxaban; Secondary Prevention; Venous Thromboembolism

Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio = 0.54, 95% confidence interval = 0.37-0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring.. To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective.. A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs.. Over a patient's lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds.. Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective.

Topics: Anticoagulants; Cost-Benefit Analysis; Female; Health Resources; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Markov Chains; Middle Aged; Models, Econometric; Netherlands; Quality-Adjusted Life Years; Rivaroxaban; Secondary Prevention; Venous Thromboembolism

The guidelines for the prevention of venous thromboembolism in orthopedic surgeries have reached a consensus on the postoperative conventional anticoagulation. However, the choice of anticoagulant drugs is yet controversial. The use of the drug rivaroxaban is expensive. Since the compliance of patients with low-molecular-weight heparin is considerably low, a cost-effective, efficacious and convenient anticoagulant program is essential. The present study investigated the efficacy, safety, patient compliance, and cost-effectiveness of low-molecular-weight heparin with sequential Rivaroxaban anticoagulant therapy in patients with a hip fracture, following internal fixation. A total of 287 patients with hip fractures were randomized into three groups: Rivaroxaban alone, Enoxaparin alone, and Enoxaparin followed by Rivaroxaban. The primary endpoint was the incidence of postoperative VTE, whereas the secondary endpoints were the compliance and treatment costs. Adverse reactions included bleeding and wound complications. The incidences of VTE were 5.21%, 14.74%, and 10.42% in the Rivaroxaban, low-molecular-weight heparin, and sequential therapy groups, respectively. The VTE-related mortality rates were 0%, 1.05%, and 1.04%. The average hospital stay was 12±8,15±7, and 11±5d, whereas the compliance rates of the three groups were 82.3%, 71.6%, and 88.5%, respectively. The incidences of adverse incisions were 14.6%, 4.2%, and 6.3% for the three groups examined. The effects and the incidence of postoperative bleeding in the treatment of low-molecular-weight heparin followed by Rivaroxaban did not differ significantly from that of Rivaroxaban alone. However, the postoperative drainage, the cost of treatment and the incidence of VTE reduced significantly, whereas the incidences of adverse incisions and the patient compliance were increased.. ChiCTR-INR-17010495.

Topics: Aged; Aged, 80 and over; China; Cost-Benefit Analysis; Double-Blind Method; Drug Administration Schedule; Drug Costs; Drug Therapy, Combination; Enoxaparin; Factor Xa Inhibitors; Female; Fracture Fixation, Internal; Hemorrhage; Hip Fractures; Humans; Male; Medication Adherence; Middle Aged; Prospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

Topics: Aspirin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Rivaroxaban; Secondary Prevention; Treatment Outcome; Venous Thromboembolism

Topics: Aspirin; Double-Blind Method; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Rivaroxaban; Venous Thromboembolism

Venous thromboembolism (VTE) is a frequent complication of cancer associated with morbidity, mortality, increased hospitalizations and higher health care costs. Cancer patients at increased risk for VTE can be identified using a validated risk assessment score, and the incidence of VTE can be reduced in high-risk settings using anticoagulation. Rivaroxaban is a potent, oral, direct, factor Xa inhibitor approved for the prevention and treatment of thromboembolic events, including VTE. CASSINI is a double-blind, randomized, parallel-group, multicentre study comparing rivaroxaban with placebo in adult ambulatory patients with various cancers who are initiating systemic cancer therapy and are at high risk of VTE (Khorana score ≥ 2). Patients with primary brain tumours or those at risk for bleeding are excluded. Approximately 700 patients will be randomized 1:1 to rivaroxaban 10 mg daily or placebo for up to 6 months if there is no evidence of VTE from compression ultrasonography (CU) during screening or from routine care imaging within 30 days prior to randomization. Mandatory CU will also be performed at weeks 8 and 16 (±7 days), and at study end (±3 days). The primary efficacy hypothesis is that anticoagulation with rivaroxaban reduces the composite of objectively confirmed symptomatic or asymptomatic, lower-extremity, proximal deep-vein thrombosis (DVT); symptomatic, upper-extremity DVT; symptomatic or incidental pulmonary embolism; and VTE-related death compared with placebo. The primary safety objective is to assess major bleeding events (Clinical trial information: NCT02555878).

Topics: Ambulatory Care; Blood Coagulation; Clinical Protocols; Double-Blind Method; Europe; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Neoplasms; North America; Pulmonary Embolism; Research Design; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Although many patients with venous thromboembolism (VTE) may need extended treatment, efficacy and safety issues of full- or lower-intensity anticoagulation over acetyl salicylic acid (ASA) treatment have remained to be determined. EINSTEIN CHOICE is a randomized, double-blind and phase 3 study, and compared either once-daily rivaroxaban (at doses of 20 mg or 10 mg) and 100 mg of ASA in patients with VTE who were in equipoise regarding the need for extended anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal VTE and the principal safety outcome was major bleeding. A total of 3365 patients were included in the intentionto-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 1.5% of patients receiving 20 mg of rivaroxaban and in 1.2% of patients receiving 10 mg of rivaroxaban, in comparison to 4.4% of those receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. ASA, 0.34; 95% confidence interval [CI] 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. ASA, 0.26; 95% CI 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding and adverse events were comparable among three treatment groups. In conclusion, in patients with VTE in equipoise for extended anticoagulation, either a treatment dose (20 mg) or a prophylactic dose (10 mg) of rivaroxaban compared with ASA significantly reduced the risk of VTE recurrence without a significant increase in bleeding risk.

Topics: Adult; Aged; Anticoagulants; Aspirin; Female; Humans; Male; Middle Aged; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Topics: Adult; Aged; Anticoagulants; Canada; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Medication Therapy Management; Middle Aged; Outcome and Process Assessment, Health Care; Patient Readmission; Risk Assessment; Rivaroxaban; United States; Venous Thromboembolism; Warfarin

Multiple randomized controlled trials have documented the effectiveness of rivaroxaban in the prevention of venous thromboembolism up to 1-month following total joint arthroplasty. However, the effectiveness and safety of rivaroxaban in the real-world setting, outside of the strict protocols used by randomized clinical trials, are unknown.. This was a prospective, observational, noninterventional, phase IV study of 3914 consecutive patients who underwent total joint arthroplasty from June 2010 to December 2012. Patients were treated with rivaroxaban 10 mg by mouth daily starting postoperative day 1 and continued for 15 days. Participants were followed up in clinic at 6 weeks and contacted by telephone at 12 weeks. The primary outcome of interest was symptomatic venous thromboembolism; secondary outcomes included bleeding events, transfusion requirements, and death.. The incidence of symptomatic deep venous thrombosis at 3 months was 0.5% (n = 18). Only 1 deep venous thrombosis event occurred within 7 days of surgery. The incidence of symptomatic pulmonary embolism (PE) at 3 months was 0.7% (n = 28). Thirteen PEs (46%) occurred within 7 days of surgery. The rate of major bleeding while on prophylaxis was 0.1%. Only 5% of patients received a blood transfusion. No deaths were attributed to thromboembolic events.. This prospective, observational, phase IV study demonstrates that rivaroxaban appears to protect patients against symptomatic PE and is not associated with major bleeding events when used in a real-world setting as described.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Young Adult

The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared rivaroxaban and apixaban with conventional anticoagulation therapy for acute venous thromboembolism (VTE), respectively, are often compared. However, the trials differed in duration of therapy (3-12 and 6months, respectively) and in patient selection (few exclusion criteria and more stringent exclusion criteria, respectively).. To determine the effect of these methodological differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY and were treated for at least 6months (cohort 1) and the 2368 patients who would have been ineligible for AMPLIFY (cohort 2).. Compared with patients in cohort 2, those in cohort 1 were older and more often male and there were more with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1, rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR], 0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95% CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2.. This analysis illustrates the influence of patient selection and treatments duration on outcome results and highlights the limitations of cross-trial comparisons.

Topics: Adult; Aged; Cohort Studies; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Selection; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery. Studies of direct oral anticoagulants (DOACs) are not available in this surgical field. The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic (PK/PD) parameters of rivaroxaban in bariatric patients.. In this single-centre study, obese patients received single oral doses of rivaroxaban (10 mg) 1 day prior to and 3 days after bariatric surgery. PK and PD parameters were assessed at baseline and during 24 h after drug ingestion.. Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study. Mean rivaroxaban area under plasma concentration-time curve, peak plasma concentration, time to peak plasma concentration and terminal half-life were 971.9 μg·h l. Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in PD.

Topics: Administration, Oral; Adult; Antithrombins; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Gastric Bypass; Half-Life; Humans; Male; Middle Aged; Obesity; Postoperative Complications; Postoperative Period; Preoperative Period; Prothrombin; Rivaroxaban; Thrombin; Venous Thromboembolism

BACKGROUND This study aimed to assess whether the efficacy of tranexamic acid (TXA) would be altered when rivaroxaban or enoxaparin was used for thromboprophylaxis in primary total knee replacement (TKR). It was hypothesized that the hemostatic effect of TXA would be better with the use of enoxaparin. MATERIAL AND METHODS A randomized clinical trial was conducted on 194 patients undergoing primary TKR for osteoarthritis. An intravenous dose of 15 mg/kg (TXA) and 1 g topical TXA were used. Patients randomly received enoxaparin or rivaroxaban prophylaxis when the drainage was less than 30 ml/h 6-8 h postoperatively. The primary endpoint was hidden blood loss (HBL). Indexes of total blood loss drainage, hemoglobin drop, transfusion, range of motion (ROM), HSS score, VAS pain score, knee swelling, length of hospital stay (LOHS), incidence of venous thromboembolism, major/minor bleeding, and wound complications were also compared between the groups. RESULTS More than 80% of patients initiated anticoagulation within 6 h postoperatively. No statistically significance difference was detected in terms of HBL (679.0±205.6 vs. 770.5±206.1, p=.062) or other bleeding index, ROM, or LOHS. The motion VAS pain score and knee swelling (16.7% vs. 6.1%, p=.021) were significantly lower, and HSS score at discharge was higher in the enoxaparin group. The rivaroxaban group had less asymptomatic deep venous (4.1% vs. 0%, p=.121) and muscular venous thrombosis (2.1% vs. 9.2%, p=.033); more ecchymosis (13.5% vs. 10.2%, p=.472), and wound complications (13.5% vs. 6.1%, p=.082). No episodes of transfusion, pulmonary embolism, or major bleeding occurred in either group. CONCLUSIONS More attention should be paid to the increased risk of wound complications and knee swelling associated with rivaroxaban, although the hidden blood loss was similar in both groups.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Coagulation; Drug Interactions; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Osteoarthritis; Pilot Projects; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Tranexamic Acid; Venous Thromboembolism

Acute venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is traditionally managed with a short course of parenteral anticoagulation followed by 3-6 months of a vitamin-K antagonist. Non-vitamin K oral anticoagulants (NOACs) do not require routine monitoring and dose adjustment, thus potentially provide an alternative treatment option.. Because of the lack of head-to-head clinical studies, an indirect comparison was conducted of dabigatran etexilate and rivaroxaban based on the respective phase III clinical trial. The derived relative safety and efficacy estimates were used to evaluate the cost-utility of dabigatran compared with rivaroxaban in the treatment and secondary prevention of VTE. The results of the indirect comparison showed no significant difference between dabigatran and rivaroxaban in avoiding recurrent VTE following index PE, index DVT, or DVT/PE combined, in treatment and extended anticoagulation. Dabigatran has significantly less major or clinically relevant bleeds (MCRBE) compared to rivaroxaban in treatment after index DVT and treatment after DVT or PE combined, but was not significantly different from rivaroxaban after index PE or in extended anticoagulation. In cost-utility deterministic analyses, dabigatran was projected dominant in all analyzed settings, given its marginally lower total cost and marginally higher QALYs gained compared to rivaroxaban. Probabilistic analyses results showed a high likelihood of dabigatran being considered good value for money in the UK, in treatment and in secondary prevention of VTE.. The cost-effectiveness evaluations showed that dabigatran can be considered the dominant treatment strategy compared to rivaroxaban in the patients' sub-groups considered, given the projected marginally higher clinical benefits and lower treatment costs.

Topics: Anticoagulants; Cost-Benefit Analysis; Dabigatran; Double-Blind Method; Female; Health Services; Hemorrhage; Humans; Male; Middle Aged; Models, Econometric; Pulmonary Embolism; Quality-Adjusted Life Years; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

The study aim was to identify predictive factors for major bleeding in patients receiving the novel oral factor Xa inhibitor rivaroxaban or enoxaparin-vitamin K antagonists (VKAs) for the treatment of acute symptomatic venous thromboembolism. We analysed data from patients included in the phase III EINSTEIN DVT and EINSTEIN PE studies. Factors associated with major bleeding events were assessed with best subset variable selection using Cox proportional hazards regression model. Three time windows were considered, i.e. the initial three weeks, after the third week onwards, and the entire duration of the anticoagulant treatment. Model discrimination was estimated using the C-statistic and validated internally by bootstrap techniques. Major bleeding occurred in 40 (1.0%) of 4130 patients receiving rivaroxaban and in 72 (1.7%) of 4116 receiving enoxaparin/VKAs, with 44% of the major bleeding events occurring in the first three weeks of treatment. Significant risk factors for major bleeding were older age, black race, low haemoglobin concentrations, active cancer, and antiplatelet or non-steroidal anti-inflammatory drug therapy. The discrimination of the model for major bleeding was high for the first three weeks (C-statistic 0.73), from the fourth week onwards (C-statistic 0.68), and the entire period of anticoagulant treatment (C-statistic 0.74). This analysis identified risk factors for major bleeding in patients receiving the novel oral anticoagulant rivaroxaban or enoxaparin/VKAs for the treatment of acute venous thromboembolism. The prognostic model based on the combination of identified risk factors may be informative to estimate the risk of major bleeding both during the initial and later phases of anticoagulation.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Black or African American; Blood Coagulation; Data Interpretation, Statistical; Enoxaparin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemoglobins; Hemorrhage; Heparin; Humans; Male; Middle Aged; Neoplasms; Platelet Aggregation Inhibitors; Prognosis; Proportional Hazards Models; Regression Analysis; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

The aim of the present study was to analyse concomitant drug use and its association with outcome in patients (N = 17 701) receiving rivaroxaban or standard of care (SOC) for the prevention of venous thromboembolism after major orthopaedic surgery in the non-interventional, phase IV XAMOS (Xarelto® in the prophylaxis of post-surgical venous thromboembolism after elective major orthopaedic surgery of hip or knee) study.. Concomitant drug use was at the discretion of the treating physician. Prespecified co-medications of interest were cytochrome P450 (CYP) 3A4/P-glycoprotein inhibitors/inducers, platelet aggregation inhibitors (PAIs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Crude event incidences were compared between rivaroxaban and SOC groups.. CYP3A4/P-glycoprotein inhibitor/inducer use was infrequent, in contrast to PAI (~7%) and NSAID (~52%) use. Rivaroxaban was associated with a lower incidence of overall symptomatic thromboembolic events compared with SOC, regardless of co-medication use. In both treatment groups, PAI users, with higher age and prevalence of cardiovascular co-morbidities, had similar higher (>7-fold) incidences of symptomatic arterial but not venous thromboembolic events compared with non-users. NSAID use had no influence on thromboembolic events. However, odds ratios (ORs) for major bleeding events (European Medicines Agency definition) were higher in NSAID users compared with non-users in rivaroxaban [OR = 1.50; 95% confidence interval (CI) 1.06, 2.13] and SOC (OR = 1.70; CI 1.16, 2.49) groups. In PAI users, ORs for major bleeding events were no different from those of non-users in both the rivaroxaban (OR = 1.49; CI 0.84, 2.65) and SOC (OR = 1.46; CI 0.82, 2.62) groups.. Use of NSAIDs in XAMOS was frequent and associated with a higher frequency of bleeding events in patients receiving rivaroxaban or SOC, although the benefit-risk profile of rivaroxaban compared with SOC was maintained.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cohort Studies; Drug Interactions; Female; Hemorrhage; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism

Rivaroxaban is a target-specific oral anticoagulant approved for the treatment of venous thromboembolism (VTE). On its major clinical trials, treatment was initiated directly with a 3-week dose of oral 15 mg twice daily followed by 20 mg every day for at least 3 months. We retrospectively evaluated an initial therapy for confirmed VTE with 1 to 18 days of enoxaparin (1 mg/kg twice daily parenteral) followed by oral rivaroxaban 20 mg every day. Of 49 patients, we found no symptomatic recurrence, no major bleeding, and only 1 clinically relevant nonmajor bleeding. We concluded in this pilot study that it is safe and effective to treat patients with enoxaparin course followed directly by a dose of 20 mg of rivaroxaban.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Enoxaparin; Female; Humans; Lower Extremity; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism

This prospective study was conducted to report the effect of oral factor Xa inhibitor and low-molecular-weight heparin (LMWH) on surgical complications following total hip arthroplasty (THA). The patients with an age < 60 years were randomly assigned to three groups (rivaroxaban, enoxaparin, and placebo) and the patients with an age ≥ 60 years were assigned to two groups (rivaroxaban and enoxaparin). All drug regimens started at 12 hours postoperatively and continued for two weeks after surgery. Primary measure outcome was major surgical wound complications defined as haematoma requiring any intervention, superficial wound infection, deep periprosthetic infection, and increased wound bleeding. Secondary measured outcome included minor surgical complications (swelling, drainage, erythema, and oozing), organ bleeding, and venous thromboembolic (VTE) events. A total of 184 patients aged < 60 years and 167 patients aged ≥ 60 years were included as the analysis population per group. Up to 14 days after surgery, the overall incidence of major surgical complications associated with thromboprophylaxis was 6.5 % (58/886). There were no significant differences in the rate of major surgical complications among all the three groups of the patients aged < 60 years and between two groups of the patients aged ≥ 60 years. For the patients aged < 60 years, wound oozing continued significantly longer in the pharmacological group than in the placebo group, but wound infection did not occur in any case. The VTE events were similar in all the groups.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Placebos; Postoperative Complications; Postoperative Period; Prospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Wound Healing

Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.

Topics: Adult; Aged; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Discharge; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Time Factors; Venous Thromboembolism

Major orthopaedic surgery is associated with an increased risk of venous thromboembolism. Direct oral anticoagulants (DOACs) are recommended as thromboprophylactic agents after orthopaedic surgery. Although routine monitoring of DOACs in general is not required, measuring DOAC concentration may be necessary in clinical settings. The effects of DOACs on routine coagulation assays in spiked material are studied extensively, however, few data are available on DOAC concentration in patients after major orthopaedic surgery. We measured trough and peak DOAC concentrations with UPLC-MS/MS and routine coagulation tests in a prospective study including 40 patients receiving thromboprophylactic treatment with dabigatran 220mg od and 40 patients receiving rivaroxaban 10mg od after major orthopaedic surgery. For rivaroxaban, the median trough concentration with UPLC-MS/MS was 17.1ng/mL and median peak concentration was 149ng/mL. The anti-Xa assay displayed a good correlation, but a positive bias in comparison to the reference method. Furthermore, trough levels were mostly below the LOD of the anti-Xa assay. For dabigatran, the median trough concentration with UPLC-MS/MS was 12.1ng/mL, and median peak level was 80.8ng/mL. A positive bias was found when results from coagulation assays were compared to UPLC-MS/MS data. However, the addition of glucuronidated metabolites to dabigatran concentration UPLC-MS/MS data generally resolved most of this bias. Age was found to have a significant influence on dabigatran pharmacokinetics, irrespective of kidney function, whereas no effect of age was found during rivaroxaban treatment. In both treatment groups, female subjects displayed faster pharmacokinetics in comparison to male subjects, although not reaching significance. We conclude that UPLC-MS/MS is the method of choice to measure trough concentrations of DOACs in patients after orthopaedic surgery. Current coagulation assays are not suited for this purpose. We found large heterogeneity in both peak and trough concentrations of DOACs, and showed that pharmacokinetics of novel oral anticoagulants may be influenced by age and gender. Whether patients with high or low trough concentrations are at increased risk for bleeding or thromboembolic events respectively remains to be established.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Chromatography, High Pressure Liquid; Dabigatran; Drug Monitoring; Female; Humans; Male; Middle Aged; Orthopedic Procedures; Rivaroxaban; Tandem Mass Spectrometry; Venous Thromboembolism

Patients with superficial vein thrombosis (SVT) are commonly treated with low-molecular weight heparin or fondaparinux in prophylactic, intermediate or therapeutic dosages for treatment periods of 10-45 days. This practice is also reflected by the current guideline recommendations. However, given the broad range of thromboembolic complication rates in SVT (between 0 and 30 % have been reported) it seems reasonable to suspect that risk stratification is needed to differentiate patients at low risk who may not benefit from anticoagulation from those at high risk who may need higher dosages or a longer duration of anticoagulation. Furthermore, prolonged treatment with injectable anticoagulants has been shown to result in poor patient adherence. Direct oral anticoagulants have recently been approved for venous thromboembolism therapy and these new drugs may offer advantages also for SVT patients. The prospective, randomized, open-label, blinded adjudication trial superficial phlebitis treated for 45 days with rivaroxaban versus fondaparinux (SURPRISE) will evaluate the efficacy and safety of 10 mg rivaroxaban OD compared to fondaparinux 2.5 mg OD for SVT treatment in a subset of high-risk SVT patients over a treatment period of 45 days. The purpose of the study is to demonstrate non-inferiority of rivaroxaban compared to fondaparinux in preventing the combined efficacy endpoint of thrombus progression, SVT recurrence, DVT, PE and death. The results of the SURPRISE trial will provide evidence for the concept of risk stratification in SVT and for the value of rivaroxaban 10 mg in SVT treatment (clinicaltrials.gov NCT01499953).

Topics: Disease Progression; Fondaparinux; Humans; Polysaccharides; Recurrence; Risk Assessment; Rivaroxaban; Single-Blind Method; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8 % vs 6.1 %, respectively, p=0.03; absolute risk difference, -5.3 %, 95 % CI, -11.4 to -0.8; crude relative risk 0.14, 95 % CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected "high-risk" subjects, remains to be determined. A larger trial to verify our preliminary results is warranted.

Topics: Adult; Anterior Cruciate Ligament Reconstruction; Arthroscopy; Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Knee Joint; Male; Meniscectomy; Middle Aged; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Short-term anticoagulant treatment for acute DVT or pulmonary embolism (PE) effectively reduces the risk of recurrent disease during the first 6 to 12 months of therapy. Continued anticoagulation often is not instituted because of the perception among physicians that the risk of major bleeding will outweigh the risk of new venous thrombotic episodes.. The authors performed a benefit-risk analysis by using the randomized EINSTEIN-Extension trial, which compared continued rivaroxaban with placebo in 1,197 patients with symptomatic DVT or PE who had completed 6 to 12 months of anticoagulation and in whom physicians had equipoise with respect to the need for continued anticoagulation. One-year Kaplan-Meier rates and rate differences of recurrent VTE and major bleeding were calculated. Benefits and risks were assessed using rate differences scaled to a population size of 10,000 patients treated for 1 year.. Recurrent VTE occurred in eight recipients of rivaroxaban and 42 patients receiving placebo. In a population of 10,000 patients treated for 1 year, rivaroxaban treatment would have resulted in 665 (95% CI, 246-1,084) fewer recurrent VTEs than would placebo (number needed to treat = 15). Major bleeding occurred in four (0.7%) and zero patients, respectively. Rivaroxaban treatment would have resulted in 68 (95% CI, 2-134) more major bleeding events than would placebo (number needed to harm = 147). Kaplan-Meier analysis showed early recurrent VTE reduction with rivaroxaban that continued to improve throughout treatment; major bleeding increased gradually, plateauing at approximately 100 days.. A clinically important benefit and a favorable benefit-risk profile of continued rivaroxaban anticoagulation was observed.. ClinicalTrials.gov; No.: NCT00439725; URL: www.clinicaltrials.gov.

Topics: Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Survival Rate; Treatment Outcome; Venous Thromboembolism

Real-world data on the use of rivaroxaban in the perioperative period in patients undergoing major orthopedic surgery are limited. Subsets of data from the Phase IV, non-interventional XAMOS study were analyzed to explore the potential influence of timing of the first thrombo prophylactic dose, type of anesthesia, and concomitant mechanical prophylaxis on clinical outcomes in patients undergoing major orthopedic surgery in routine clinical practice.. In XAMOS, 8,778 patients received rivaroxaban (10 mg once daily) and 8,635 received standard-of-care (SOC) pharmacological prophylaxis (safety population). Crude incidences of symptomatic thromboembolic and treatment-emergent bleeding events were analyzed according to timing of the first postoperative thromboprophylactic dose, use of general or neuraxial anesthesia, and use of mechanical prophylaxis with pharmacological thromboprophylaxis.. In the rivaroxaban group, the incidences of symptomatic thromboembolic events were 0.7%, 1.0%, and 0.7% in patients receiving the first thromboprophylactic dose at ≤6 hours, >6 hours to ≤10 hours, and >10 hours to ≤24 hours after surgery, respectively. In the SOC group, the incidence of symptomatic thromboembolic events was slightly higher when the postoperative dose was given at >10 hours to ≤24 hours (1.8% vs 1.1% at ≤6 hours and 1.3% at >6 hours to ≤10 hours). The antithrombotic effect of rivaroxaban was maintained in comparison to the SOC group. The incidence of major bleeding (RECORD trial definition) was low and similar between the two treatment groups and was not influenced by timing of the first thromboprophylactic dose. Neuraxial anesthesia was used more than any other form of anesthesia for both hip and knee surgery; the effectiveness of rivaroxaban was not influenced by the type of anesthesia used. No spinal hematomas were reported in patients receiving neuraxial anesthesia in either treatment group. Use of mechanical thromboprophylaxis in addition to rivaroxaban or SOC pharmacological prophylaxis did not reduce the risk of thromboembolic events further.. The effectiveness and safety of rivaroxaban in patients undergoing major orthopedic surgery in routine clinical practice were maintained irrespective of timing of the first postoperative dose within 24 hours after surgery, the type of anesthesia, and the additional use of mechanical thromboprophylaxis.

Topics: Anesthesia, Conduction; Anesthesia, General; Blood Coagulation; Drug Administration Schedule; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Incidence; Orthopedic Procedures; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

The pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deep-vein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox proportional hazards model. Analyses were performed for both the first 21 days of treatment and the whole treatment period. For rivaroxaban recipients, there was no association between bodyweight or body mass index (BMI) and risk of recurrent VTE (ptrend=0.87 and 0.62, respectively), major bleeding (ptrend=0.24 and 0.36, respectively) or clinically relevant bleeding (ptrend=0.17 and 0.63, respectively). Major bleeding events were numerically lower in rivaroxaban patients across all bodyweight and BMI categories. Hazard ratios for rivaroxaban vs enoxaparin/VKA were similar in all bodyweight and BMI categories, both during the first 21 days and the whole treatment period. The fixed-dose rivaroxaban regimen is not associated with an increased risk of major bleeding or recurrent VTE in patients with either a low or high bodyweight. A high BMI was not associated with an increased risk of recurrent VTE during anticoagulation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Enoxaparin; Female; Humans; Male; Middle Aged; Recurrence; Rivaroxaban; Venous Thromboembolism; Vitamin K; Young Adult

Traditionally, patients with pulmonary embolism (PE) are admitted from the emergency department and treated with low-molecular-weight heparin followed by warfarin. Several studies now demonstrate that it is possible to identify low-risk PE patients that can safely be treated as outpatients. The advent of the direct-acting oral anticoagulants such as rivaroxaban has made it easier than ever to manage patients outside of the hospital. This article describes the design of a randomized controlled trial aimed at testing the hypothesis that low-risk PE patients can be safely and effectively managed at home using rivaroxaban, resulting in fewer days of hospitalization than standard-of-care treatment.. We have initiated a multicenter, open-label, randomized clinical trial in which low-risk adult PE patients (identified by the Hestia criteria) are randomized to outpatient management with oral rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily for 90 days versus standard care, determined by the treating physician and based on local practices. The primary clinical endpoint will be the total number of inpatient hospital days (including the index admission) for venous thromboembolic or bleeding-related events during the first 30 days after randomization. A total of 150 subjects per group will provide 82% power to detect a difference of 1 day or greater in the primary outcome.. Patient enrollment is ongoing at present in 45 of 60 planned sites. No interim analysis is planned and the study is being monitored by a data safety management board.. The MERCURY PE study is designed to test the hypothesis that outpatient management of low-risk PE patients with rivaroxaban reduces the number of hospitalization days from venous thromboembolism and bleeding compared with standard care. This article describes the rationale and methodology for this study.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Hospitalization; Humans; Pulmonary Embolism; Research Design; Rivaroxaban; Venous Thromboembolism

In the EINSTEIN DVT and EINSTEIN PE studies, the majority of patients received heparins to bridge the period during venous thromboembolism (VTE) diagnosis confirmation and the start of the study. In contrast to vitamin K antagonists (VKAs), rivaroxaban may not require initial heparin treatment.. To evaluate the effect of prestudy heparin on the efficacy and safety of rivaroxaban relative to enoxaparin/VKA, the 3-month incidence of recurrent VTE, and the 14-day incidence of major and nonmajor clinically relevant bleeding were compared in patients who did and did not receive prestudy heparin.. Of the 8,281 patients randomized, 6,937 (83.8%) received prestudy heparin (mean ± SD duration = rivaroxaban: 1.04 [± 0.74] days; enoxaparin 1.03 [± 0.42] days), and 1,344 (16.2%) did not. In patients who did not receive prestudy heparin, the incidences of recurrent VTE were similar in rivaroxaban (15 of 649, 2.3%) and enoxaparin/VKA (13 of 695, 1.9%) patients (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 0.52 to 2.37). The incidences of recurrent VTE were also similar in rivaroxaban (54 of 3,501, 1.5%) and enoxaparin/VKA (69 of 3,436, 2.0%) patients who did receive prestudy heparin (adjusted HR = 0.74; 95% CI = 0.52 to 1.06; pinteraction  = 0.32). The incidences of major or nonmajor clinically relevant bleeding with rivaroxaban were not significantly different from those with enoxaparin/VKA, either with (105 of 3,485, 3.0% vs. 104 of 3,428, 3.0%; adjusted HR = 0.98; 95% CI = 0.75 to 1.29) or without (24 of 645, 3.7% vs. 30 of 688, 4.4%; adjusted HR = 0.81; 95% CI = 0.46 to 1.40; pinteraction  = 0.68) prestudy heparin.. Although the majority of patients in the EINSTEIN studies received prestudy heparin, there were no notable differences in treatment effect of rivaroxaban versus enoxaparin/VKA in those who did and did not receive it.

Topics: Adult; Aged; Anticoagulants; Enoxaparin; Female; Hemorrhage; Heparin; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Safety; Thiophenes; Venous Thromboembolism; Vitamin K

In Japan, the standard of care for the treatment of pulmonary embolism (PE) and/or deep vein thrombosis (DVT) consists of intravenous unfractionated heparin (UFH) followed by warfarin, which was recently compared with rivaroxaban, an oral factor Xa inhibitor, in randomized trials.. To examine the length of hospital stay in patients with PE and/or DVT receiving rivaroxaban compared to Japanese standard therapy in the Japanese (J)-EINSTEIN PE and DVT program.. Open-label, randomized clinical trials that compared 3, 6, or 12 months of rivaroxaban with UFH and warfarin in patients with acute, confirmed symptomatic proximal PE and/or DVT. Decisions regarding hospital admission and/or discharge were left to the clinical judgment of attending physicians. Analyses were conducted in the intention-to-treat (ITT) population.. In the ITT population (N = 97), overall patient characteristics were similar in both treatment arms. The median length of stay in rivaroxaban patients was 10.0 days (interquartile range [IQR] 6.0 to 15.0 days) while it was 15.0 days (IQR 9.0 to 22.0) for patients on standard therapy (p = 0.016). All of the four DVT patients who were not hospitalized for the index event were in the rivaroxaban arm.. Our results suggest that treatment with rivaroxaban may significantly reduce the length of hospital stay in patients hospitalized for PE and/or DVT compared with the current standard of care in Japan, thereby reducing the burden on patients and the healthcare system. The limitations of our study include small sample size and the generalizability of the findings to the real-world setting. Further research is warranted to identify PE and/or DVT patients in Japanese clinical practice who may potentially be managed as outpatients.. Clinicaltrials.gov: NCT01516814 and NCT01516840.

Topics: Aged; Aged, 80 and over; Anticoagulants; Asian People; Female; Heparin; Humans; Japan; Length of Stay; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; 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

Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

Topics: Aspirin; Clinical Protocols; Double-Blind Method; Drug Administration Schedule; Fibrinolytic Agents; Hemorrhage; Humans; Recurrence; Research Design; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for preventing venous thromboembolism (VTE) after lumbar spine surgery.. In this randomized, controlled study, 665 patients who underwent lumbar surgery were randomly assigned to receive either rivaroxaban or parnaparin. Rivaroxaban and parnaparin were used for preventing postoperative venous thrombosis. The occurrence of postoperative efficacy endpoint events (venous thrombosis) and safety endpoint events (hemorrhage) was compared for each group.. Efficacy endpoint results: in the rivaroxaban group, there were 6 thrombotic events (1.7%), 2 cases with severe VTE (0.6%), and 3 cases with symptomatic VTE (0.9%). In the parnaparin group, there were 10 thrombotic events (3.1%), 4 cases with severe VTE (1.2%), and 6 cases with symptomatic VTE (1.9%). Safety endpoint results: in the rivaroxaban group, there were 21 cases with bleeding events (6.2%), 2 cases with severe bleeding (0.6%), and 19 cases with non-severe bleeding (5.6%). In the parnaparin group, there were 21 bleeding events (6.2%), 1 case with severe bleeding (0.3%), and 16 cases with non-severe bleeding (4.9%). The incidences of thromboembolic events, including severe and symptomatic VTE, were not significantly different between the two groups (P > 0.05). Bleeding event rates, including severe and non-severe bleeding, were also not significantly different.. Rivaroxaban proved to be equally effective as parnaparin for anticoagulation therapy, with both drugs exhibiting a similar prevention effect against postoperative VTE after lumbar spine surgery, without increasing the risk of postoperative bleeding.

Topics: Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Lumbar Vertebrae; Middle Aged; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Topics: Acute Disease; Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morpholines; Patient Satisfaction; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Rivaroxaban demonstrated superior efficacy and a similar safety profile to enoxaparin for the prevention of venous thromboembolism in the phase III RECORD programme in patients undergoing elective hip or knee replacement surgery. The XAMOS study investigated adverse events, including bleeding and thromboembolic events, in patients receiving rivaroxaban for thromboprophylaxis in routine clinical practice. XAMOS was a non-interventional, open-label cohort study in patients undergoing major orthopaedic surgery of the hip or knee (predominantly elective arthroplasty), in which rivaroxaban was compared with other pharmacological thromboprophylaxis. All adverse events were documented, including symptomatic thromboembolic and bleeding events. Crude and adjusted incidences based on propensity score subclasses were calculated and compared between the rivaroxaban and standard-of-care groups. A total of 17,701 patients were enrolled from 252 centres in 37 countries. Crude incidences of symptomatic thromboembolic events three months after surgery in the safety population were 0.89% in the rivaroxaban group (n=8,778) and 1.35% in the standard-of-care group (n=8,635; odds ratio [OR] 0.65; 95% confidence interval [CI] 0.49-0.87), and 0.91% and 1.31% (weighted) in the propensity score-adjusted analysis (OR 0.69; 95% CI 0.56-0.85), respectively. Treatment-emergent major bleeding events (as defined in the RECORD studies) occurred in 0.40% and 0.34% of patients in the rivaroxaban and standard-of-care groups in the safety population (OR 1.19; 95% CI 0.73-1.95), and in 0.44% versus 0.33% (weighted) in the propensity score-adjusted analysis (OR 1.35; 95% CI 0.94-1.93), respectively.This study in unselected patients confirmed the favourable benefit-risk profile of rivaroxaban seen in the RECORD programme.

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cohort Studies; Data Interpretation, Statistical; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Odds Ratio; Propensity Score; Risk; Rivaroxaban; Standard of Care; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Knowledge of anticoagulation status during rivaroxaban therapy is desirable in certain clinical situations. It was the study objective to determine coagulation tests most useful for assessing rivaroxaban's anticoagulant effect. Peak and trough blood samples from 29 patients taking rivaroxaban 20 mg daily were collected. Mass spectrometry and various coagulation assays were performed. "On-therapy range" was defined as the rivaroxaban concentrations determined by LC-MS/MS. A "misprediction percentage" was calculated based on how often results of each coagulation assay were in the normal reference range, while the rivaroxaban concentration was in the "on-therapy" range. The on-therapy range was 8.9-660 ng/ml. The misprediction percentages for prothrombin time (PT) and activated partial thromboplastin time (aPTT), using multiple reagents and coagulometers, ranged from 10%-52% and 31%-59%, respectively. PT, aPTT and activated clotting time (ACT) were insensitive to trough rivaroxaban: 59%, 62%, and 80% of samples had a normal result, respectively. Over 95% of PT and ACT values were elevated at peak. Four different rivaroxaban calibrated anti-Xa assays had R² values >0.98, demonstrating strong correlations with rivaroxaban drug levels. In conclusion, PT, aPTT and ACT are often normal in patients on therapeutic doses of rivaroxaban. However, PT and ACT may have clinical utility at higher drug plasma levels. Rivaroxaban calibrated anti-factor Xa assays can accurately identify low and high on-therapy rivaroxaban drug levels and, therefore, have superior utility in all clinical situations where assessment of anticoagulation status may be beneficial.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Cross-Sectional Studies; Factor Xa; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Partial Thromboplastin Time; Point-of-Care Systems; Prothrombin Time; Reference Values; Rivaroxaban; Thiophenes; Venous Thromboembolism; Whole Blood Coagulation Time

Thromboprophylaxis with rivaroxaban has proved effective and safe in patients undergoing hip and knee replacement surgery. As it is unclear whether it is also effective and safe in fracture patients, the aim of the present study was to evaluate the efficacy and safety of rivaroxaban in patients with lower limb fractures. We performed a retrospective cohort study of 2,050 consecutive patients treated for lower limb fractures at our trauma center, comparing rates of venous thromboembolism (VTE), bleeding and surgical complications, and the length of hospital stay for 608 patients who received rivaroxaban and 717 who received a low-molecular-weight heparin (LMWH). Rates of symptomatic VTE were 4.9 and 8.6% in the rivaroxaban and LMWH groups, respectively (p = 0.008), and distal VTE rates were 1.8 and 5.7%, respectively (p = 0.036). The incidence of major bleeding events in the rivaroxaban group was also lower than in the LMWH group (0.2 vs 0.6%), but the difference between the groups was not statistically significant. The mean length of hospital stay was significantly shorter in the rivaroxaban group (12.2 vs 13.1 days, respectively; p = 0.016). This retrospective cohort study is the first report documenting the efficacy and safety of rivaroxaban in patients with lower extremity fractures. In comparison with LMWH, rivaroxaban reduced the incidence of VTE by 45% without increasing the risk of bleeding. However, prospective, randomized controlled trials comparing rivaroxaban and LMWH are needed to confirm our findings.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Fractures, Bone; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Length of Stay; Lower Extremity; Male; Middle Aged; Morpholines; Postoperative Complications; Retrospective Studies; Rivaroxaban; Thiophenes; Venous Thromboembolism

D-dimer concentrations have not been evaluated extensively as a predictor of increased venous thromboembolism (VTE) risk in acutely ill, hospitalized medical patients.. To analyze the relationships between D-dimer concentration, VTE and bleeding in the MAGELLAN trial (NCT00571649).. This was a multicenter, randomized, controlled trial. Patients aged ≥ 40 years, hospitalized for acute medical illnesses with risk factors for VTE received subcutaneous enoxaparin 40 mg once daily for 10 ± 4 days then placebo up to day 35, or oral rivaroxaban 10 mg once daily for 35 ± 4 days. Patients (n = 7581) were grouped by baseline D-dimer ≤ 2 × or > 2 × the upper limit of normal. VTE and major plus non-major clinically relevant bleeding were recorded at day 10, day 35, and between days 11 and 35.. The frequency of VTE was 3.5-fold greater in patients with high D-dimer concentrations. Multivariate analysis showed that D-dimer was an independent predictor of the risk of VTE (odds ratio 2.29 [95% confidence interval 1.75-2.98]), and had a similar association to established risk factors for VTE, for example cancer and advanced age. In the high D-dimer group, rivaroxaban was non-inferior to enoxaparin at day 10 and, unlike the low D-dimer group, superior to placebo at day 35 (P < 0.001) and days 11-35 (P < 0.001). In both groups, bleeding outcomes favored enoxaparin/placebo.. Elevated baseline D-dimer concentrations may identify acutely ill, hospitalized medical patients at high risk of VTE for whom extended anticoagulant prophylaxis may provide greater benefit than for those with low D-dimer concentrations.

Topics: Acute Disease; Adult; Aged; Anticoagulants; Enoxaparin; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Morpholines; Multivariate Analysis; Risk Factors; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Whether heart failure (HF) increases the risk of venous thromboembolism (VTE) is not well established. In the phase III MAGELLAN (Multicenter, rAndomized, parallel Group Efficacy and safety study for the prevention of venous thromboembolism in hospitalized medically iLL patients comparing rivaroxabAN with enoxaparin) trial, extended-duration rivaroxaban was compared with standard-duration enoxaparin followed by placebo for VTE prevention in 8101 hospitalized acutely ill patients with or without HF. The aim of this analysis was to evaluate the relationship between HF severity and the risk of VTE in MAGELLAN patients.. Hospitalized patients diagnosed with HF were included according to New York Heart Association class III or IV at admission (n=2593). HF severity was determined by N-terminal probrain natriuretic peptide (NT-proBNP) plasma concentrations (median 1904 pg/mL). Baseline plasma D-dimer concentrations ranged from 0.6 to 1.7 μg/L for the less and more severe HF subgroups. Patients with more severe HF had a greater incidence of VTE versus patients with less severe HF, with a significant trend up to Day 10 (4.3% versus 2.2%; P=0.0108) and Day 35 (7.2% versus 4.1%; P=0.0150). Multivariable analysis confirmed that NT-proBNP concentration was associated with VTE risk up to Day 10 (P=0.017) and D-dimer concentration with VTE risk up to Day 35 (P=0.005). The association between VTE risk and HF severity that was observed in the enoxaparin/placebo group was not seen in the extended-duration rivaroxaban group.. Patients with more severe HF, as defined by high NT-proBNP plasma concentration, were at increased risk of VTE. NT-proBNP may be useful to identify high short-term risk, whereas elevated D-dimer may be suggestive of high midterm risk.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00571649.

Topics: Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Heart Failure; Hemorrhage; Hospitalization; Humans; Incidence; Male; Middle Aged; Morpholines; Multivariate Analysis; Predictive Value of Tests; Primary Prevention; Risk Factors; Rivaroxaban; Severity of Illness Index; Thiophenes; Venous Thromboembolism

TB-402 is a long-acting monoclonal antibody that partially inhibits factor VIII. A single administration of TB-402 was effective and well-tolerated for the prevention of venous thromboembolism (VTE) after total knee replacement. In this study, the efficacy and safety of a single administration of TB-402 for the extended prophylaxis of VTE after total hip replacement (THR) was investigated. This was a phase II, randomised, active-controlled, double-blind study that included patients undergoing elective THR surgery. Patients were randomised to TB-402 25 mg or TB-402 50 mg, administered as a single intravenous administration 2-4 hours postoperatively, or to rivaroxaban 10 mg once daily for 35 days. The primary efficacy outcome was total VTE defined as symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) detected by bilateral venography at day 35. The principal safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding until day 35. Total VTE was similar in all groups: 5.3% (95%CI 2.9-9.6), 5.2% (95%CI 2.8-9.3) and 4.7% (95%CI 2.5-8.7) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. All were asymptomatic DVTs. Major or clinically relevant non-major bleedings were observed in 5.8% (95%CI 3.3-9.9), 7.2% (95%CI 4.4-11.6) and 1.4% (95%CI 0.5-4.2) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. In conclusion, TB-402, administered as a single postoperative dose, had a similar efficacy compared to rivaroxaban for the prevention of VTE after THR. The incidence of major and clinically relevant non-major bleeding was higher in the TB-402 groups than in the rivaroxaban group.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Patient Safety; Postoperative Complications; Risk; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Rivaroxaban, a direct factor Xa inhibitor, has demonstrated effectiveness for the management of both venous and arterial thrombosis. This study was designed to investigate the antithrombotic effect of rivaroxaban, with or without acetylsalicylic acid (ASA), in an ex vivo perfusion chamber at both low and high shear rates.. Healthy subjects (N=51) were enrolled in a randomized, crossover (rivaroxaban 5, 10 or 20mg with or without ASA), and parallel-group (compared with ASA plus clopidogrel) study. Thrombi formed on pig aorta strips were measured after a 5-minute perfusion at low and high shear rates with blood from the subjects by measuring D-dimer concentration (for fibrin deposition) and P-selectin content (for platelet deposition).. ASA alone had no impact on thrombus D-dimer levels, whereas rivaroxaban alone at peak concentrations decreased D-dimer levels by 9%, 84% and 65% at low shear rate and 37%, 73% and 74% at high shear rate after doses of 5, 10 and 20mg, respectively. Steady-state ASA plus rivaroxaban 5mg caused a greater reduction in D-dimer levels (63%) than monotherapy at low shear rate. Co-administration of ASA with clopidogrel was associated with a 30% decrease in D-dimer levels at low shear rate and a 14% decrease at high shear rate. No conclusive effect on P-selectin content was observed across the treatment groups.. Rivaroxaban dose-dependently inhibited ex vivo thrombus formation under low and high shear rates. Co-administration of ASA had an additional effect on the antithrombotic action of low-dose rivaroxaban.

Topics: Adolescent; Adult; Animals; Anticoagulants; Aspirin; Cross-Over Studies; Female; Humans; In Vitro Techniques; Male; Middle Aged; Morpholines; Platelet Aggregation; Rivaroxaban; Swine; Thiophenes; Thrombosis; Venous Thromboembolism; Young Adult

Venous thromboembolism (VTE) has a significant impact on healthcare costs but is largely preventable with anticoagulant prophylaxis using low-molecular-weight heparins (LMWHs), such as enoxaparin or dalteparin. Rivaroxaban and dabigatran etexilate are two new oral anticoagulants (NOACs) both compared with enoxaparin in separate trials. A decision analytic model with a healthcare and national payer perspective over a five-year time horizon was used to evaluate the cost-effectiveness of the NOACs for VTE prophylaxis after total hip replacement (THR) or total knee replacement (TKR) in France, Italy and Spain. Efficacy and safety data were obtained from randomised controlled trials of rivaroxaban vs enoxaparin and an indirect statistical comparison for rivaroxaban vs dabigatran. Rivaroxaban demonstrated dominance across all comparisons, indications and countries. In THR, total per-patient costs were reduced by up to €160 in the enoxaparin comparison and €115 in the dabigatran comparison, respectively. In addition, quality-adjusted life-years (QALYs) were increased by up to 0.0011 and 0.0012 in each comparison, respectively. Similarly, total costs were reduced in TKR by up to €137 and €28 in the enoxaparin and dabigatran comparisons, respectively. The total number of QALYs was increased by up to 0.0014 in the enoxaparin comparison and 0.0005 in the dabigatran comparison. The results were driven by costs since the incremental benefits were minimal. Rivaroxaban use could result in substantial healthcare cost savings and improved quality of life. The results are applicable across three European countries with differing healthcare systems so, potentially, could be generalised to a much wider population.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Cost of Illness; Cost-Benefit Analysis; Dabigatran; Direct Service Costs; Enoxaparin; France; Humans; Italy; Models, Theoretical; Morpholines; Postoperative Complications; Pyridines; Quality of Life; Rivaroxaban; Spain; Thiophenes; Venous Thromboembolism

Patients receiving anticoagulants could be at higher risk of compressive haematoma with neuraxial anaesthesia use. The phase III RECORD programme compared rivaroxaban with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement surgery in more than 12,500 patients. This observational analysis evaluated the risk of neuraxial haematoma after neuraxial anaesthesia in patients receiving rivaroxaban or enoxaparin using pooled RECORD1-4 data.. The incidences of intraspinal bleeding or haemorrhagic puncture were recorded as part of the criteria for major bleeding (the primary safety outcome in the RECORD studies). Incidences of allogeneic transfusion and venous thromboembolism by type of anaesthesia were also recorded.. No compressive haematomas occurred in rivaroxaban-treated patients (10 mg once daily started 6-8 h after surgery) who underwent neuraxial anaesthesia (n = 4086). Among enoxaparin-treated patients (n = 4090), one compressive spinal haematoma requiring laminectomy occurred after epidural catheter removal in an elderly female patient with renal insufficiency undergoing total knee replacement. Total venous thromboembolism rates did not differ according to type of anaesthesia.. Although no issues were observed with the use of neuraxial anaesthesia in this population of 4086 patients receiving rivaroxaban after total hip or knee replacement, it is important to remain aware of the risk of compressive haematoma. This may be of particular concern in elderly patients with renal insufficiency receiving an anticoagulant predominantly eliminated via the kidneys.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Hematoma; Humans; Incidence; Male; Middle Aged; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized, double-blind trial, we evaluated the efficacy and safety of oral rivaroxaban administered for an extended period, as compared with subcutaneous enoxaparin administered for a standard period, followed by placebo.. We randomly assigned patients 40 years of age or older who were hospitalized for an acute medical illness to receive subcutaneous enoxaparin, 40 mg once daily, for 10±4 days and oral placebo for 35±4 days or to receive subcutaneous placebo for 10±4 days and oral rivaroxaban, 10 mg once daily, for 35±4 days. The primary efficacy outcomes were the composite of asymptomatic proximal or symptomatic venous thromboembolism up to day 10 (noninferiority test) and up to day 35 (superiority test). The principal safety outcome was the composite of major or clinically relevant nonmajor bleeding.. A total of 8101 patients underwent randomization. A primary efficacy outcome event occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% confidence interval [CI], 0.71 to 1.31; P=0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P=0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001).. In acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. (Funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development; MAGELLAN ClinicalTrials.gov number, NCT00571649.).

Topics: Acute Disease; Administration, Oral; Adult; Aged; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

The RECORD programme compared oral rivaroxaban with enoxaparin for prevention of venous thromboembolism after elective total hip or knee replacement. This analysis compared the safety of concomitant use of specified medications with rivaroxaban and enoxaparin by evaluating postoperative bleeding rates from the pooled RECORD1-4 data.. The co-medications were non-steroidal anti-inflammatory drugs and platelet function inhibitors, including acetylsalicylic acid (no dose restriction). The endpoints evaluated were the composite of major and non-major clinically relevant bleeding and any bleeding occurring after first oral study drug intake. The time relative to surgery was stratified into three time periods: day 1-3, day 4-7 and after day 7. Relative bleeding rate ratios for co-medication use versus non-use were derived using stratified Mantel-Haenszel methods and compared between rivaroxaban and enoxaparin groups.. Co-medication use with rivaroxaban or enoxaparin resulted in non-significant increases in bleeding events. Respective rate ratios were not significantly different between rivaroxaban and enoxaparin for all bleeding endpoints with concomitant use of non-steroidal anti-inflammatory drugs (any bleeding, 1.22 vs 1.22; major and non-major clinically relevant bleeding, 1.28 vs 0.90) and with concomitant use of platelet function inhibitors/acetylsalicylic acid (any bleeding, 1.32 vs 1.40; major and non-major clinically relevant bleeding, 1.11 vs 1.13).. This explorative analysis indicates that there is no significant increase in bleeding risk for rivaroxaban compared with enoxaparin when co-administered with non-steroidal anti-inflammatory drugs or acetylsalicylic acid, although, because of low usage, the experience with platelet function inhibitors (except acetylsalicylic acid) was limited.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Drug Interactions; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Platelet Aggregation Inhibitors; Rivaroxaban; Thiophenes; Venous Thromboembolism

To compare the main efficacy and safety endpoints of the pivotal randomised clinical trials (RCTs) on venous thromboembolism (VTE) prevention after total hip (THR) or knee (TKR) replacement with the new oral anticoagulants (NAs) versus enoxaparin.. A pool-analysis of 10 RCTs that included 32.144 randomised patients was performed. Efficacy outcomes were total VTE and all-cause mortality, major VTE, and proximal DVT. Safety outcomes were major bleeding, and clinically relevant (major or non-major) bleeding.. Overall, a significant effect favouring NAs was found for the primary efficacy outcome (RR 0.71; 95%CI 0.56-0.90), major VTE (RR 0.59; 95%CI 0.41-0.84), and proximal DVT (RR 0.51; 95%CI 0.35-0.76). Compared to enoxaparin 40 mg QD, rivaroxaban showed superiority (RR 0.50; 95%CI 0.34-0.73), followed by apixaban (RR 0.63; 95%CI 0.36-1.01) and dabigatran (RR 1.02; 95%CI 0.86-1.20). There was significant heterogeneity among trials and subgroups analysed for these efficacy outcomes. Major bleeding (RR 1.04; 95% CI 0.74-1.46) and clinically relevant bleeding (RR 1.03; 95%CI 0.88-1.21) was similar with NAs or enoxaparin. Rivaroxaban showed a trend toward more major bleeding episodes than enoxaparin (RR 1.88; 95%CI 0.92-3.82) and apixaban showed the lowest clinically relevant bleeding risk (RR 0.81; 95%CI 0.64-1.01).. Overall, NAs showed more efficacy and same safety when compared to the recommended dose of enoxaparin after THR and TKR. There are little differences in efficacy and bleeding risk among NAs and the type of prophylaxis that should be analysed further.

Topics: Adult; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Hemorrhage; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

No data are available regarding appropriate strategies for the transition of patients undergoing total hip or knee replacement (THR/TKR) surgery from subcutaneous low molecular weight heparin (LMWH) to rivaroxaban. This study determined the pharmacodynamic effects of rivaroxaban on the first day of administration compared with serial administration in patients who had transitioned to rivaroxaban 22-28 hours after the last once-daily LMWH dose (or 12-18 hours after the last twice-daily LMWH dose).. Patients undergoing THR or TKR surgery who had received at least one post-operative LMWH dose were included in this open-label, single-arm, multicentre study. Measurements of anti-Factor Xa activity and prothrombin time were made on the first and third days of daily rivaroxaban administration. The effects of age and renal function on these parameters, and safety and tolerability, were assessed.. Fifty-six patients were enrolled in the Safe, Simple Transitions (SST) study; 52 patients comprised the intention-to-treat population. Mean anti-Factor Xa activity increased slightly but significantly from day 1 to day 3, whereas the area under the concentration-time curve (AUC) was similar on days 1 and 3. Mean prothrombin time was slightly prolonged on day 1 compared with day 3; the AUC was significantly increased (p<0.0001). The pharmacodynamic effects of rivaroxaban were slightly increased in older patients and those with reduced renal function. There were no cases of venous thromboembolism or bleeding and no unexpected adverse events.. Initiating rivaroxaban approximately 12 or 24 hours after the last LMWH dose (as appropriate) provides a simple, well-tolerated transition strategy for thromboprophylaxis in patients undergoing THR/TKR surgery.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Deep vein thrombosis and its most dangerous outcome, pulmonary embolism, are complications with a high incidence in hospitalized patients. In plastic surgery, abdominoplasty is the aesthetic surgery more frequently associated with deep vein thrombosis condition. This study aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after abdominoplasty in patients considered to be at risk.. In a randomized, double-blind study, 40 patients undergoing abdominoplasty were assigned to receive either oral rivaroxaban (10 mg) or oral placebo once daily for 10 days, beginning 6 to 8 hours after surgery.. The study was interrupted after 27 operations due to systematic complications. The population operated on was composed of women with a mean age of 38 years. Most patients were Caucasian (85 percent) and had a mean body mass index of 28. The average overall rate of complications was 29.6 percent (large hematomas requiring drainage), and all complications were seen in the study group, with none in the control group.. Plastic surgery procedures in which large detachment is planned in patients with a moderate risk of deep venous thrombosis should be evaluated with regard to the risk and benefit of thromboembolism prophylaxis. Other measures must be applied and eventually contraindicate a surgical procedure. Further research is needed to complement the data from this work.

Topics: Abdominoplasty; Administration, Oral; Adult; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Follow-Up Studies; Hematoma; Humans; Middle Aged; Morpholines; Postoperative Care; Postoperative Complications; Postoperative Hemorrhage; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

To explore the incidence of postoperative venous thromboembolism (VTE) in adult patients with primary bone tumor undergoing knee operation and evaluate its efficacy and safety in the prevention of VTE.. For this prospective, randomized and negative-control single-center trial, a total of 100 eligible patients were selected and randomly divided into observation and control groups. Observation group (rivaroxaban): the first rivaroxaban tablet was taken in the first 24 hours after operation. Rivaroxaban was administered daily every 24 hours up to Day 14.. no anticoagulant was taken postoperatively.. Efficacy indictors: 6 cases of DVT (an incidence of 12%) occurred in the observation group versus 15 (30%) in the control group. Significant statistical difference existed between two groups (P < 0.05). Furthermore, neither pulmonary embolism nor death was found in either group. Safety indicators:a total of 3 bleeding (1 major and 2 non-major) cases occurred in observation group versus a total of 2 bleeding (no major and 2 non-major) cases in control group. No significant statistical difference existed in bleeding events (P > 0.05). The total incidence of adverse effect was 6% (3/50) in the observation group. The drainage volume of the observation group was a little more than that of the control group. But no significant statistical difference existed in drainage duration (P > 0.05). And there was almost no change in the coagulation system by laboratory examination after oral administration.. With an excellent safety profile and a low incidence of adverse effects, Rivaroxaban is effective and safe in the prevention of VTE in adult patients with primary bone tumor undergoing knee operation.

Topics: Adult; Anticoagulants; Bone Neoplasms; Female; Humans; Knee; Male; Middle Aged; Morpholines; Postoperative Complications; Prospective Studies; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Young Adult

Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; False Positive Reactions; Humans; Lupus Coagulation Inhibitor; Morpholines; Partial Thromboplastin Time; Predictive Value of Tests; Prothrombin Time; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Warfarin

Patients with acute medical illnesses are at increased risk of venous thromboembolism (VTE), a significant cause of morbidity and mortality. Thromboprophylaxis is recommended in these patients but questions remain regarding the optimal duration of therapy. The aim of this study is to determine whether oral rivaroxaban is non-inferior to standard-duration (approximately 10 days) subcutaneous (s.c.) enoxaparin for the prevention of VTE in acutely ill medical patients, and whether extended-duration (approximately 5 weeks) rivaroxaban is superior to standard-duration enoxaparin. Patients aged 40 years or older and hospitalized for various acute medical illnesses with risk factors for VTE randomly receive either s.c. enoxaparin 40 mg once daily (od) for 10 ± 4 days or oral rivaroxaban 10 mg od for 35 ± 4 days. The primary efficacy outcomes are the composite of asymptomatic proximal deep vein thrombosis (DVT), symptomatic DVT, symptomatic non-fatal pulmonary embolism (PE), and VTE-related death up to day 10 + 4 and up to day 35 + 4. The primary safety outcome is the composite of treatment-emergent major bleeding and clinically relevant non-major bleeding. As of July 2010, 8,101 patients from 52 countries have been randomized. These patients have a broad range of medical conditions: approximately one-third were diagnosed with acute heart failure, just under one-third were diagnosed with acute infectious disease, and just under one-quarter were diagnosed with acute respiratory insufficiency. MAGELLAN will determine the efficacy, safety, and pharmacological profile of oral rivaroxaban for the prevention of VTE in a diverse population of medically ill patients and the potential of extended-duration therapy to reduce incidence of VTE.

Topics: Acute Disease; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Female; Heart Failure; Humans; Infections; Male; Middle Aged; Morpholines; Pulmonary Embolism; Respiratory Insufficiency; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Over recent years, research on anticoagulant drugs has been guided by the requirement for convenient administration and a wide therapeutic window to allow fixed dosing without the need for coagulation monitoring. Rivaroxaban is the first of a new class of anticoagulant drugs, the direct, selective inhibitors of Factor Xa. The EINSTEIN-extension study compared rivaroxaban with placebo in patients who completed their standard treatment course after venous thromboembolism (VTE), in whom there was equipoise with respect to the need for continued anticoagulation. After 6-12 months of treatment, rivaroxaban significantly reduced the risk of recurrent VTE at the cost of a moderate increase in bleeding complications. Overall, these results suggest that rivaroxaban can be a valid alternative to warfarin for patients requiring long-term secondary prevention of VTE. However, additional data are needed for special populations including the elderly, patients with cancer, renally impaired patients and morbidly obese patients, all of whom were scarcely represented in this trial.

Topics: Administration, Oral; Anticoagulants; Double-Blind Method; Factor Xa Inhibitors; Hemorrhage; Humans; Middle Aged; Morpholines; Risk; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thromboembolism

This study aimed to evaluate the cost-effectiveness of prophylaxis with rivaroxaban vs. enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR) from the perspective of the Canadian healthcare system. A model was developed that included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with one-year cycles). Transition probabilities were derived from phase III clinical trials comparing rivaroxaban with enoxaparin and published literature. Costs were derived from the Ontario Case Costing Initiative and publicly available sources. Utilities were derived from published literature. The model reported VTE event rates, quality-adjusted life expectancy and direct medical costs over a five-year horizon. Costs are reported in 2007 Canadian Dollars (C$). When rivaroxaban and enoxaparin are compared in patients undergoing THR, rivaroxaban dominates enoxaparin. That is, rivaroxaban is associated with improved health outcomes as measured by increased quality-adjusted life years (QALYs; 0.0006) and fewer symptomatic VTE events (0.0061), and also with lower cost (savings of C$300) per patient. Similarly, rivaroxaban dominates enoxaparin in patients undergoing TKR, achieving a gain of 0.0018 QALYs, a reduction of 0.0192 symptomatic venous thromboembolic events and savings of C$129 per patient. Rivaroxaban is a cost-effective alternative to enoxaparin for VTE prophylaxis in patients undergoing THR and TKR. Over a five-year horizon, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more quality-of-life benefit at a lower cost.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Canada; Cost-Benefit Analysis; Enoxaparin; Follow-Up Studies; Humans; Morpholines; Postoperative Complications; Quality of Life; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Venous Thromboembolism

Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically important efficacy and bleeding outcomes of these 2 new agents versus low-molecular-weight heparin (enoxaparin) is lacking.. We separately pooled efficacy and safety data from 6 phase III randomized trials (18 405 participants) comparing equivalent durations of treatment with enoxaparin (40 mg once daily [od] or 30 mg twice daily) versus dabigatran (220 mg od) or versus rivaroxaban (10 mg od) after hip or knee arthroplasty. Odds ratios (OR) for individual outcomes were calculated for each trial and were pooled using the Mantel-Haenszel method. Compared with dabigatran, enoxaparin had a similar risk of symptomatic venous thromboembolism plus all-cause mortality (0.9% versus 1.1%; OR, 0.76; 95% confidence interval [CI], 0.44 to 1.31; I²=76%) and bleeding (5.0% versus 5.6%; OR, 0.90; 95% CI, 0.71 to 1.15; I²=0%). Compared with rivaroxaban, enoxaparin had a 2-fold higher risk of symptomatic venous thromboembolism plus all-cause mortality (1.2% versus 0.6%; OR, 2.04; 95% CI, 1.32 to 3.17; P<0.001; number needed to treat, 167; I²=0%) but demonstrated a significant lower risk of bleeding (2.5% versus 3.1%; OR, 0.79; 95% CI, 0.62 to 0.99; P=0.049; number needed to harm, 167; I²=0%).. In patients undergoing hip or knee arthroplasty, enoxaparin and dabigatran showed similar rates of efficacy and bleeding. Enoxaparin was less effective than rivaroxaban but had a lower risk of bleeding. These results may have important implications for the choice of prophylactic agent in major joint arthroplasty.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Follow-Up Studies; Hemorrhage; Humans; Morpholines; Postoperative Complications; Prospective Studies; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Withholding Treatment

Total hip/knee replacement surgeries are associated with an increased risk of venous thromboembolism and post-operative thromboprophylaxis has become standard treatment. This study aimed to: (i) assess the impact of hip/knee replacement surgery on ex vivo thrombin generation (TG), prothrombin fragments 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer; (ii) compare the anticoagulant effects of dalteparin and rivaroxaban on TG 24 h after surgery. Haemostatic variables were assessed in plasma samples of 51 patients taken pre-operatively, peri-operatively, and 24 h post-operatively. Prophylaxis, once a day, with dalteparin or rivaroxaban, starting 6–8 h post-operatively, was administered in 25 (14 knee/11 hip) and 26 patients (13 knee/13 hip) respectively. TG, F1 + 2, TAT and D-dimer increased during surgery. Dalteparin patients showed a variable TG response 24 h after surgery: conversely, the effect of rivaroxaban on TG was consistent across individuals. Good correlation was seen between rivaroxaban levels and TG-lag-time (rs = 0·46, P = 0·01); TG-time-to-Peak (rs = 0·53, P = 0·005); TG-peak-thrombin (rs = −0·59, P = 0·001); and TG-velocity-index-rate (rs = −0·61, P = 0·0009). Patients who received rivaroxaban showed a greater decrease of TG, F1 + 2 and TAT (but not D-dimer) than those on dalteparin. TG increases during hip/knee replacement surgery. Rivaroxaban inhibits TG more than dalteparin at 24 h after surgery.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dalteparin; Factor Xa; Female; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Prospective Studies; Rivaroxaban; Thiophenes; Thrombin; Treatment Outcome; Venous Thromboembolism

Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.. We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.. The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).. Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).

Topics: Acenocoumarol; Acute Disease; Administration, Oral; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Injections, Subcutaneous; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

A once-daily dose of rivaroxaban 10 mg, an oral, direct Factor Xa inhibitor, was compared with enoxaparin 40 mg subcutaneously once daily for prevention of venous thromboembolism in three studies of patients undergoing elective hip and knee replacement (RECORD programme). A pooled analysis of data from these studies (n = 9581) showed that rivaroxaban was more effective than enoxaparin in reducing the incidence of the composite of symptomatic venous thromboembolism and all-cause mortality at two weeks (0.4% vs 0.8%, respectively, odds ratio 0.44; 95% confidence interval 0.23 to 0.79; p = 0.005), and at the end of the planned medication period (0.5% vs 1.3%, respectively; odds ratio 0.38; 95% confidence interval 0.22 to 0.62; p < 0.001). The rate of major bleeding was similar at two weeks (0.2% for both) and at the end of the planned medication period (0.3% vs 0.2%). Rivaroxaban started six to eight hours after surgery was more effective than enoxaparin started the previous evening in preventing symptomatic venous thromboembolism and all-cause mortality, without increasing major bleeding.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Young Adult

This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty.. In this randomized, double-blind study, we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery, plus a placebo tablet or injection. The primary efficacy outcome was the composite of deep-vein thrombosis (either symptomatic or detected by bilateral venography if the patient was asymptomatic), nonfatal pulmonary embolism, or death from any cause at 36 days (range, 30 to 42). The main secondary efficacy outcome was major venous thromboembolism (proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death from venous thromboembolism). The primary safety outcome was major bleeding.. A total of 3153 patients were included in the superiority analysis (after 1388 exclusions), and 4433 were included in the safety analysis (after 108 exclusions). The primary efficacy outcome occurred in 18 of 1595 patients (1.1%) in the rivaroxaban group and in 58 of 1558 patients (3.7%) in the enoxaparin group (absolute risk reduction, 2.6%; 95% confidence interval [CI], 1.5 to 3.7; P<0.001). Major venous thromboembolism occurred in 4 of 1686 patients (0.2%) in the rivaroxaban group and in 33 of 1678 patients (2.0%) in the enoxaparin group (absolute risk reduction, 1.7%; 95% CI, 1.0 to 2.5; P<0.001). Major bleeding occurred in 6 of 2209 patients (0.3%) in the rivaroxaban group and in 2 of 2224 patients (0.1%) in the enoxaparin group (P=0.18).. A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. (ClinicalTrials.gov number, NCT00329628.)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

We investigated the efficacy of rivaroxaban, an orally active direct factor Xa inhibitor, in preventing venous thrombosis after total knee arthroplasty.. In this randomized, double-blind trial, 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban, 10 mg once daily, beginning 6 to 8 hours after surgery, or subcutaneous enoxaparin, 40 mg once daily, beginning 12 hours before surgery. The primary efficacy outcome was the composite of any deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause within 13 to 17 days after surgery. Secondary efficacy outcomes included major venous thromboembolism (i.e., proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death related to venous thromboembolism) and symptomatic venous thromboembolism. The primary safety outcome was major bleeding.. The primary efficacy outcome occurred in 79 of 824 patients (9.6%) who received rivaroxaban and in 166 of 878 (18.9%) who received enoxaparin (absolute risk reduction, 9.2%; 95% confidence interval [CI], 5.9 to 12.4; P<0.001). Major venous thromboembolism occurred in 9 of 908 patients (1.0%) given rivaroxaban and 24 of 925 (2.6%) given enoxaparin (absolute risk reduction, 1.6%; 95% CI, 0.4 to 2.8; P=0.01). Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin (P=0.005). Major bleeding occurred in 0.6% of patients in the rivaroxaban group and 0.5% of patients in the enoxaparin group. The incidence of drug-related adverse events, mainly gastrointestinal, was 12.0% in the rivaroxaban group and 13.0% in the enoxaparin group.. Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar rates of bleeding. (ClinicalTrials.gov number, NCT00361894.)

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge. Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin.. 2509 patients scheduled to undergo elective total hip arthroplasty were randomly assigned, stratified according to centre, with a computer-generated randomisation code, to receive oral rivaroxaban 10 mg once daily for 31-39 days (with placebo injection for 10-14 days; n=1252), or enoxaparin 40 mg once daily subcutaneously for 10-14 days (with placebo tablet for 31-39 days; n=1257). The primary efficacy outcome was the composite of deep-vein thrombosis (symptomatic or asymptomatic detected by mandatory, bilateral venography), non-fatal pulmonary embolism, and all-cause mortality up to day 30-42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism. This study is registered at ClinicalTrials.gov, number NCT00332020.. The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group. The primary outcome occurred in 17 (2.0%) patients in the rivaroxaban group, compared with 81 (9.3%) in the enoxaparin group (absolute risk reduction 7.3%, 95% CI 5.2-9.4; p<0.0001). The incidence of any on-treatment bleeding was much the same in both groups (81 [6.6%] events in 1228 patients in the rivaroxaban safety population vs 68 [5.5%] of 1229 patients in the enoxaparin safety population; p=0.25).. Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism, including symptomatic events, in patients undergoing total hip arthroplasty.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Rivaroxaban (Xarelto) is an oral, direct factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. The aim was to compare the population pharmacokinetics (PK) and pharmacodynamics (PD) of twice-daily (bid) and once-daily (od) rivaroxaban in patients undergoing total hip replacement (THR). Blood samples were collected from patients enrolled in two phase IIb, dose-ranging studies undertaken to investigate rivaroxaban for thromboprophylaxis after THR. A sparse sampling technique was used and the samples were pooled for PK and PD analysis, which used non-linear mixed effect modelling. Rivaroxaban PK (samples from 758 patients) were well described by an oral, one-compartment model; age and renal function influenced clearance, and body surface area affected volume of distribution. When comparing the same total daily doses, maximum plasma concentrations of rivaroxaban were higher and minimum plasma concentrations were lower with od dosing, compared with bid dosing; however, the 90% intervals overlapped. The area under the plasma concentration-time curve was 18-30% higher in the od than in the bid study. Prothrombin time in seconds (samples from 1181 patients) correlated with rivaroxaban plasma concentrations in a linear fashion in both studies. In conclusion, the PK and PD of rivaroxaban were predictable when given either bid or od. These findings, along with the suggested efficacy and safety of rivaroxaban in the phase II studies, relative to enoxaparin, supported the selection of a convenient, once-daily 10 mg rivaroxaban dose for investigation in phase III studies.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Factor Xa; Female; Humans; Male; Middle Aged; Morpholines; Prothrombin Time; Rivaroxaban; Thiophenes; Venous Thromboembolism

There is a clinical need for novel oral anticoagulants with predictable pharmacokinetics and pharmacodynamics. Rivaroxaban is an oral direct Factor Xa (FXa) inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. This analysis was performed to characterize the population pharmacokinetics and pharmacodynamics of rivaroxaban in patients participating in two phase II, double-blind, randomized, active-comparator-controlled studies of twice-daily rivaroxaban for the prevention of venous thromboembolism after total hip- or knee-replacement surgery.. Sparse blood samples were taken from all patients participating in the studies (n = 1009). In addition, a subset of patients in the hip study (n = 36) underwent full profiling. Rivaroxaban plasma concentrations, FXa activity and the prothrombin time were determined. Nonlinear mixed-effects modelling was used to model the population pharmacokinetics and pharmacodynamics of rivaroxaban.. An oral one-compartment model described the population pharmacokinetics of rivaroxaban well. On the first postoperative day only, categorization of patients as slow or fast absorbers as a tool to address variability in absorption improved the fit of the model. Clearance of rivaroxaban was lower and more variable on the first postoperative day, and so time was factored into the model. Overall, the only major difference between the models for the hip study and the knee study was that clearance was 26% lower in the knee study, resulting in approximately 30% higher exposure. Residual variability in the models was moderate (37% and 34% in the hip and knee studies, respectively). Plasma concentrations of rivaroxaban increased dose dependently. Pharmacokinetic parameters that were estimated using the models agreed closely with results from full-profile patients in the hip study, demonstrating that rivaroxaban pharmacokinetics are predictable. The pharmacokinetics of rivaroxaban were affected by expected covariates: age affected clearance in the hip study only, haematocrit (on the first postoperative day only) and gender affected clearance in the knee study only, and renal function affected clearance in both studies. Bodyweight affected the volume of distribution in both studies. However, the effects of covariates on the pharmacokinetics of rivaroxaban were generally small, and predictions of 'extreme' case scenarios suggested that fixed dosing of rivaroxaban was likely to be possible. FXa activity and the prothrombin time were both affected by surgery, probably because of perioperative bleeding and intravenous administration of fluids; therefore, time was included in the pharmacodynamic models. In both studies, FXa activity correlated with rivaroxaban plasma concentrations following a maximum effect model, whereas prothrombin time prolongation correlated following a linear model with intercept. The slope of the prothrombin time prolongation correlation was 3.2 seconds/(100 microg/L) in the hip study and 4.2 seconds/(100 microg/L) in the knee study. Both pharmacodynamic models in both studies demonstrated low residual variability of approximately 10%.. This population analysis in patients undergoing major orthopaedic surgery demonstrated that rivaroxaban has predictable, dose-dependent pharmacokinetics that were well described by an oral one-compartment model and affected by expected covariates. Rivaroxaban exposure could be assessed using the prothrombin time, if necessary, but not the international normalized ratio. The findings suggested that fixed dosing of rivaroxaban may be possible in patients undergoing major orthopaedic surgery.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dose-Response Relationship, Drug; Double-Blind Method; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Models, Biological; Morpholines; Nonlinear Dynamics; Prothrombin Time; Rivaroxaban; Sex Factors; Thiophenes; Time Factors; Tissue Distribution; Venous Thromboembolism

Topics: Anticoagulants; Bariatric Surgery; Humans; Rivaroxaban; Venous Thromboembolism

The increased risk of thrombosis and bleeding with an active tumor disease is known as the so-called "thrombo-hemorrhagic syndrome", which places high demands on anticoagulation. There are currently 4 randomized, prospective studies on the use of new, non-vitamin K dependent oral anticoagulants (NOAC) for the treatment of venous thromboembolism (VTE) that have occurred in oncology. The FXa inhibitors rivaroxaban, edoxaban and twice apixaban were each used in individual studies versus the standard therapeutic agent dalteparin. Since there is no direct head-to-head comparison of the FXa inhibitors mentioned within a study, the largest study - always compared to dalteparin - was evaluated for each NOAC. The studies were analyzed with regard to their effectiveness, safety, fatal bleeding rates, the risk of gastrointestinal bleeding (GIB) and other differences using descriptive statistics. With dalteparin, the mean VTE recurrence rate was approximately 9% over a 6-month treatment period. All three FXa inhibitors were not inferior to dalteparin in terms of potency. The VTE recurrence rate was - 2.3% lower in edoxaban and apixaban-treated patients and - 5.0% in rivaroxaban-treated patients. In terms of safety, there was an increased rate of severe bleeding (both + 2.4%) for rivaroxaban and edoxaban compared to dalteparin; in particular, the number of GIBs was significantly increased. In contrast, the number of severe bleeding was not increased for apixaban, as was the case for various bleeding types including GIB. In the Apixaban study, the overall rate of severe GIB, which accounted for about 50% of all severe bleeding, and that of clinically relevant non-severe bleeding, were the lowest. The FXa inhibitors are not inferior to the standard therapy with dalteparin in the VTE recurrence rate in oncological patients. The GIB rate appears to be an important predictive factor for the safety of this group of substances, so that tumor location, gastrointestinal risk factors and other individual criteria should be given greater consideration in future therapy decisions for or against an FXa inhibitor.. Das erhöhte Thrombose- und Blutungsrisiko bei aktiver Tumorerkrankung wird als sog. „thrombo-hämorrhagisches Syndrom“ bezeichnet, welches hohe Anforderungen an die Antikoagulation stellt. Aktuell liegen 4 randomisierte, prospektive Studien zum Einsatz von neuen, nicht Vitamin K-abhängigen oralen Antikoagulantien (NOAK) zur Behandlung von in der Onkologie aufgetretenen venösen Thromboembolien (VTE) vor. Dabei wurden die FXa-Inhibitoren Rivaroxaban, Edoxaban und zweimal Apixaban jeweils in einzelnen Studien gegenüber dem Standardtherapeutikum Dalteparin eingesetzt. Da es keinen direkten Head-to-Head-Vergleich der genannten FXa-Inhibitoren innerhalb einer Studie gibt, wurde zu jedem NOAK die jeweils größte Studie – stets verglichen gegenüber Dalteparin – ausgewertet. Die Studien wurden bzgl. ihrer Wirksamkeit, Sicherheit, fataler Blutungsraten, dem Risiko für gastrointestinale Blutungen (GIB) und sonstiger Unterschiede anhand deskriptiver Statistik analysiert. Unter Dalteparin ergab sich eine mittlere VTE-Rezidivrate von ca. 9% bei einem 6-monatigen Behandlungszeitraum. Alle 3 FXa-Inhibitoren waren gegenüber Dalteparin bezüglich der Wirksamkeit nicht unterlegen. Die VTE-Rezidivrate war bei mit Edoxaban und Apixaban behandelten Patienten um – 2,3% und bei Rivaroxaban um – 5,0% niedriger.Bei der Sicherheit fanden sich – jeweils gegenüber Dalteparin – für Rivaroxaban und Edoxaban eine erhöhte Rate an schweren Blutungen (jeweils +2,4%); insbesondere war hierbei die Zahl GIB deutlich erhöht. Dagegen war für Apixaban die Zahl schwerer Blutungen, wie auch für verschiedene Blutungstypen inkl. GIB, nicht erhöht. In der Apixabanstudie war insgesamt die Rate von schweren GIB, die ca. 50% aller schweren Blutungen ausmachten, und die der klinisch-relevanten nicht schweren Blutungen, am niedrigsten. Die FXa-Inhibitoren sind der Standardtherapie mit Dalteparin in der VTE-Rezidivrate bei onkologischen Patienten nicht unterlegen. Die GIB-Rate scheint ein wichtiger prädiktiver Faktor für die Sicherheit dieser Substanzgruppe zu sein, sodass Tumorlokalisation, gastrointestinale Risikofaktoren und andere individuelle Kriterien in Zukunft stärker bei der Therapieentscheidung für oder gegen einen FXa-Inhibitor berücksichtigt werden sollten.

Topics: Anticoagulants; Dalteparin; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Humans; Neoplasms; Prospective Studies; Rivaroxaban; Venous Thromboembolism

The regimens for factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) vary with venous thromboembolism (VTE) or non-valvular atrial fibrillation (NVAF). The dosage and duration of FXa inhibitor therapy also differ. However, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each FXa inhibitor has not fully been assessed. Trough and peak AXA values, PT, and APTT were measured in 85 patients taking apixaban, 105 patients taking edoxaban, and 27 patients taking rivaroxaban. The patients were further divided into three groups based on the dosage. Each FXa inhibitor showed various ranges of AXA values, and twice-daily use resulted in higher absolute AXA values than once-daily use. AXA values and PT for 20 mg apixaban at both trough and peak times were significantly higher than those for 5 mg or 10 mg. AXA values for 60 mg edoxaban at peak time were significantly higher than those for 15 mg or 30 mg. AXA values for 30 mg of rivaroxaban at both trough and peak times were significantly higher than those for 10 mg or 15 mg. In a nonlinear regression model of the relationship between AXA and PT or APTT, PT was positively correlated with AXA values for each FXa inhibitor. This study obtained trough and peak levels of AXA, PT, and APTT in patients with VTE or NVAF who were administered apixaban, edoxaban, and rivaroxaban.

Topics: Atrial Fibrillation; Factor Xa Inhibitors; Humans; Partial Thromboplastin Time; Prothrombin Time; Rivaroxaban; Venous Thromboembolism

Data on the effectiveness and safety of rivaroxaban for the treatment of patients with venous thromboembolism (VTE) and active cancer are limited in the Japanese real-world setting.. In this subanalysis of the J'xactly study, which was a multicenter, prospective, observational study, we evaluated the effectiveness and safety of rivaroxaban in patients with acute VTE and active cancer (n = 193) versus those without active cancer (n = 823).. Compared with patients without active cancer, those with active cancer demonstrated a significantly different age distribution, with fewer aged <65 and ≥75 years; a lower proportion of women; a lower mean body mass index; and a lower proportion of physical inactivity, injury, thrombophilia, and heart failure. There was no difference in the initial dose distribution of rivaroxaban between patients with and without active cancer. The incidences of recurrence or aggravation of symptomatic VTE and major bleeding were not significantly different [VTE: 1.44 % vs. 2.80 % per patient-year, hazard ratio (HR) 0.50, 95 % confidence interval (CI) 0.18-1.39, p = 0.172; major bleeding: 4.49 % vs. 2.55 % per patient-year, HR 1.80, 95 % CI 0.82-3.95, p = 0.137]. Approximately 10 % of patients with active cancer died at 6 months, with a significantly higher cumulative all-cause mortality rate than those without active cancer (23.29 % vs. 2.03 % per patient-year, HR 11.31, 95 % CI 7.30-17.53, p < 0.001).. In patients with VTE and active cancer, rivaroxaban showed acceptable effectiveness, although clinically significant bleeding remains a concern.. UMIN Clinical Trials Registry number, UMIN000025072.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Neoplasms; Prospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

We assessed the effectiveness and safety of rivaroxaban in patients with isolated distal deep vein thrombosis (IDDVT).. Symptomatic venous thromboembolism (VTE) and major bleeding were assessed.. Short-term, low-dose rivaroxaban seems safe and effective for IDDVT treatment.

Topics: Acute Disease; Anticoagulants; Hemorrhage; Humans; Japan; Prospective Studies; Pulmonary Embolism; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Paediatric clinical practice for treatment of venous thromboembolism (VTE) is based on extrapolation from adult trials with minimal data on anticoagulation efficacy and safety in children. Based on EINSTEIN-Jr clinical trial data, rivaroxaban was approved to treat VTE and prevent its recurrence in children of all ages.. To report the safety and efficacy of rivaroxaban use in paediatric VTE and to present real-world data, specifically about very young children.. We conducted a retrospective observational study at Birmingham Children's Hospital. Data were collected from patients <16 years old who received rivaroxaban after its licensure in the period between March 2021 and June 2022.. Rivaroxaban was used for treatment of acute VTE in 64 patients. Thrombosis was CVC-related in 26 patients, unprovoked in 3, while the rest had one or more risk factors for VTE. Safety and efficacy of rivaroxaban were assessed in 52 patients after excluding patients who were on current rivaroxaban treatment and those who were lost to follow up or stopped rivaroxaban due to intolerance. No bleeding events were reported, and recurrence of thrombosis occurred in only 3.6 %. About 35 % had normalised re-imaging, 40.3 % improved, 9.6 % were unchanged and 11.5 % stopped rivaroxaban without re-imaging. Rivaroxaban was used for secondary VTE prophylaxis in 6 patients in our cohort with no recurrence of thrombosis or bleeding reports.. Our real-world experience confirmed that rivaroxaban was well tolerated, effective and safe. Further real-world data and observational studies are essential to investigate the use of rivaroxaban among different risk groups.

Topics: Adolescent; Adult; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

The aim of this article is to provide an overview of the current literature for direct-acting oral anticoagulant (DOAC) use in pediatric patients and summarize ongoing trials.. In treatment of venous thromboembolism (VTE) in pediatric patients, evidence supports use of both dabigatran and rivaroxaban. Dabigatran has been shown to be noninferior to standard of care (SOC) in terms of efficacy, with similar bleeding rates. Similarly, treatment with rivaroxaban in children with acute VTE resulted in a low recurrence risk and reduced thrombotic burden, without increased risk of bleeding, compared to SOC. Treatment of pediatric cerebral venous thrombosis as well as central venous catheter-related VTE with rivaroxaban appeared to be both safe and efficacious and similar to that with SOC. Dabigatran also has a favorable safety profile for prevention of VTE, and rivaroxaban has a favorable safety profile for VTE prevention in children with congenital heart disease. Many studies with several different DOACs are ongoing to evaluate both safety and efficacy in unique patient populations, as well as VTE prevention.. The literature regarding pediatric VTE treatment and prophylaxis is growing, but the need for evidence-based pediatric guidelines remains. Additional long-term, postauthorization studies are warranted to further elucidate safety and efficacy in clinical scenarios excluded in clinical trials. Additional data on safety, efficacy, and dosing strategies for reversal agents are also necessary, especially as the use of DOACs becomes more common in the pediatric population.

Topics: Administration, Oral; Anticoagulants; Child; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism

Topics: Aged; Aged, 80 and over; Anticoagulants; Cost-Effectiveness Analysis; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Registries; Rivaroxaban; Venous Thromboembolism; Vitamin K

In this article, we have selected four topics that particularly caught our attention during the year 2022, and which are related to anticoagulation, its bleeding complications, and hemophilia. Thus, we discuss the issue of the treatment with rivaroxaban of atrial fibrillation associated with rheumatic valvulopathy, which has been studied in a randomized trial, the intensity of thromboprophylaxis in COVID outpatients and inpatients, and the bleeding risk of anticoagulation in patients with cerebral tumors. Finally, recent data on gene therapy in severe hemophilia A, an upcoming treatment, are discussed.. Dans cet article, nous avons sélectionné 4 sujets qui ont particulièrement retenu notre attention durant l’année 2022, en lien avec l’anticoagulation, ses complications hémorragiques et l’hémophilie. Ainsi, nous abordons le traitement par rivaroxaban de la fibrillation atriale associée à une valvulopathie rhumatismale qui a fait l’objet d’une étude randomisée, l’intensité de la thromboprophylaxie chez les patients hospitalisés ou traités en ambulatoire avec un Covid dont les données se sont bien étoffées, le risque associé à l’anticoagulation chez les patients avec une néoplasie cérébrale et, finalement, la thérapie génique dans l’hémophilie A sévère qui devrait apparaître sur le marché très prochainement.

Topics: Anticoagulants; Atrial Fibrillation; Cardiology; COVID-19; Hemophilia A; Hemostasis; Humans; Rivaroxaban; Stroke; Venous Thromboembolism

An optimal venous thromboembolism prophylaxis agent should balance efficacy and safety. While rivaroxaban provides effective venous thromboembolism prophylaxis after total joint arthroplasty, it may be associated with higher rates of bleeding. This study aimed to compare the safety and efficacy of rivaroxaban to aspirin and enoxaparin.. A large national database was queried for patients who underwent elective primary total hip (THA) or total knee arthroplasty (TKA) from January 2015 through December 2020 who received rivaroxaban, aspirin, or enoxaparin. Multivariate analyses were performed to assess the 90-day risk of bleeding and thromboembolic complications. Among TKA patients identified, 86,721 (10.8%) received rivaroxaban, 408,038 (50.8%) received aspirin, and 108,377 (13.5%) received enoxaparin. Among THA patients, 42,469 (9.5%) received rivaroxaban, 242,876 (54.5%) received aspirin, and 59,727 (13.4%) received enoxaparin.. After accounting for confounding factors, rivaroxaban was associated with increased risk of transfusion (TKA: adjusted odds ratio [aOR] = 2.58, P < .001; THA: aOR 1.64, P < .001), pulmonary embolism (TKA: aOR = 1.25, P = .007), and deep vein thrombosis (TKA: aOR = 1.13, P = .022) compared to aspirin. Compared to enoxaparin, rivaroxaban was associated with an increased risk of combined bleeding events (TKA: aOR = 1.07, P < .001, THA: aOR = 1.11, P < .001), but decreased risk of combined prothrombotic events (THA: aOR = 0.85, P = .036).. Rivaroxaban chemoprophylaxis following TKA and THA was associated with an increased risk of bleeding and prothrombotic complications compared to aspirin and enoxaparin.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Enoxaparin; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism

BackgroundVenous thromboembolism (VTE) is common after bariatric surgery and extended prophylaxis is generally recommended. Low molecular weight heparin is the most commonly used agent but requires patients to be trained to self-inject and is expensive. Rivaroxaban is an oral daily formulation approved for VTE prophylaxis after orthopedic surgery. Efficacy and safety of rivaroxaban has been confirmed in major gastrointestinal resections by several observational studies. We report a single centre experience of using rivaroxaban as an agent for VTE prophylaxis in bariatric surgery. MethodsWe performed prospective cohort study assessing safety and efficacy of rivaroxaban as a medication for VTE prophylaxis in patients undergoing bariatric surgery in a single centre in Kyiv, Ukraine. Patients undergoing major bariatric procedure received perioperative prophylaxis of VTE with subcutaneous low molecular weight heparin and then were switched to rivaroxaban for total of 30 days starting on the 4th postoperative day. Thromboprophylaxis was performed in accordance with the VTE risks derived from the Caprini score. On the 3rd, 30th, 60th day after the operation, the patients underwent ultrasound examination of the portal vein, as well as the veins of the lower extremities. Telephone interviews were conducted 30 and 60 days after the surgery to evaluate the presence of complaints which may be characteristic for VTE as well as to assess compliance with the regimen and to assess patient satisfaction. Outcomes studies were incidence of VTE and adverse events related to rivaroxaban administration.Results110 patients were included in the study from July 2019 to May 2021. The average age of the patients was 43.6 years, the average preoperative BMI was 55 (35 to 75). One hundred and seven patients (97.3%) underwent laparoscopic intervention while three patients (2.7%) underwent laparotomy. Eighty-four patients underwent sleeve gastrectomy and twenty-six patients underwent other procedures, including bypass surgery. Average calculated risk of thromboembolic event was 5-6% based on Caprine index. All patients were treated with extended prophylaxis with rivaroxaban. The average follow-up period for patients was 6 months. There were no clinical or radiological evidence of thromboembolic complications in the study cohort. Overall complication rate was 7.2%, however, only one patient (0.9%) developed subcutaneous hematoma associated with rivaroxaban not requiring intervention. Co

Topics: Adult; Animals; Anticoagulants; Bariatric Surgery; Goats; Heparin, Low-Molecular-Weight; Humans; Postoperative Complications; Prospective Studies; Rivaroxaban; Venous Thromboembolism

Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance.. A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3).. In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.

Topics: Anticoagulants; COVID-19; Decision Making; Fibrinolytic Agents; Hemorrhage; Humans; Iran; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism; Venous Thrombosis; Warfarin

The introduction of direct oral anticoagulants (DOACs) has transformed the treatment of venous thromboembolism (VTE). Large health care databases offer valuable insight into how oral anticoagulants (OACs) are used in clinical practice and may aid in understanding reasons for changes in therapy.. To evaluate prescribing patterns of OACs for patients with VTE and identify clinical events that precede treatment changes.. This retrospective cohort study used data from a public (Medicare fee-for-service) and a commercial (IBM MarketScan) health insurance database on 298 609 patients initiating OACs within 90 days of index VTE hospitalization from January 1, 2009, to December 31, 2020. Statistical analysis was conducted from April to August 2022.. Warfarin and the DOACs rivaroxaban, apixaban, dabigatran, and edoxaban.. Characteristics of patients initiating different OACs, along with trends over time of patients initiating OACs, were compared. Time receiving continuous anticoagulant therapy, patterns of anticoagulant discontinuation (treatment gap of ≥30 days), and treatment switches were assessed. Clinical events in the 30 days preceding treatment modifications were identified.. A total of 203 378 individuals with Medicare (mean [SD] age, 76.9 [7.6] years; 122 554 women [60.3%]) and 95 231 with commercial insurance (mean [SD] age, 57.6 [15.8] years; 47 139 women [49.5%]) were included (N = 298 609). Warfarin was the most frequent OAC prescribed (163 044 [54.6%]), followed by rivaroxaban (66 882 [22.3%]) and apixaban (65 997 [22.1%]). The proportion of patients initiating DOACs increased from 0% in 2010 to 86.8% (22 420 of 25 817) in 2019 for patients with Medicare and 92.1% (4012 of 4357) in 2020 for commercially insured patients. Patients with chronic kidney disease were more likely to initiate warfarin (35 561 [11.9%]) or apixaban (16 294 [5.5%]) than rivaroxaban (10 136 [3.4%]), and those with a history of bleeding were more likely to initiate apixaban (5424 [1.8%]) than rivaroxaban (3007 [1.0%]). Overall, patients received persistent OAC treatment for approximately 6 months (Medicare: median, 175 days [IQR, 76-327 days]; commercial insurance: median, 168 days [IQR, 83-279 days]). A total of 33 011 patients (11.1%) switched anticoagulant therapy within a year. Switching to another anticoagulant was preceded most frequently by codes for a VTE diagnostic procedure (27.2% of all switchers [8983 of 33 011]).. This cohort study using data from 2 US health insurance databases suggests that most patients with VTE continued oral anticoagulant treatment for approximately 6 months. Clinical reasons for modifying anticoagulant therapy were identified in one-third of patients. Identifying reasons for treatment modification is crucial for generating valid evidence on drug safety and effectiveness.

Topics: Adult; Aged; Anticoagulants; Cohort Studies; Female; Humans; Medicare; Middle Aged; Retrospective Studies; Rivaroxaban; United States; Venous Thromboembolism; Warfarin

Ageno W, Bertu L, Bucherini E, et al; RIDTS study group.

Topics: Anticoagulants; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting.. To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients.. The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests.. Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups.. The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.. Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial.. Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19.. O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos.. Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento.. O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Topics: Adult; Anticoagulants; Brazil; COVID-19; Endothelial Cells; Fibrinolytic Agents; Humans; Outpatients; Randomized Controlled Trials as Topic; Rivaroxaban; SARS-CoV-2; Thrombosis; Treatment Outcome; Venous Thromboembolism

We present a female patient with a history of systolic heart failure with an ejection fraction of 25-30%, and unprovoked pulmonary embolism on extended anticoagulation therapy with rivaroxaban who underwent a pericardial window for cardiac tamponade due to hemopericardium in the setting of direct oral anticoagulant (DOAC). The rivaroxaban was held following the pericardial window, and she experienced another episode of pulmonary embolism before the rivaroxaban could be restarted. Currently, there are no guidelines on when to restart anticoagulation postpericardial window for DOAC-associated hemopericardium. Studies are needed to help solve this dilemma.. We present a female patient with a history of systolic heart failure which means their left ventricle was unable to pump blood efficiently. They also have a history of an unprovoked disruption in the flow of blood in the pulmonary arteries or its branches, known as a pulmonary embolism. The patient was on direct oral anticoagulation medication to thin their blood, promoting efficient blood flow and minimizing the risk of clots and blockages. While on this medication, the patient developed a significant collection of blood around the heart, so the medication was withheld and the blood collection was drained. She developed another episode of pulmonary embolism before the medication could be restarted. Healthcare providers need guidance on when to restart anticoagulation medications in these types of patients.

Topics: Anticoagulants; Female; Humans; Pericardial Effusion; Pulmonary Embolism; Rivaroxaban; Thromboembolism; Venous Thromboembolism

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Rivaroxaban; Venous Thromboembolism

The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period.. XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.

Topics: Aged; Anticoagulants; Hemorrhage; Humans; Japan; Product Surveillance, Postmarketing; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Levetiracetam; Male; Pyridones; Rivaroxaban; Stroke; Venous Thromboembolism

Patients with gastrointestinal cancer (GICA) are at high risk for venous thromboembolism (VTE). Data from randomized clinical trials in cancer-associated VTE suggest that direct oral anticoagulants (DOACs) conferred similar or superior efficacy but a heterogeneous safety profile in patients with GICA. We compared the safety and effectiveness of DOACs in patients with GICA and VTE at MD Anderson Cancer Center.. This was a retrospective chart review of patients with GICA and VTE receiving treatment with DOACs for a minimum of 6 months. Primary outcomes were the proportion of patients experiencing major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE. Secondary outcomes were time to bleeding and recurrent VTE.. A cohort of 433 patients with GICA who were prescribed apixaban (n = 300), or rivaroxaban (n = 133) were included. MB occurred in 3.7% (95% confidence interval [CI] 2.1-5.9), CRNMB in 5.3% (95% CI 3.4-7.9), and recurrent VTE in 7.4% (95% CI 5.1-10.3). The cumulative incidence rates of CRNMB and recurrent VTE were not significantly different when comparing apixaban to rivaroxaban.. Apixaban and rivaroxaban had a similar risk of recurrent VTE and bleeding and could be considered as anticoagulant options in selected patients with GICA and VTE.

Topics: Administration, Oral; Anticoagulants; Gastrointestinal Neoplasms; Hemorrhage; Humans; Neoplasm Recurrence, Local; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Giant or large coronary artery aneurysms (CAA) are rare in children, most often secondary to Kawasaki disease, and anticoagulation is recommended to prevent thromboembolism. There are no published pediatric reports on the use of a direct oral anticoagulant for this indication. We describe the anticoagulation management of an 8-year-old boy with a dilated right CAA secondary to Kawasaki disease that has remained stable on rivaroxaban and aspirin, following bleeding complications on enoxaparin and challenges on warfarin. The use of rivaroxaban appears to be safe and effective in the prevention of thrombosis in a pediatric patient with CAA.

Topics: Anticoagulants; Child; Coronary Aneurysm; Coronary Vessels; Humans; Male; Mucocutaneous Lymph Node Syndrome; Rivaroxaban; Venous Thromboembolism

Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada. The primary outcomes of venous thrombosis (VTE) and hemorrhage were identified by validated algorithms using relevant diagnoses and billing codes. Overlap-weighted cause-specific Cox proportional hazard models were used to examine the association of direct oral anticoagulants (DOAC) on the 90-day risk of VTE and hemorrhage compared with low-molecular-weight heparin (LMWH). A total of 27  645 patients were prescribed DOAC (N = 22  943) or LMWH (N = 4702) after arthroplasty. Rivaroxaban was the predominant DOAC (94.5%), while LMWH mainly included enoxaparin (67%) and dalteparin (31.5%). DOAC users had higher eGFRs, fewer co-morbidities, and surgery in more recent years compared to LMWH users. After weighing, DOAC (compared with LMWH) was associated with a lower risk of VTE (DOAC: 1.5% vs. LMWH: 2.1%, weighted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.94) and a higher risk of hemorrhage (DOAC: 1.3% vs. LMWH: 1.0%, weighted HR 1.44, 95% CI 1.04-1.99). Additional analyses including a more stringent VTE defining algorithm, different eGFR cut-offs, and limiting to rivaroxaban and enoxaparin showed consistent findings. Among elderly adults with CKD, DOAC was associated with a lower VTE risk and a higher hemorrhage risk compared to LMWH following hip or knee arthroplasty.

Topics: Adult; Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Ontario; Renal Insufficiency, Chronic; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

To compare the adherence, persistence, discontinuation and switching rates of direct oral anticoagulants (DOACs) for Medicare patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE).. This was retrospective observational cohort study design. Medicare Part D claims files were used for the study duration (2015-2018). Inclusion-exclusion criteria were applied to identify the NVAF and VTE sample using dabigatran, rivaroxaban, apixaban, edoxaban and warfarin during the identification period (2016-2017). Outcomes of adherence, persistence, time to non-persistence and time to discontinuation were assessed in those who did not switch the index drug in the follow-up period (365 days from the index date). Switching rates were assessed in those who switched the index drug at least once in the aforementioned follow-up period. Descriptive statistics were conducted for all the outcomes, and comparisons were made using t-tests, chi-square, and ANOVA. Logistic regression was conducted to compare the odds of being adherent and the odds of switching in NVAF and VTE patient cohorts.. Of all the DOACs, patients with NVAF or VTE were most adherent to apixaban (PDC = 76.88). Among all the DOACs, non-persistence and discontinuation rates were highest for warfarin. Majority of the switches were reported from dabigatran to other DOAC and to apixaban from other DOAC. Despite the better utilization outcomes reported for apixaban users, Medicare plans covered rivaroxaban favorably. It was associated with the lowest mean amount paid by the patient (NVAF: $76; VTE: $59), and the highest mean amount paid by the plans (NVAF: $359; VTE: $326).. Medicare plans need to consider adherence, persistence, discontinuation and switching rates of DOACs to make the coverage decisions.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Medicare; Retrospective Studies; Rivaroxaban; United States; Venous Thromboembolism; Warfarin

Direct oral anticoagulants (DOAC) such as Xa inhibitors rivaroxaban (riva) and apixaban (apix) are increasingly replacing Vitamin K antagonists in prophylaxis and treatment of venous thromboembolism (VTE). Measurements of DOAC plasma levels may be necessary in certain clinical conditions to determine the further dosage. Making decisions is made more difficult by the fact that the peak and trough plasma levels are subject to strong inter-individual fluctuations with overlapping reference ranges. We wanted to find out whether the peak and trough levels can be narrowed if they are determined based on age and gender.. Therefore, we collected data on peak and trough anti-Xa concentrations in patients treated with either rivaroxaban (n = 93) or apixaban (n = 51) in one center. After exclusion of blood samples of uncertain oral intake, 83 samples for rivaroxaban and 49 samples for apixaban remained for further analysis. Differences between male (riva n = 42, apix n = 28) and female (riva n = 41 and apix n = 21) as well as young (≤ 60 years, riva n = 44, apix n = 23) and elder (> 60 years) patients (riva n = 39 and apix n = 26) were analyzed by Student`s t-test and retrospective regression.. We found no differences in age and gender for the apix peak levels. But women had significantly higher riva peak concentrations than men (308.8 ± 178.1 ng/mL versus 206.4 ± 80 ng/mL, p = 0.013). Patients older than 60 years had significantly higher riva peak levels than those younger than 60 (293.7 ± 126.7 ng/mL versus 211.7 ± 158.4 ng/mL, p = 1.29 x 10-8).. In search of narrowing standard peak and trough levels in patients' sera we found significant differ-ences between patients below and above sixty years of age. Gender-associated differences were found in rivaroxa-ban levels possibly explaining DOAC associated hypermenorrhea. In conclusion, gender and age should be included in the determination of peak blood concentration references.

Topics: Administration, Oral; Aged; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Male; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

Topics: Fibrinolytic Agents; Hematologic Neoplasms; Heparin, Low-Molecular-Weight; Humans; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

To assess adherence and persistence to the direct factor Xa inhibitor oral anticoagulants in the community following newly diagnosed venous thromboembolism (VTE).. We retrospectively reviewed community pharmacy dispensing data on all patients with newly diagnosed VTE who were prescribed direct factor Xa inhibitors, apixaban or rivaroxaban, between January 2018 and December 2019 at our institution. Proportion of days covered (PDC) was used to assess adherence at 90 days, and 6- and 12 months. Persistence was measured by participants having both dispensed supply of a factor Xa inhibitor at the end of the treatment period and no significant gaps (maximum of 60 days) in supply.. There were 225 patients identified. Overall PDC at 90 days, 6- and 12 months were 84.6%, 86.2% and 86.1%, respectively. Apixaban had a higher mean overall PDC than rivaroxaban (86.2% and 80.6%, respectively). Females demonstrated higher PDC compared with males (87.3% versus 81.2%). Overall, 133 patients (64%) were persistent with therapy.. In patients with newly diagnosed VTE treated with a factor Xa inhibitor, adherence rates are high at >80%, with females and those prescribed apixaban exhibiting higher adherence. These findings may assist clinicians in identifying those patients with VTE at risk of poor adherence.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Humans; Male; Pharmacies; Pharmacy; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment.. To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years).. A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates.. We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment.. Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism; Warfarin

The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients.. Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t-test) for continuous data.. Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese.. When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Humans; Obesity; Pyridones; Rivaroxaban; Thinness; Venous Thromboembolism; Warfarin

Emulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).. Five landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel-Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.. Compared to trial populations, real-world study populations were older (range: 63-69 years [RWE] vs. 54-59 years [RCT]), with more females (55-60.5% vs. 39-48.3%) and had a higher prevalence of active cancer (4.2-15.4% vs. 2.5-9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70-0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37-0.96; Hokusai-VTE: 0.49, 0.31-0.78; EINSTEIN-DVT: 0.54, 0.33-0.89; EINSTEIN-PE: 0.50, 0.34-0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.. This study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.

Topics: Administration, Oral; Aged; Anticoagulants; Dabigatran; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

Patients with pelvic trauma are at high risk of thromboembolic complications, but effective methods of prophylaxis are still to be accepted widely. The incidence of venous thromboembolism (VTE) has been reported to be as high as 61%, which represents the commonest cause of morbidity and mortality in this cohort. New oral anticoagulants are now available and may be used instead of LMWH injections for extended prophylaxis. Rivaroxaban has not been comprehensively considered in the previous pelvic and acetabular trauma literature, but its known benefits include increased patient compliance, especially in the minority of patients who are unable to self-administer injections, and that it does not require monitoring.. All patients referred to our pelvic trauma service between 2015 and 2020 were considered for this study, exclusion criteria involved those patients who had contraindications to rivaroxaban, those who were referred to our service but were never managed at our centre and those managed by other teams (e.g. neurosurgery). Operative patients were initially managed with LMWH until 24 h post-operatively when they started rivaroxaban. Conservatively managed patients started Rivaroxaban straight away. Data were collected on demographics, injury mechanism, fracture classification and clinically relevant VTE and bleeding events up until 3 months post discharge.. The overall incidence of VTE was 2%. These represented 3 DVTs and 3 PEs, and occurred in patients who were managed operatively. No major bleeding events were observed. There were two minor bleeding events, both occurring in patients who were managed conservatively with rivaroxaban alone, and they did not require further intervention. 90% of patients surveyed expressed preference for oral prophylaxis. Reported compliance with rivaroxaban was 100%.. Our data show that this VTE regimen protocol is safe and effective in this group of injured patients and is at least non-inferior to the standard prophylaxis of LMWH alone.

Topics: Aftercare; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Patient Discharge; Rivaroxaban; Venous Thromboembolism

Direct oral anticoagulant (DOAC)-inhibiting factor Xa (FXa-DOAC) are being increasingly used as prophylaxis of venous thromboembolism and for prevention of stroke in patients with atrial fibrillation. In contrast to vitamin K antagonists, DOACs do not require monitoring in general. However, it is sometimes of value in the acute setting, for instance when considering a reversal agent in uncontrolled bleeding in patients on DOAC.. We evaluated if a low-molecular weight heparin (LMWH)-calibrated anti-factor Xa assay could be used to estimate FXa-DOAC concentration in the concentration range <100 ng/mL by spiking known concentrations of FXa-DOAC and from those result calculate the FXa-DOAC concentration from the response of the LMWH assay. This procedure was then evaluated by comparing the result with a drug-calibrated chromogenic assay and liquid chromatography tandem mass spectrometry (LC-MS/MS) on clinical plasma samples from patients treated with apixaban or rivaroxaban.. Although the measuring range was narrower for the LMWH-calibrated assay, concentrations recalculated from the LMWH assay was comparable with those measured by the drug-calibrated method when compared with LC-MS/MS.. We suggest that an LMWH-calibrated anti-factor Xa assay can be used after characterization of the response of FXa-DOACs to give guidance on the concentration of apixaban and rivaroxaban. Shorter turnaround time than LC-MS/MS and the greater availability than drug-calibrated chromogenic assays could make this a valuable option in the acute setting.

Topics: Atrial Fibrillation; Blood Coagulation Tests; Chromatography, Liquid; Clinical Decision-Making; Disease Management; Disease Susceptibility; Drug Monitoring; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Pyrazoles; Pyridones; Reproducibility of Results; Rivaroxaban; Sensitivity and Specificity; Stroke; Tandem Mass Spectrometry; Venous Thromboembolism

Patients with inflammatory bowel disease (IBD) have a 2- to 3-fold greater risk of venous thromboembolism (VTE) than patients without IBD, with increased risk during hospitalization that persists postdischarge. We determined the cost-effectiveness of postdischarge VTE prophylaxis among hospitalized patients with IBD.. A decision tree compared inpatient prophylaxis alone vs 4 weeks of postdischarge VTE prophylaxis with 10 mg/day of rivaroxaban. Our primary outcome was quality-adjusted life years (QALYs) over 1 year, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2020 $USD), incremental cost-effectiveness ratios (ICERs) and number needed to treat (NNT) to prevent 1 VTE and VTE death were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty.. Prophylaxis with rivaroxaban resulted in 1.68-higher QALYs per 1000 persons compared with no postdischarge prophylaxis at an incremental cost of $185,778 per QALY. The NNT to prevent a single VTE was 78, whereas the NNT to prevent a single VTE-related death was 3190. One-way sensitivity analyses showed that higher VTE risk >4.5% and decreased cost of rivaroxaban ≤$280 can reduce the ICER to <$100,000/QALY. Probabilistic sensitivity analyses favored prophylaxis in 28.9% of iterations.. Four weeks of postdischarge VTE prophylaxis results in higher QALYs compared with inpatient prophylaxis alone and prevents 1 postdischarge VTE among 78 patients with IBD. Although postdischarge VTE prophylaxis for all patients with IBD is not cost-effective, it should be considered in a case-by-case scenario, considering VTE risk profile, costs, and patient preference.

Topics: Anticoagulants; Cost-Benefit Analysis; Hospitalization; Humans; Inflammatory Bowel Diseases; Quality-Adjusted Life Years; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Child; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Risk Factors; Rivaroxaban; Venous Thromboembolism; Vitamin K

Thrombotic complications are common in patients with severe COVID-19 pneumonia with important consequences on the diagnostic and therapeutic management. We report a consecutive series of five patients on long-term oral anticoagulation therapy who presented to our hospital for severe COVID-19 pneumonia associated with segmental acute pulmonary embolism despite adherence to therapy and with an adequate anticoagulant range at the time of the event. Four patients were receiving a direct oral anticoagulant (two with edoxaban, one with rivaroxaban and one with apixaban) and one patient a vitamin K antagonist. No significant thrombotic risk factors, active cancer, or detectable venous thromboembolism were present. In all cases, elevated d-dimer and fibrinogen levels with a parallel rise in markers of inflammation were documented. The combination of these findings seems to support the hypothesis that considers the local vascular damage determined by severe viral infection as the main trigger of thrombi detected in the lungs, rather than emboli from peripheral veins.

Topics: Anticoagulants; COVID-19; COVID-19 Drug Treatment; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

Warfarin is recognized as the standard treatment for thrombotic antiphospholipid syndrome (APS); however, direct oral anticoagulants (DOACs) represent appealing therapeutic alternatives given their lack of monitoring and limited drug interactions. A few randomized controlled trials comparing rivaroxaban with warfarin showed an increased risk of recurrent thromboembolism, specifically arterial thrombosis, in patients with high risk forms of APS such as those that are triple antibody positive. We conducted a single-center, retrospective cohort study of all patients within our health system from 2015 to 2020 with a diagnosis of APS (single or double antibody positive) and history of venous thromboembolism. We sought to compare the proportion of patients with a recurrent thrombosis when prescribed a DOAC versus warfarin. Among 96 patients included, 57 were prescribed warfarin and 39 were prescribed a DOAC (90% rivaroxaban). The proportion of patients with a recurrent thromboembolism was almost three times higher in the DOAC group (15.4%) compared to the warfarin group (5.3%), although this was not statistically significant (p = 0.15). Major bleeding was not different between groups. Our findings suggest that rivaroxaban may pose an increased risk for recurrent thromboembolism in low risk APS patients that are single or double-antibody positive compared to warfarin. Results of our study should be cautiously applied to DOACs besides rivaroxaban given their small representation in this study.

Topics: Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Humans; Retrospective Studies; Rivaroxaban; Thrombosis; Venous Thromboembolism; Warfarin

Rivaroxaban is a viable anticoagulant for the management of cancer-associated venous thromboembolism (CA-VTE). A previously verified physiologically-based pharmacokinetic (PBPK) model of rivaroxaban established how its multiple pathways of elimination via both CYP3A4/2J2-mediated hepatic metabolism and organic anion transporter 3 (OAT3)/P-glycoprotein-mediated renal secretion predisposes rivaroxaban to drug-drug-disease interactions (DDDIs) with clinically relevant protein kinase inhibitors (PKIs). We proposed the application of PBPK modelling to prospectively interrogate clinically significant DDIs between rivaroxaban and PKIs (erlotinib and nilotinib) for dose adjustments in CA-VTE.. The inhibitory potencies of the PKIs on CYP3A4/2J2-mediated metabolism of rivaroxaban were characterized. Using prototypical OAT3 inhibitor ketoconazole, in vitro OAT3 inhibition assays were optimized to ascertain the in vivo relevance of derived transport inhibitory constants (K. Mechanism-based inactivation (MBI) of CYP3A4-mediated rivaroxaban metabolism by both PKIs and MBI of CYP2J2 by erlotinib were established. The importance of substrate specificity and nonspecific binding to derive OAT3-inhibitory K. We established a PBPK-DDDI model to prospectively evaluate clinically relevant interactions between rivaroxaban and PKIs for the safe and efficacious management of CA-VTE.

Topics: Cytochrome P-450 CYP3A; Drug Interactions; Erlotinib Hydrochloride; Humans; Ketoconazole; Models, Biological; Neoplasms; Prospective Studies; Protein Kinase Inhibitors; Rivaroxaban; Venous Thromboembolism

Apixaban and rivaroxaban are replacing vitamin K antagonists for the treatment of venous thromboembolism (VTE) in adults; however, head-to-head comparisons remain limited.. To assess the effectiveness and safety of apixaban compared with rivaroxaban in patients with VTE.. Retrospective new-user cohort study.. U.S.-based commercial health care insurance database from 1 January 2015 to 30 June 2020.. Adults with VTE who were newly prescribed apixaban or rivaroxaban.. The primary effectiveness outcome was recurrent VTE, a composite of deep venous thrombosis and pulmonary embolism. The primary safety outcome was a composite of gastrointestinal and intracranial bleeding.. Of 49 900 eligible patients with VTE, 18 618 were new users of apixaban and 18 618 were new users of rivaroxaban. Median follow-up was 102 days (25th, 75th percentiles: 30, 128 days) among apixaban and 105 days (25th, 75th percentiles: 30, 140 days) among rivaroxaban users. After propensity score matching, apixaban (vs. rivaroxaban) was associated with a lower rate for recurrent VTE (hazard ratio, 0.77 [95% CI, 0.69 to 0.87]) and bleeding (hazard ratio, 0.60 [CI, 0.53 to 0.69]). The absolute reduction in the probability of recurrent VTE with apixaban versus rivaroxaban was 0.006 (CI, 0.005 to 0.011) within 2 months and 0.011 (CI, 0.011 to 0.013) within 6 months of initiation. The absolute reduction in the probability of gastrointestinal and intracranial bleeding with apixaban versus rivaroxaban was 0.011 (CI, 0.010 to 0.011) within 2 months and 0.015 (CI, 0.013 to 0.015) within 6 months of initiation.. Short follow-up.. In this population-based cohort study, patients with VTE who were new users of apixaban had lower rates for recurrent VTE and bleeding than new users of rivaroxaban.. None.

Topics: Aged; Cerebral Hemorrhage; Databases, Factual; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Male; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Risk Factors; Rivaroxaban; United States; Venous Thromboembolism

The choice of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) is at the physician's discretion; however, it is useful to know the differences in the clinical data of DOACs to help physicians choose.. We aimed to compare the mortality associated with the use of rivaroxaban, edoxaban, and apixaban in clinical practice.. We identified 38,245 patients with first hospitalization for VTE from the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). We classified patients into three groups by DOAC (rivaroxaban and edoxaban group, rivaroxaban and apixaban group, and edoxaban and apixaban group) and compared the in-hospital mortality and bleeding risk by propensity score (PS) matching in each group.. After PS matching, patients with rivaroxaban use had significantly lower total in-hospital mortality (1.2% vs. 2.1%; odds ratio [OR] 0.55, p = 0.012) and in-hospital mortality within 21 days (0.4% vs. 1.0%; OR 0.41, p = 0.020) and 28 days (0.7% vs. 1.3%; OR 0.53, p = 0.042) than patients with apixaban use. In the subanalysis, significant differences were only observed in patients younger than 80 years of age, patients with pulmonary embolism, and patients without heart failure. There was no significant difference in in-hospital mortality in the other groups and in the rate of bleeding events among the three groups.. On PS-matched analysis, there was a difference in in-hospital mortality, especially in the rivaroxaban and apixaban group. Identifying the clinical characteristics of patients associated with each DOAC, as well as prognosis, will be useful in determining treatment strategies for VTE.

Topics: Administration, Oral; Anticoagulants; Hospital Mortality; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism

Recent reports suggest that direct oral anticoagulants (DOAC) may induce different anticoagulant and profibrinolytic responses. We performed a head-to-head comparison of the changes in thrombin generation (TG) parameters and tissue plasminogen activator (t-PA)-induced clot lysis produced by different DOAC.. We tested 137 plasma samples from patients with non-valvular atrial fibrillation (n=72) and venous thromboembolism (n=65) under treatment with apixaban (n=38), edoxaban (n=29), rivaroxaban (n=39), or dabigatran (n=31). TG was evaluated by a fluorometric assay and fibrinolysis by measuring the lysis time of clots exposed to 40 ng/mL t-PA.. Trough-to-peak changes of TG parameters, along with correlation analysis, showed that all DOAC prolonged the lag-time in a concentration-dependent fashion. As for the other parameters, anti-factor Xa drugs markedly reduced the thrombin peak and velocity index but had little (rivaroxaban) or no effect on endogenous thrombin potential (ETP); dabigatran, instead, reduced ETP, weakly decreased thrombin peak and did not influence the velocity index, as also inferred from the changes in TG values after neutralisation of dabigatran with idarucizumab. Concerning the profibrinolytic effect of DOAC, intergroup comparison showed that the clot lysis time of dabigatran samples was significantly shorter than that of the apixaban and rivaroxaban samples, at both C-Trough and C-Peak. Moreover, a significant correlation between trough-to-peak changes in drug level and clot lysis time was only observed in the dabigatran group (rho=0.53). Finally, after DOAC removal by DOAC-stop, only dabigatran samples showed a significant increase in lysis time.. Our data show that dabigatran inhibits TG in a different way than anti-Xa DOAC; moreover, under our conditions, only dabigatran displayed profibrinolytic activity, most likely because of its distinctive effect on the TG curve.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Fibrin Clot Lysis Time; Fibrinolysis; Humans; Rivaroxaban; Thrombin; Tissue Plasminogen Activator; Venous Thromboembolism

 Data from clinical trials indicate that direct oral anticoagulants (DOACs) are noninferior and safer than conventional therapy (low-molecular-weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting..  This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013 to 2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional hazards regression was used to estimate adjusted hazard ratios of the endpoints..  A total of 58,137 patients were included (10,775 VKAs, 10,440 apixaban, 36,922 rivaroxaban). Propensity score-matched cohort sizes were 7,503 for apixaban and 9,179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32-0.59]), all-cause death (0.61 [0.51-0.74]), and first recurrent VTE (0.67 [0.52-0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53-0.74]) but not for bleeding requiring hospitalization (0.86 [0.69-1.07]) or first recurrent VTE (0.91 [0.74-1.13])..  Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.

Topics: Administration, Oral; Adult; Anticoagulants; Cohort Studies; Hemorrhage; Humans; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Special aspects of anticoagulation in children include the different epidemiology of thrombosis, developmental changes in the coagulation system, age-dependent pharmacokinetics of anticoagulants, risk of bleeding, and practical hurdles to anticoagulation. The classical anticoagulants so far used in children have several limitations, resulting in the need for regular monitoring. The pharmacological properties of direct oral anticoagulants (DOACs) and the special challenges of anticoagulation in children make the DOACs particularly attractive for children. All DOACs have pediatric development programs, targeting various indications for prevention and treatment of thrombosis. Child-appropriate formulations have been developed, age-specific dosing information generated, and safety and efficacy evaluated in ongoing phase 3 trials. Rivaroxaban and dabigatran have already been authorized for children for treatment of acute venous thrombosis and for extended secondary prevention. Their safety and efficacy have been demonstrated comparable to that of standard-of-care anticoagulants, without need for monitoring. Further studies are ongoing, which are expected to lead to pediatric authorizations of DOACs for primary venous thromboembolic event prevention in some high-risk settings. More real-life data will be necessary from postmarketing studies and registries to complement the evidence base for DOAC use in children, particularly in the youngest age groups and special disease populations.. Spezielle Aspekte der Antikoagulation bei Kindern umfassen die unterschiedliche Epidemiologie von Thrombosen, entwicklungsbedingte Veränderungen im Gerinnungssystem, altersabhängige Pharmakokinetik von Antikoagulantien, Blutungsrisiko und praktische Hürden für die Antikoagulation. Die bislang bei Kindern eingesetzten klassischen Antikoagulantien haben zahlreiche Limitationen, weswegen sie regelmäßiges Monitoring erfordern.Die pharmakologischen Eigenschaften der direkten oralen Antikoagulantien (DOAKs) und die speziellen Herausforderungen von Antikoagulation bei Kindern machen die DOAKs für Kinder besonders attraktiv. Alle DOAKs haben pädiatrische Entwicklungsprogramme, die auf verschiedene Indikationen von Prävention und Behandlung von Thrombosen abzielen. Kindergerechte pharmazeutische Formulierungen wurden entwickelt, altersspezifische Dosisinformation generiert, und Sicherheit und Wirksamkeit werden in laufenden Phase 3 Studien evaluiert.Rivaroxaban und Dabigatran erhielten bereits Zulassungen für Kinder für die Behandlung der akuten Venenthrombose und längerfristige sekundäre Prophylaxe. Ihre Sicherheit und Wirksamkeit zeigten sich jener von Standardantikoagulantien vergleichbar, ohne die Notwendigkeit für Monitoring. Weitere Studien sind noch am Laufen, welche voraussichtlich zu pädiatrischen Zulassungen von DOAKs für primäre Thromboprophylaxe in verschiedenen Hochrisikosituationen führen werden. Im Weiteren werden noch mehr Daten aus der Anwendung in der Praxis aus Postmarketing-Studien und Registern erforderlich sein, um die Evidenzbasis für die Anwendung von DOAKs bei Kindern zu erweitern, besonders für die jüngsten Altersgruppen und Kinder mit speziellen Erkrankungen.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Child; Dabigatran; Humans; Rivaroxaban; Venous Thromboembolism

Severely injured patients are at particularly high risk for venous thromboembolism (VTE). Although thromboprophylaxis (PPX) is employed during the inpatient period, patients may continue to be at high risk after discharge. Comparative evidence from surgical subspecialities (eg oncology) reveals benefits of postdischarge (ie extended) PPX. We hypothesized that an extended, postinjury oral thromboprophylaxis regimen would be cost-effective.. A cost-utility model compared no PPX with a 30-day course of apixaban, dabigatran, enoxaparin, fondaparinux, or rivaroxaban in trauma patients. Immediate events including deep venous thrombosis, pulmonary embolus, or bleeding within 30 days of injury were modeled in a decision tree with patients entering a Markov process to account for sequelae of VTE, including postthrombotic syndrome and chronic thromboembolic pulmonary hypertension. Effectiveness was measured in quality-adjusted life years. One-way and probabilistic sensitivity analyses were performed to identify conditions under which the preferred PPX strategy changed.. Rivaroxaban was the dominant strategy (ie less costly and more effective) compared with no PPX or alternative regimens, delivering 30.21 quality-adjusted life years for $404,546.38. One-way sensitivity analyses demonstrated robust preference for rivaroxaban. When examining only patients with moderate-high or high VTE Risk Assessment Profile scores, rivaroxaban remained the preferred strategy. Probabilistic sensitivity analysis demonstrated a preference for rivaroxaban in 100% of cases at a standard willingness-to-pay threshold of $100,000/quality-adjusted life year.. A 30-day course of rivaroxaban is a cost-effective extended thromboprophylaxis strategy in trauma patients in this theoretical study. Prospective studies of postdischarge thromboprophylaxis to prevent postinjury VTE are warranted.

Topics: Aftercare; Anticoagulants; Cost-Benefit Analysis; Humans; Patient Discharge; Prospective Studies; Rivaroxaban; Venous Thromboembolism

Polypharmacy, including use of inhibitors of CYP3A4 and P-glycoprotein (P-gp), is common in patients with venous thromboembolism (VTE) and is associated with increased bleeding.. In 8246 patients included in the EINSTEIN-VTE studies for acute VTE, we evaluated the effect of polypharmacy on bleeding and on the relative differences between rivaroxaban and enoxaparin/vitamin K antagonist (VKA). We assessed the incidence of clinically relevant bleeding (major and clinically relevant nonmajor bleeding) by number of comedications (none, 1-3, ≥4) at baseline, and by use of CYP3A4 and/or P-gp inhibitors. Interaction between rivaroxaban versus enoxaparin/VKA and comedication was assessed by Cox regression analysis with p. We conclude that fixed-dose rivaroxaban as compared with enoxaparin followed by dose-adjusted VKA is not associated with an increased bleeding risk in patients with VTE administered polypharmacy in general and CYP3A4 and/or P-gp inhibitors specifically. This implies that the observed increased bleeding risks with polypharmacy and use of CYP3A4 and/or P-gp inhibitors are likely explained by comorbidities and frailty, and not by pharmacokinetic interactions.

Topics: Anticoagulants; Cytochrome P-450 CYP3A; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Polypharmacy; Rivaroxaban; Venous Thromboembolism; Vitamin K

Guidelines for managing venous thromboembolism (VTE) recommend at least 90 days of therapy with oral anticoagulants. Limited evidence exists about the optimal drug for continuing therapy beyond 90 days.. To compare having prescriptions dispensed for apixaban, rivaroxaban, or warfarin after an initial 90 days of anticoagulation therapy for the outcomes of hospitalization for recurrent VTE, major bleeding, and death.. This exploratory retrospective cohort study used data from fee-for-service Medicare (2009-2017) and from 2 commercial health insurance (2004-2018) databases and included 64 642 adults who initiated oral anticoagulation following hospitalization discharge for VTE and continued treatment beyond 90 days.. Apixaban, rivaroxaban, or warfarin prescribed after an initial 90-day treatment for VTE.. Primary outcomes included hospitalization for recurrent VTE and hospitalization for major bleeding. Analyses were adjusted using propensity score weighting. Patients were followed up from the end of the initial 90-day treatment episode until treatment cessation, outcome, death, disenrollment, or end of available data. Weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs.. The study included 9167 patients prescribed apixaban (mean [SD] age, 71 [14] years; 5491 [59.9%] women), 12 468 patients prescribed rivaroxaban (mean [SD] age, 69 [14] years; 7067 [56.7%] women), and 43 007 patients prescribed warfarin (mean [SD] age, 70 [15] years; 25 404 [59.1%] women). The median (IQR) follow-up was 109 (59-228) days for recurrent VTE and 108 (58-226) days for major bleeding outcome. After propensity score weighting, the incidence rate of hospitalization for recurrent VTE was significantly lower for apixaban compared with warfarin (9.8 vs 13.5 per 1000 person-years; HR, 0.69 [95% CI, 0.49-0.99]), but the incidence rates were not significantly different between apixaban and rivaroxaban (9.8 vs 11.6 per 1000 person-years; HR, 0.80 [95% CI, 0.53-1.19]) or rivaroxaban and warfarin (HR, 0.87 [95% CI, 0.65-1.16]). Rates of hospitalization for major bleeding were 44.4 per 1000 person-years for apixaban, 50.0 per 1000 person-years for rivaroxaban, and 47.1 per 1000 person-years for warfarin, yielding HRs of 0.92 (95% CI, 0.78-1.09) for apixaban vs warfarin, 0.86 (95% CI, 0.71-1.04) for apixaban vs rivaroxaban, and 1.07 (95% CI, 0.93-1.24) for rivaroxaban vs warfarin.. In this exploratory analysis of patients prescribed extended-duration oral anticoagulation therapy after hospitalization for VTE, prescription dispenses for apixaban beyond 90 days, compared with warfarin beyond 90 days, were significantly associated with a modestly lower rate of hospitalization for recurrent VTE, but no significant difference in rate of hospitalization for major bleeding. There were no significant differences for comparisons of apixaban vs rivaroxaban or rivaroxaban vs warfarin.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Hospitalization; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Time Factors; Venous Thromboembolism; Warfarin

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Extended thromboprophylaxis has not been widely implemented in acutely ill medical patients because of bleeding concerns. The MAGELLAN (Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Medically Ill Patients Comparing Rivaroxaban With Enoxaparin) and MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) trials evaluated whether rivaroxaban compared with enoxaparin or placebo could prevent venous thromboembolism without increased bleeding. We hypothesized that patients with major bleeding but not those with nonmajor clinically relevant bleeding would be at an increased risk of all-cause mortality (ACM).. We evaluated all bleeding events in patients taking at least 1 dose of study drug and their association with ACM in 4 mutually exclusive groups: (1) no bleeding, or first event was (2) nonmajor clinically relevant bleeding, (3) major bleeding, or (4) trivial bleeding. Using a Cox proportional hazards model adjusted for differences in baseline characteristics associated with ACM, we assessed the risk of ACM after such events.. Compared with patients with no bleeding, the risk of ACM for patients with nonmajor clinically relevant bleeding was not increased in MARINER (hazard ratio, 0.43;. Patients with major bleeding had an increased risk of ACM, whereas nonmajor clinically relevant bleeding was not consistently associated with an increased risk of death. These results inform the risk-benefit calculus of extended thromboprophylaxis in medically ill patients.. URL: https://www.. gov; Unique identifier: MAGELLAN, NCT00571649. URL: https://www.. gov; Unique identifier: MARINER, NCT02111564.

Topics: Aftercare; Anticoagulants; Enoxaparin; Hemorrhage; Humans; Patient Discharge; Rivaroxaban; Venous Thromboembolism

Primary and recurrent venous thromboembolism (VTE) commonly occur in patients with cancer. However, because of the National Health Insurance regulations, available dosage forms, and clinical conditions, the prescribed dose of rivaroxaban may not be consistent with its recommended dose.. To evaluate the 6-month recurrence rate of VTE and safety of rivaroxaban for patients with cancer.. Patients with new cancer diagnosis or recurrence from 2014 to 2018 who initiated rivaroxaban for VTE from January 2015 to January 2019 were included. We set the rivaroxaban initiation date as the index date and followed up the patients for 180 days. We collected information regarding the starting and maintenance dose/frequency and the treatment duration. The efficacy outcome was the recurrence of VTE within 180 days. The safety outcome included the major bleeding rate and clinically relevant nonmajor bleeding (CRNMB) rate.. Approximately, 46.2% of the 65 included patients received a standard starting dose, and 45% of patients received a maintenance dose above 15 mg (median: 23.9 and 13.1 mg per day, respectively). Two-thirds of the patients stopped treatment within 180 days. Recurrent VTE occurred in 2 (3.1%) patients within 6 months. The major bleeding rate was 7.7%, and the CRNMB rate was 3.1%.. The 6-month recurrence rate of VTE and safety profile were similar between the lower and standard dose of rivaroxaban. This result may be applied to the institutions with dosage availability limited by formulary regulation and patients who cannot use full dose because of clinical considerations.

Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Recurrence; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Rivaroxaban is a first-line option for the management of venous thromboembolism (VTE). However, limited data are available regarding its effectiveness in morbidly obese patients.. To evaluate rates of thrombosis and bleeding in morbidly obese patients receiving rivaroxaban or warfarin for VTE.. A multicenter, retrospective cohort study was conducted to compare rates of bleeding and thrombosis in patients receiving rivaroxaban versus warfarin for acute VTE. Patients were included if they were older than 18 years and had a body mass index (BMI) greater than 40 kg/m. A total of 1281 patients were identified for acute VTE and were included in this study with 487 patients receiving rivaroxaban and 785 receiving warfarin. The average cohort age was 57.6 ± 14.6 years, and the average weight was 136.4 ± 27.2 kg. After controlling for confounding factors, the use of rivaroxaban was not associated with an increased hazard of VTE events when compared with warfarin (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.42-1.08,. No difference was observed in obese patients with weight >120 kg or BMI >40 kg/m

Topics: Adult; Aged; Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Middle Aged; Obesity, Morbid; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Prior observational studies suggest rivaroxaban is safe and effective among patients with morbid obesity who suffered a venous thromboembolism (VTE) event, but existing data are more limited in the broader population of VTE patients with obesity. This study assessed VTE recurrence, major bleeding, healthcare resource utilization, and healthcare costs among VTE patients with obesity who received rivaroxaban versus warfarin. VTE patients with obesity who initiated rivaroxaban or warfarin after a first VTE (index date) were identified from the IQVIA PharMetrics® Plus database (01/02/2011-09/30/2019). The follow-up period spanned from the index date until health plan disenrollment, end of data availability, cancer diagnosis/treatment, end of the 12 month post-index period, or (for the analysis of major bleeding) anticoagulant discontinuation or switch. Patient characteristics were balanced using inverse probability of treatment weighting. The weighted rivaroxaban (N = 8666) and warfarin cohorts (N = 5946) were well balanced (mean age = 51 years, females = 52%). Over a 9.6 months mean observation period, rivaroxaban users had a significantly lower risk of VTE recurrence [7.0% vs. 8.2%, HR(95% CI) = 0.85(0.75;0.97)] and a similar risk of major bleeding [4.1% vs. 3.6%, HR(95% CI) = 1.11(0.89;1.37)] relative to warfarin users at 12 months. Relative to warfarin users, rivaroxaban users had significantly fewer all-cause outpatient visits [RR(95% CI) = 0.71(0.70;0.74)]. The higher pharmacy costs incurred by rivaroxaban recipients (cost difference = $1252) were offset by lower medical costs (cost difference = - $2515, all p < 0.05) compared with warfarin recipients. Our findings suggest that rivaroxaban is safe and effective versus warfarin, and associated with lower medical costs among VTE patients with obesity.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Health Care Costs; Hemorrhage; Humans; Middle Aged; Obesity, Morbid; Retrospective Studies; Rivaroxaban; United States; Venous Thromboembolism; Warfarin

Rivaroxaban is approved in various regions for the treatment of acute venous thromboembolism (VTE) in children aged between 0 and 18 years and was recently investigated for thromboprophylaxis in children aged between 2 and 8 years (with body weights <30 kg) with congenital heart disease who had undergone the Fontan procedure. In the absence of clinical data, rivaroxaban doses for thromboprophylaxis in post-Fontan children aged 9 years and older or ≥30 kg were derived by a bridging approach that used physiologically-based pharmacokinetic (PBPK) and population pharmacokinetic (popPK) models based on pharmacokinetic (PK) data from 588 pediatric patients and from adult patients who received 10 mg once daily for thromboprophylaxis after major orthopedic surgeries as a reference. Both models showed a tendency toward underestimating rivaroxaban exposure in post-Fontan patients aged between 2 and 5 years but accurately described rivaroxaban PK in post-Fontan patients aged between 5 and 8 years. Under the assumption that hepatic function is not impaired in post-Fontan patients, PBPK and popPK simulations indicated that half of the rivaroxaban doses for the same body weight given to pediatric patients treated for acute VTE would yield in pediatric post-Fontan patients exposures similar to the exposure observed in adult patients receiving 10 mg rivaroxaban once daily for thromboprophylaxis. Simulation-derived doses (7.5 mg rivaroxaban once daily for body weights 30-<50 kg and 10 mg once daily for body weights ≥50 kg) were therefore included in the recent US label of rivaroxaban for thromboprophylaxis in children aged 2 years and older with congenital heart disease who have undergone the Fontan procedure.

Topics: Adolescent; Adult; Anticoagulants; Body Weight; Child; Child, Preschool; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Rivaroxaban; Venous Thromboembolism

Several cases of venous thromboembolism in patients treated with direct oral anticoagulants (DOACs) have been reported in the literature, but a quantative analysis of postmarketing reports is lacking. The objective of this study was to determine the post-marketing odds ratio (OR) and reporting odds ratio (ROR) of venous thromboembolism in patients receiving DOACs compared among each other and to vitamin K antagonists (VKAs).. The OR and ROR were used to determine the ratio of reports for deep vein thrombosis and pulmonary embolism between 1 January, 2012 and 15 November, 2020 using the World Health Organization VigiLyze database. This was performed using all venous thromboembolism events in which a DOAC or a VKA was the suspected medication. The OR and ROR including 95% confidence intervals were calculated for each DOAC drug in comparison to all VKAs as a group.. The OR of deep vein thrombosis was highest for rivaroxaban compared with dabigatran and apixaban [2.63 (2.41-2.89); 1.84 (1.72-1.97)]. The OR of deep vein thrombosis was lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.44 (0.32-0.61); 0.31 (0.22-0.42); 0.17 (0.12-0.23)]. The OR of pulmonary embolism was also highest for rivaroxaban compared with dabigatran and apixaban [2.59 (2.37-2.83); 1.79 (1.68-1.92)]. The OR of pulmonary embolism was also lowest for edoxaban compared with dabigatran, apixaban and rivaroxaban [0.77 (0.60-0.97); 0.59 (0.41-0.67); 0.30 (0.23-0.37)]. Comparing RORs of various DOACs with VKAs, rivaroxaban had the highest RORs for deep vein thrombosis/pulmonary embolism, in comparison to apixaban, dabigatran and edoxaban.. Our findings may indicate a higher association between rivaroxaban therapy and venous thromboembolism as compared with apixaban, dabigatran and edoxaban. These findings are uncertain owing to the reliability of a post-marketing registration system that is negatively influenced by a high level of under-reporting. However, based on pharmacodynamics, we cannot exclude the possibility that there is a real effect that may be driven by non-adherence.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Pulmonary Embolism; Pyridones; Reproducibility of Results; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; World Health Organization

Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to measure the impact of DOACs compared to warfarin on safety and efficacy outcomes in extreme body weight patients. This multi-center, health system, retrospective study examined the outcomes of patients with all body weights and extreme body weights prescribed a DOAC (rivaroxaban, apixaban, dabigatran, edoxaban) or warfarin for atrial fibrillation or venous thromboembolism over a 9-year period. The primary outcome was a composite of thromboembolism, symptomatic recurrent VTE, or severe bleeding; analyzed by pre-determined BMI cutoffs. A total of 19,697 patients were included in the study: 11,604 in the DOAC group and in the 8093 in the warfarin group. 295 patients were underweight and 9108 patients were pre-obese to obese class 3. After adjusting for potential confounders, warfarin patients had higher odds of experiencing the composite outcome compared to DOAC patients (OR 1.337, 95% CI 1.212-1.475). Additionally, obese patients were 24.6% more likely to experience the outcome compared to normal BMI patients. Adjusted modeling showed that warfarin patients experienced higher bleed rates compared to DOAC patients (OR 1.432, 95% CI 1.266-1.620). Obese patients were less likely to be diagnosed with a bleed (OR 0.749, 95% CI 0.658-0.854), and underweight patients were more likely to be diagnosed with a bleed (OR 1.522, 95% CI 1.095-2.115) compared to normal BMI patients. In conclusion, DOACs for atrial fibrillation or VTE in patients with extreme body weights appear safe and effective when compared to warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Obesity, Morbid; Retrospective Studies; Rivaroxaban; Stroke; Thinness; Venous Thromboembolism; Warfarin

Topics: Aspirin; Atherosclerosis; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Factor Xa Inhibitors; Heart Ventricles; Humans; Rivaroxaban; ST Elevation Myocardial Infarction; Treatment Outcome; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Embolism; Factor Xa Inhibitors; Humans; Obesity; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Although several studies have compared the effectiveness and safety of rivaroxaban and apixaban in patients with venous thromboembolism (VTE), direct comparison of these drugs with edoxaban is lacking.. We compared the effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with VTE.. In this retrospective cohort study using a Japanese hospital administrative database, we identified three mutually exclusive groups of patients with VTE beginning treatment with edoxaban, rivaroxaban, or apixaban. Primary effectiveness outcome was recurrent VTE, and principal safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding. Subjects were followed for up to 180 days. Baseline characteristics among groups were balanced using propensity score matching weights.. Three thousand three hundred sixty-nine edoxaban, 1592 rivaroxaban, and 1998 apixaban initiators were identified. There were no significant differences among the three drugs in the prevention of recurrent VTE (adjusted incidence rate ratio [aIRR], 0.77; 95% confidence interval [CI], 0.45-1.30 for edoxaban vs. rivaroxaban; aIRR, 0.92; 95% CI, 0.54-1.56 for edoxaban vs. apixaban; and aIRR, 1.20; 95% CI, 0.69-2.10 for rivaroxaban vs. apixaban), or in the risk of intracranial hemorrhage or gastrointestinal bleeding (aIRR, 1.57, 95% CI, 0.85-2.90 for edoxaban vs. rivaroxaban; aIRR, 1.30, 95% CI, 0.76-2.23 for edoxaban vs. apixaban; and aIRR, 0.83, 95% CI, 0.42-1.64 for rivaroxaban vs. apixaban).. In routine care, edoxaban, rivaroxaban, and apixaban appear to have similar effectiveness and safety in the treatment of VTE.

Topics: Anticoagulants; Cohort Studies; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Venous Thromboembolism

Topics: Anticoagulants; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Polypharmacy; Rivaroxaban; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Polypharmacy; Rivaroxaban; Venous Thromboembolism; Vitamin K

This is the first study examining real-life data of pediatric cancer patients treated with rivaroxaban. Children with thrombocytopenia and high bleeding risk were excluded from previous clinical trials. Data regarding the safety and efficacy of rivaroxaban in pediatric cancer-associated thrombosis are scarce. Our case series included 16 children aged 7.5-17 years. Thrombus resolution rate in our study was comparable to results of previous studies. However, higher rates of thrombotic and bleeding complications were seen in our study as compared to previous reports, especially among patients with relapsed or refractory disease.

Topics: Anticoagulants; Child; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Thrombosis; Treatment Outcome; Venous Thromboembolism

Many thrombotic complications are linked to coronavirus disease 2019 (COVID-19). Antithrombotic treatments are important for prophylaxis against these thrombotic events.. This study was designed to compare enoxaparin and rivaroxaban as prophylactic anticoagulants in moderate cases of COVID-19 in terms of efficacy, safety, and clinical outcomes.. The study involved 124 patients with moderate COVID-19 (pneumonia without hypoxia) divided into two groups. The first group (G1) comprised 66 patients who received enoxaparin subcutaneously at a dose of 0.5 mg/kg every 12 h until discharge from the hospital. The second group (G2) comprised 58 patients who received oral rivaroxaban at a dose of 10 mg once daily until discharge from the hospital. The outcomes evaluated in this study were as follows: intermediate care unit (IMCU) duration, the number of patients transferred from the IMCU to the intensive care unit (ICU), ICU duration, the total length of hospital stay, in-hospital mortality, and thrombotic and bleeding complications.. No significant differences in IMCU duration (p = 0.39), ICU duration (p = 0.96), and total length of hospital stay (p = 0.73) were observed between the two groups. The percentage of patients requiring ICU admission after hospitalization was 21.2% in G1 and 22.4% in G2 (p = 0.87). The mortality rate was 12.1% in G1 and 10.3% in G2 (p = 0.76). The proportion of patients who had thrombotic complications was 9.1% in G1 and 12.1% in G2 (p = 0.59). The incidence of mild bleeding was 3% in G1 and 1.7% in G2 (p = 0.64).. Either enoxaparin or rivaroxaban may be used as thromboprophylaxis agents in managing patients with moderate COVID-19. Either medication has no clear advantage over the other.

Topics: Anticoagulants; COVID-19; Enoxaparin; Humans; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Dabigatran; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism

Symptomatic venous thromboembolism (VTE) following total ankle arthroplasty (TAA) can cause substantial morbidity and mortality. To prevent this complication, surgeons often prescribe postoperative chemoprophylaxis. However, much controversy exists regarding the efficacy of chemoprophylaxis because of the limited studies exploring its use. Furthermore, even less is known about its cost-effectiveness. Therefore, this study sought to determine the cost-effectiveness of commonly prescribed chemoprophylactic agents using a break-even analysis economic model.. The literature was searched, and an online database was used to identify patients who developed a symptomatic VTE after undergoing TAA. Our institutional records were used to estimate the cost of treating a symptomatic VTE, and an online drug database was used to obtain the cost of commonly prescribed chemoprophylactic agents. A break-even analysis was then performed to determine the final break-even rate necessary to make a drug cost-effective.. The low and high rates of symptomatic VTE were determined to be 0.46% and 9.8%. From 2011 to 2021, a total of 3455 patients underwent total ankle arthroplasty. Of these patients, 16 developed a postoperative symptomatic VTE (1.01%). Aspirin 81 mg was cost-effective if the initial symptomatic VTE rates decreased by an absolute risk reduction (ARR) of 0.0003% (NNT = 31 357). Aspirin 325 mg was also cost-effective if the initial rates decreased by an ARR 0.02% (NNT = 5807). Likewise, warfarin (5 mg) was cost-effective at all initial rates with an ARR of 0.02% (NNT = 4480). In contrast, enoxaparin (40 mg) and rivaroxaban (20 mg) were only cost-effective at higher initial symptomatic VTE rates with ARRs of 1.48% (NNT = 68) and 5.36% (NNT = 19). Additional analyses demonstrated that enoxaparin (40 mg) and rivaroxaban (20 mg) become cost-effective when costs of treating a symptomatic VTE are higher than our estimates.. Chemoprophylaxis following TAA can be cost-effective. A tailored approach to VTE prophylaxis with cost-effectiveness in mind may be beneficial to the patient and health system.

Topics: Ankle; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Chemoprevention; Cost-Benefit Analysis; Enoxaparin; Humans; Postoperative Complications; Rivaroxaban; Venous Thromboembolism; Warfarin

Stroke is an independent risk factor for venous thromboembolism (VTE). Although the risk of VTE persists after hospital discharge, information on the utilization of anticoagulants among stroke patients after discharge remains limited.. To evaluate changes in post-discharge thromboprophylaxis among stroke patients between 2006 and 2019.. We conducted a retrospective repeated cross-sectional analysis using a commercial healthcare insurance database in the United States. We included patients aged ≥ 18 years with incident stroke diagnosis and assessed prophylactic use of anticoagulants in the 30 days following hospital discharge including low-molecular-weight heparin (enoxaparin ≤40 mg/day, dalteparin ≤5000 IU/day), unfractionated heparin ≤5000 IU/ twice daily or 3 times a day, apixaban 2.5 mg twice daily, and rivaroxaban 10 mg/day. Patients with atrial fibrillation, VTE, mechanical heart valves, cancer, antiphospholipid antibody syndrome, and users of therapeutic doses of anticoagulants were excluded. We used the Cochrane-Armitage test to assess changes in the use of anticoagulants across the study period.. There was a small increase in the overall use of post-discharge prophylactic anticoagulants among stroke patients between 2006 and 2019 from 0.5% to 1.9%. The use of heparin decreased from 0.5% in 2006 to 0.3% in 2019 (P-value for trend = 0.001). In contrast, the use of apixaban or rivaroxaban increased from 0.1% in 2013 to 1.6% in 2019 (P-value for trend < 0.001). Apixaban was more commonly used than rivaroxaban.. In this population-based study of stroke patients, we found that post-discharge anticoagulant use remains low through 2019. Prophylactic use of heparin or rivaroxaban was relatively low but the use of apixaban increased over the study period. Further research is needed to determine if these agents are safe and effective for VTE prevention in stroke patients.

Topics: Aftercare; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Dalteparin; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Humans; Patient Discharge; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; United States; Venous Thromboembolism

Topics: Colorectal Neoplasms; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Laparoscopy; Rivaroxaban; Venous Thromboembolism

Background A recent randomized trial, the MICHELLE trial, demonstrated improved posthospital outcomes with a 35-day course of prophylactic rivaroxaban for patients hospitalized with COVID-19 at high risk of venous thromboembolism. We explored how often these findings may apply to an unselected clinical population of patients hospitalized with COVID-19. Methods and Results Using a 35-hospital retrospective cohort of patients hospitalized between March 7, 2020, and January 23, 2021, with COVID-19 (MI-COVID19 database), we quantified the percentage of hospitalized patients with COVID-19 who would be eligible for rivaroxaban at discharge per MICHELLE trial criteria and report clinical event rates. The main clinical outcome was derived from the MICHELLE trial and included a composite of symptomatic venous thromboembolism, pulmonary embolus-related death, nonhemorrhagic stroke, and cardiovascular death at 35 days. Multiple sensitivity analyses tested different eligibility and exclusion criteria definitions to determine the effect on eligibility for postdischarge anticoagulation prophylaxis. Of 2016 patients hospitalized with COVID-19 who survived to discharge and did not have another indication for anticoagulation, 25.9% (n=523) would be eligible for postdischarge thromboprophylaxis per the MICHELLE trial criteria (range, 2.9%-39.4% on sensitivity analysis). Of the 416 who had discharge anticoagulant data collected, only 13.2% (55/416) were actually prescribed a new anticoagulant at discharge. Of patients eligible for rivaroxaban per the MICHELLE trial, the composite clinical outcome occurred in 1.2% (6/519); similar outcome rates were 5.7% and 0.63% in the MICHELLE trial's control (no anticoagulation) and intervention (rivaroxaban) groups, respectively. Symptomatic venous thromboembolism events and all-cause mortality were 6.2% (32/519) and 5.66% in the MI-COVID19 and MICHELLE trial control cohorts, respectively. Conclusions Across 35 hospitals in Michigan, ≈1 in 4 patients hospitalized with COVID-19 would qualify for posthospital thromboprophylaxis. With only 13% of patients actually receiving postdischarge prophylaxis, there is a potential opportunity for improvement in care.

Topics: Aftercare; Anticoagulants; COVID-19; Humans; Patient Discharge; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; COVID-19; Enoxaparin; Humans; Rivaroxaban; Venous Thromboembolism

Non-retrieved inferior vena cava filter (IVCF) is associated with some severe complications, such as filter thrombosis. The aim of this retrospective cohort study was to evaluate the outcome of rivaroxaban for the prevention of filter thrombosis in patients with non-retrieved IVCF.. The study based on the VTE registry databases was limited to patients with non-retrieved IVCF treated at Nanjing Drum Tower Hospital from January 2012 to December 2017. Outcomes included filter thrombosis, total bleeding events, death.. A total of 202 patients were enrolled in the study and divided into rivaroxaban group and warfarin group. Mean follow-up period of the two groups was 57.4 ± 20.8 and 62.2 ± 23.0 months, respectively. In risk factors for VTE, transient factors (P = 0.008) and history of VTE (P = 0.028) were statistically different between the two groups. A total of 13 (6.4%) patients developed filter complications, of which 4 (3.5%) and 5 (5.7%) patients in rivaroxaban group and warfarin group developed filter thrombosis, respectively, without significant difference (P = 0.690). The total bleeding events in rivaroxaban group, including major bleeding and clinically relevant and non-major (CRNM) bleeding, were significantly lower than that in warfarin group (P = 0.005). Adjusting for hypertension, transient risk factors, history of VTE and cancer, no differences in the hazard ratio for outcomes were notable.. It is necessary to perform a concomitant anticoagulation in patients with non-retrieved filters. Rivaroxaban can be an alternative anticoagulant option for the prevention of filter thrombosis.

Topics: Anticoagulants; Humans; Retrospective Studies; Rivaroxaban; Thrombosis; Vena Cava Filters; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) is associated with a high risk of morbidity and mortality. However, data on the association between oral anticoagulants and the hazards of VTE complications in Taiwanese patients with VTE is limited. This study aimed to compare the hazards of recurrent VTE, bleeding, and mortality between patients with VTE receiving rivaroxaban, a non-vitamin K antagonist oral anticoagulant (NOAC), and those receiving heparin or low-molecular-weight heparin (LMWH) followed by warfarin. Patients with VTE treated with rivaroxaban, or heparin or LMWH followed by warfarin were enrolled from 2 million random samples from Taiwan's National Health Insurance database between 2013 and 2016. Hazards of recurrent VTE (deep vein thrombosis and pulmonary embolism), major bleeding, and mortality in rivaroxaban and warfarin users were investigated. Survival analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Users of rivaroxaban (183) and warfarin (456) were included in the study. Patients receiving rivaroxaban did not have significantly lower hazards of developing recurrent VTE (HR, 0.72 [CI, 0.37-1.37], P = .31) and mortality (HR, 0.86 [CI, 0.49-1.50], P = .59) than those receiving heparin or LMWH followed by warfarin. In addition, the hazard ratio of major bleeding was not significantly different between the 2 regimens (HR, 1.80 [CI, 0.39-8.29], P = .45). Rivaroxaban was not associated with lower risks of recurrent VTE and mortality and higher hazards of major bleeding than heparin or LMWH followed by warfarin in Taiwanese patients with VTE. Clinicians may tailor oral anticoagulants for VTE patients according to the patient's characteristics, cost-effectiveness and healthcare system policy.

Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

Venous thromboembolic disease (VTD) is currently the second leading cause of death in cancer patients with a prevalence of approximately 20% compared with that of 5% in the entire adult population. Cancer patients are a heterogeneous group with significant differences in the risk of VTD which is, in particular, determined by the type of tumour, its extent, location, and the presence of metastases. Some tumours represent a mean 3- to 5-fold increase in risk, while in others the risk of developing VTD is even several times higher. In comparison with non-cancer patients, those with a tumour are not only at an increased risk of an initial thromboembolic event, but also of its recurrence, regardless of ongoing anticoagulation which is associated with a higher risk of bleeding, particularly in mucosal involvement. Venous thrombosis and its treatment may interfere with the ongoing diagnosis and treatment. In cancer patients, VTD is a frequent incidental finding on imaging studies. Primary thromboprophylaxis (apixaban, rivaroxaban, LMWH) is currently recommended in selected groups of cancer patients who are either hospitalized for acute internal disease or immobilized and have an active malignancy, undergo outpatient systemic chemotherapy for a tumour with a high risk of VTD (a Khorana score of 2) or surgery and are not at high risk of bleeding. DOACs should be administered six months after the initiation of chemotherapy. If there is a risk of drug interactions or mucosal bleeding, LMWHs are recommended. At present, DOACs (apixaban, edoxaban, rivaroxaban) and LMWHs are the first-choice drugs in treating VTD. LMWHs are preferred in mucosal tumours, when there is a high risk of bleeding, in progressive malignancy, concomitant emetogenic therapy, and dyspeptic difficulties. In severe renal insufficiency (CrCl < 15 ml/min), vitamin K antagonists may be of value. Individualized treatment should take into consideration the patients general condition, prognosis, and personal preferences.

Topics: Administration, Oral; Adult; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Infant; Insurance Claim Review; Pulmonary Embolism; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism; Warfarin

Rivaroxaban, a direct oral anticoagulant, is effective against venous thromboembolism (VTE) recurrence without increasing the risk of major bleeding in patients with cancer-associated venous thromboembolism (CAT). However, its clot regression effects are poorly understood. This single-arm, prospective interventional study aimed to investigate the clot regression effects of rivaroxaban in 40 CAT patients, through a contrast-enhanced computed tomography at baseline, 3 weeks, and 3 months of rivaroxaban treatment. The primary endpoint was the clot-regression ratio calculated from the thrombus volumes at 3 weeks and 3 months. Compared with baseline, the total clot volume was significantly reduced at both 3 weeks and 3 months after initiation (p < 0.01). The clot-regression rates were statistically significant with 83.1% (95% confidence interval [CI], 73.8-92.3%) at 3 weeks and 98.7% (95% CI, 97.1-100.2%) at 3 months, with complete resolution in 36.1% and 80.8% of patients at 3 weeks and 3 months, respectively. One patient had recurrent VTE after dose reduction, and seven had non-fatal major bleeding. Therefore, rivaroxaban had a sufficient clot-regression effect against CAT with caution of bleeding complication.

Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Prospective Studies; Rivaroxaban; Thrombosis; Venous Thromboembolism

Obesity and gastric bypass surgery can complicate anticoagulation therapy. In general, patients post-bariatric surgery are considered to be at a moderate risk for deep venous thromboembolism or pulmonary embolism. American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists guidelines recommend chemical prophylaxis with unfractionated heparin or low molecular weight heparin after surgery until the patient is fully mobile, and for those who require chronic anticoagulation, the International Society of Thrombosis and Haemostasis recommend warfarin if body mass index (BMI) is above 40 kg/m

Topics: Anticoagulants; Bariatric Surgery; Enoxaparin; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Obesity; Rivaroxaban; Venous Thromboembolism; Warfarin

Feline arterial thromboembolism (ATE), an often devastating outcome, was recently shown to affect 11.3% of cats with hypertrophic cardiomyopathy over 10 years. Current American College of Veterinary Internal Medicine guidelines recommend the use of clopidogrel in cats at risk for ATE, with addition of a factor Xa inhibitor in very high risk or post-ATE cases. To date, no studies have examined the safety or efficacy of this combined antithrombotic therapy. This retrospective case series aimed to assess the frequency and type of adverse events that occurred in cats prescribed dual clopidogrel and rivaroxaban therapy. Secondary aims were to evaluate indications for dual therapy and clinical outcome.. The study included 32 cats prescribed clopidogrel (18.75 mg PO q24h) and rivaroxaban (2.5 mg PO q24h) on an outpatient basis over a 5-year period.. Cats were prescribed dual therapy for at least one of the following: ATE event (n = 18), presence of an intracardiac thrombi (n = 17) or presence of spontaneous echocardiographic contrast (SEC) (n = 16). Five cats experienced adverse effects that could be attributed to medications, a median of 13 days from initiation (epistaxis, hematemesis, hematochezia or hematuria). No cat required hospitalization as a result of these events. Median survival time from onset of therapy was 257 days (interquartile range [IQR] = 38-497) for all cats, 502 days (IQR = 171-663) for ATE cats, 725 days (IQR = 133-856) for cats with an ATE to two or more limbs and 301 days (IQR = 221-431) for cats with only one limb affected. Recurrence rate of ATE while on dual therapy was 16.7%; no cat newly developed an ATE while on dual therapy.. Dual antithrombotic therapy with clopidogrel and rivaroxaban resulted in a low reported incidence of adverse events. Cats placed on dual therapy for an ATE event experienced a low rate of recurrence and effective thromboprophylaxis was achieved in cats with intracardiac thrombi or SEC.

Topics: Animals; Anticoagulants; Cat Diseases; Cats; Clopidogrel; Humans; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

This study assesses the mortality outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF).. Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer-related death. Secondary outcomes were all-cause mortality, major bleeding, and gastrointestinal (GI) bleeding.. Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer-related death at one year (HR = 0.71, 95% CI = 0.54-0.93) and at the end of follow-ups (HR = 0.79, 95% CI = 0.64-0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all-cause mortality (HR = 0.81, 95% CI = 0.67-0.97), major bleeding (HR = 0.64, 95% CI = 0.47-0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39-0.84) at the end of follow-ups compared with rivaroxaban.. Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer-related death and all-cause mortality.

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Cause of Death; Dabigatran; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Rivaroxaban; Taiwan; Venous Thromboembolism

Kidney transplant recipients(KTRs) are at an increased risk of venous thromboembolism (VTE) and atrial fibrillation(AF). Direct oral anticoagulants (DOACs) have shown important advantages over vitamin K antagonists; however, in KTRs, concerns regarding interactions and use in severe kidney disease may limit their use. This evaluation describes a large UK kidney transplant center's experience of DOACs in KTRs with CrCl > 15 mL/min.. Electronic records were reviewed for all adult KTRs at Manchester University Foundation Trust Hospitals taking DOACs between January 2018 and October 2020 with VTE or AF. The primary outcome was trough and peak DOAC levels within the expected reference ranges and secondary outcomes included bleeding and thrombotic events.. In 31 KTRs taking DOACS, eight patients had a CrCl < 30 mL/min. Overall, 94% (62/66) of DOAC levels were within the recommended ranges. There were no thrombotic events and four bleeding events (two major and two clinically relevant non-major bleeds). The overall bleeding rate was 6.9 per 100 patient-years at risk.. There was no evidence of a significant interaction of apixaban or rivaroxaban with CNIs based on expected DOAC and CNI levels. Their use was found to be safe and effective with no VTE events and bleeding episodes similar to published trial data.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Humans; Kidney Transplantation; Rivaroxaban; Transplant Recipients; Venous Thromboembolism

The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA).. Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis.. We identified 27,736 primary TKA patients who received thromboprophylactic treatment (rivaroxaban (n = 18,846); dalteparin (n = 5,767); dabigatran (n = 1,443); tinzaparin (n = 1,372); and enoxaparin (n = 308)). In the adjusted multivariable analysis and compared with rivaroxaban, treatment with dalteparin (HR 0.68 (95% CI 0.49 to 0.92)) or dabigatran (HR 0.31 (95% CI 0.13 to 0.70)) was associated with a decreased risk of VTE. No statistically significant differences were observed for major bleeding or all-cause mortality. The propensity score matched analysis yielded similar results.. Treatment with dalteparin or dabigatran was associated with a decreased 90-day risk of VTE following primary TKA surgery compared with treatment with rivaroxaban. Cite this article:

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithrombins; Arthroplasty, Replacement, Knee; Dabigatran; Dalteparin; Denmark; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Proportional Hazards Models; Registries; Rivaroxaban; Tinzaparin; Venous Thromboembolism; Young Adult

Direct oral anticoagulants (DOAC) use remains challenging in obese patients treated for Venous-Thrombo-Embolism (VTE) due to the paucity of prospective and dedicated studies.. To assess rivaroxaban and apixaban concentrations at different time-points after intake, in obese patients followed at a thrombosis center and treated for VTE; to define factors associated with DOAC levels outside the on-therapy ranges; and to evaluate bleeding and thrombosis rates during follow-up.. Observational prospective study in two French University hospitals. Apixaban or rivaroxaban concentrations were measured after the first visit, regardless of last intake in obese patients receiving DOAC for VTE. Concentrations were compared to published reference values for non-obese patients. Demographic, clinical, biological and therapeutic data were collected. Univariate and multivariate analyses were performed to identify factors associated to DOAC concentrations outside the on-therapy ranges.. Out of the 146 patients included, 22 (15%) had DOAC concentrations outside the on-therapy ranges, mainly in the rivaroxaban group (n = 17). Age ≤ 63 years, use of rivaroxaban and time since last intake ≤8 h were associated with DOAC concentrations outside the on-therapy ranges, in multivariable analysis. During the median follow-up of 16 months, two (1%) patients receiving apixaban had recurrent VTE. No patient had major bleeding, 11 (8%) patients had minor bleeding.. In this specific prospective bi-centric study dedicated to VTE obese patients, use of DOACs at fixed doses led to concentrations similar to those of non-obese patients in a high proportion of patients, without any effect of the BMI, and with risk-benefit profile comparable to non-obese patients.

Topics: Humans; Middle Aged; Obesity; Pharmaceutical Preparations; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Data on long-term effectiveness and safety of venous thromboembolism (VTE) treatment with rivaroxaban are scarce and not available from randomized clinical trials. To supplement the positive results of phase III VTE treatment trials with rivaroxaban, we used data from the ongoing, prospective, non-interventional DRESDEN NOAC REGISTRY to evaluate long-term management patterns and clinical outcomes. Between December 1st 2011 and September 30th 2020, 812 patients with acute VTE (575 DVT; 237 PE) and rivaroxaban treatment were prospectively followed. During treatment (median rivaroxaban exposure 1.1 years IQR 0.3-5.0 years; median follow-up 6.1 years IQR 4.7-7.8 years) rates of recurrent VTE and ISTH major bleeding were 0.7/100 pt. years (95% CI 0.4-1.1) and 2.1/100 pt. years; 95% CI 1.5-2.8, respectively. Of the 427 patients still taking rivaroxaban at 12 months, 276 and 202 were still taking rivaroxaban at 3 and 5 years, respectively. "Scheduled end of treatment" was the leading discontinuation reason also beyond 12 months. When exposure days were divided by the number of major clinical outcomes (recurrent VTE + other major cardiovascular + ISTH major bleeding), continued rivaroxaban treatment had the longest "exposure per event" period (6398 days/event) compared to patients switching to alternative treatments (4658 days/event) or stopping anticoagulation completely (4337 days/event). Our results confirm low thrombotic and major bleeding rates for long-term VTE treatment with rivaroxaban. Beyond 12 months, scheduled treatment discontinuations still occur. Although 3-5% of patients planned for indefinite rivaroxaban therapy switched to other anticoagulants each year, the overall persistence to rivaroxaban was high.

Topics: Anticoagulants; Humans; Prospective Studies; Registries; Rivaroxaban; Venous Thromboembolism

Cancer-associated venous thromboembolism (CAT) is a common disease or complication which is associated with reduced survival and incurring a substantial health-care cost. Low molecular weight heparin (LMWH) remained the gold standard treatment option available. Direct oral anticoagulants (DOACs) have recently become more popular in the guidelines, they are still few and inconsistent across the current literature. The aim of this study was to evaluate rivaroxaban in treatment of CAT.. In this prospective real-world study, we recruited and followed up patients diagnosed with CAT treated with rivaroxaban or standard of care as a control for 12 months or until death. Baseline characteristics were collected at the study entry. The primary outcomes were recurrent DVT or PE and death within 12 months after treatment initiation. Safety outcomes were composite outcomes of major and minor bleeding.    Results: A total of 80 patients confirm CAT with radiological imaging were recruited; 39 patients were evaluated in the control arm and 41 patients in the rivaroxaban arm. The 12 months cumulative CAT recurrence rate was 46.2% in control and 39% in rivaroxaban (p=0.519). The 12-month death was not a statistically significant difference between both arms (20.5% vs. 31.7%, p=0.255). The cumulative rate of composite safety outcomes was similar in both groups (17.9% vs. 12.2%, p=0.471).. The result of this small but important real-world evidence proofs that rivaroxaban is an effective and safe alternative to the standard of care for CAT in Malaysia's cancer population.

Topics: Anticoagulants; Female; Humans; Malaysia; Male; Middle Aged; Neoplasms; Prospective Studies; Recurrence; Rivaroxaban; Tertiary Healthcare; Treatment Outcome; Venous Thromboembolism

Sickle cell disease (SCD) is a hematological disorder characterized by sickling of red blood cells. Patients are at increased risk of venous thromboembolism. There are no guidelines for the management of venous thromboembolism in sickle cell disease specifically in terms of the anticoagulant of choice.. Here, we report a case of a 30-year-old lady with past medical history of sickle cell disease who came with chest pain and shortness of breath.. We found that she has bilateral pulmonary embolism (PE).. She was started on rivaroxaban.. The patient was followed for 18 months, she did not suffer from recurrence of PE, and she did not develop any complications related to rivaroxaban.. We concluded that rivaroxaban is effective in treating PE in sicklers and also it is safe.

Topics: Adult; Anemia, Sickle Cell; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Reducing the incidence of venous thromboembolism (VTE) following abdominal body contouring surgery remains a top priority for patient safety. There is a lack of consensus regarding the optimal chemoprophylactic agent for postoperative VTE prophylaxis, and the role of oral anticoagulants warrants further investigation.. The aim of this multisurgeon, single-institution study was to determine the safety and efficacy of a 7-day postoperative rivaroxaban regimen for VTE prophylaxis in abdominal body contouring surgery.. A retrospective chart review was performed of all patients who underwent abdominoplasty, circumferential body lift, fleur-de-lis panniculectomy, or circumferential fleur-de-lis panniculectomy at our surgical center from August 2014 to November 2019. A 7-day postoperative course of once-daily 10 mg rivaroxaban, starting on postoperative day 1, was administered to every patient unless there was a contraindication. The 2 primary endpoints were the incidence of VTE and bleeding events.. A total of 600 patients were included in the study. There were no deaths. There were 4 (0.7%) incidents of VTE events: 2 (0.3%) patients suffered pulmonary embolus and 2 (0.3%) patients suffered a lower-extremity deep venous thrombosis. A total of 13 (2.2%) patients suffered complications related to bleeding. Of these, operative intervention for control and evacuation was required in 7 (1.2%) patients.. A 7-day postoperative course of once-daily rivaroxaban for VTE risk reduction in abdominal body contouring surgery is associated with a low incidence of VTE events and a low risk of bleeding complications.

Topics: Anticoagulants; Body Contouring; Humans; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Several studies have shown a reduction in the rate of thromboembolic events with LMWH thromboprophylaxis in patients immobilised in lower limb cast. However, the literature is limited on the use of rivaroxaban in this setting. Therefore the aim of this study was to assess the associated impact of rivaroxaban on the incidence of venous thromboembolism in trauma patients with lower limb cast immobilisation.. Adult patients treated with lower limb cast immobilisation for different types of lower limb injuries were included in this study. One cohort of patients (n = 518) received rivaroxaban thromboprophylaxis. This was compared with a historical cohort (n = 486), who received no rivaroxaban for thromboprophylaxis.. The number of patients developing VTEs in the rivaroxaban group was zero, compared with 6 cases (1.2%) in the nonrivaroxaban group p = 0.013. There were no major or minor bleeding incidences; no wound complications reported in the rivaroxaban group. All the side effects reported in association with rivaroxaban use did not require further intervention.. This study has shown that rivaroxaban is associated with a significant reduction in the risk of VTEs in patients with lower limb cast immobilisation without increasing the risk of bleeding or associated untoward effect. Lower limb immobilisation is high risk factor for VTE per se. However, there is still limited data in the literature to make further recommendations.

Topics: Cohort Studies; Factor Xa Inhibitors; Female; Humans; Incidence; Lower Extremity; Male; Middle Aged; Risk Factors; Risk Reduction Behavior; Rivaroxaban; Venous Thromboembolism

Topics: Atrial Fibrillation; Body Mass Index; Factor Xa Inhibitors; Humans; Meta-Analysis as Topic; Obesity, Morbid; Patient Selection; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

To describe the effect that validation of venous thromboembolism (VTE) coded entries in the health improvement network (THIN) has on incidence rates of VTE among a cohort of rivaroxaban/warfarin users.. Among 36 701 individuals with a first prescription for rivaroxaban/warfarin between 2012 and 2015, we performed a two-step VTE case identification process followed by a two-step case validation process involving manual review of patient records. A valid case required a coded entry for VTE at some point after their first rivaroxaban/warfarin prescription with evidence of referral/hospitalization either as a coded entry or entered as free text. Positive predictive values (PPVs) with 95% confidence intervals (CIs) were calculated using validated cases as the gold standard. Incidence rates were calculated per 1000 person-years with 95% CIs.. We identified 2166 patients with a coded entry of VTE after their initial rivaroxaban/warfarin prescription; incidence rate of 45.31 per 1000 person-years (95% CI: 43.49-47.22). After manual review of patient records including the free text, there were 712 incident VTE cases; incidence rate of 14.90 per 1000 person-years (95% CI: 13.85-16.02). The PPV for coded entries of VTE alone was 32.9%, and the PPV for coded entries of VTE with a coded entry of referral/hospitalization was 39.8%; this increased to 69.6% after manual review of coded clinical entries in patient records.. Among rivaroxaban/warfarin users in THIN, valid VTE case identification requires manual review of patient records including the free text to prevent outcome misclassification and substantial overestimation of VTE incidence rates.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Rivaroxaban; Venous Thromboembolism; Warfarin

Direct factor Xa inhibitors, such as apixaban and rivaroxaban, are widely used for treatment and prevention of venous thromboembolism; however, recent cases of therapeutic failure have been reported. Potential risk factors associated with therapeutic failure such as dose deviations outside of package labeling recommendations, and the use of direct factor Xa-specific inhibitor levels to guide clinical decision making continue to be areas of further investigation. Our study aimed to describe characteristics and dosing regimens in patients on apixaban or rivaroxaban who experienced a new or recurrent thrombosis. We performed a retrospective chart review on 190 patients on either apixaban or rivaroxaban presenting to our institution with new or breakthrough thromboembolism. Evaluation of prescribed anticoagulation regimens compared to package labeling recommendations, direct factor Xa inhibitor-specific anti-Xa levels, anticoagulation interruptions, use of parenteral bridge anticoagulation, final anticoagulation regimen disposition, and thrombosis-associated mortality were recorded. In patients presenting with breakthrough thromboembolism, 78% were on a regimen that matched package labeling recommendations. Anti-Xa levels were documented in 66 patients, the majority of which fell within institutional expected ranges at time of thrombosis. Therapy interruptions immediately prior to thrombosis were observed in 22% of patients and 21% of those patients received parenteral anticoagulation during interruption. Upon discharge, 46% of patients continued the same anticoagulation regimen with no changes. The mortality rate was 6%. In patients who present with new thromboembolism on apixaban or rivaroxaban, a thorough review of risks and benefits should be conducted to mitigate future risk of recurrent thrombosis.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Body Contouring; Humans; Postoperative Period; Rivaroxaban; Venous Thromboembolism

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Ischemic Attack, Transient; Pulmonary Disease, Chronic Obstructive; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Obesity; Registries; Rivaroxaban; United Kingdom; Venous Thromboembolism

Isolated distal deep-vein thrombosis (DVT, infra-popliteal DVT without pulmonary embolism) is a common presentation of venous thromboembolism (VTE), but was an exclusion criterion from the pivotal trials that validated the use of direct oral anticoagulants (DOACs) for VTE management. Using data from the international RIETE registry, we analyzed and compared trends in DOACs prescription between January 2011 and June 2019 in patients with distal vs. proximal DVT. We also assessed DOACs' prescriptions and compared the outcomes (VTE recurrence, bleeding and death) of distal DVT patients treated with DOACs vs. those on vitamin K antagonists (VKAs). 2308 patients with distal DVT and 11,364 patients with proximal DVT were included in the current analysis. DOACs were more frequently prescribed in patients with distal than proximal DVT (25% vs. 16%, p < 0.001). DOACs use increased sharply during the observation period (P < 0.001 for trend). In 2018, 56% of patients with distal DVT received DOACs. Distal DVT patients treated with rivaroxaban or edoxaban received the dose recommended for VTE management in most (> 85%) cases. Patients treated with apixaban were older, more likely to have underlying conditions than patients treated with rivaroxaban and, in most cases (> 75%), did not receive the recommended 1-week loading dose for acute VTE management. Outcomes between distal DVT patients treated with VKAs or DOACs appeared to be similar. In patients with distal DVT, DOACs have become the most common anticoagulant regimen. Specific trials are needed to determine the optimal DOACs dose regimen for treatment of distal DVT.

Topics: Administration, Oral; Anticoagulants; Humans; Registries; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Direct oral anticoagulant (DOAC) starter packs are designed for unique treatment dosing for acute venous thromboembolism (VTE). Inappropriate use of 30-day DOAC starter packs in patients with atrial fibrillation (AF) may increase the risk for bleeding events given higher dosing in the first 1-3 weeks of treatment. A retrospective analysis of medical and outpatient pharmacy claims data from 2015 to 2018 in Optum's De-identified Clinformatics® Data Mart was performed. Patients greater than 18 years of age with AF and a new prescription of apixaban or rivaroxaban were included. Patients with an acute VTE were excluded. The main outcome of interest was adverse events (emergency department [ED] visits, hospitalizations, and deaths within 90 days after prescription fill date) associated with inappropriate DOAC starter pack prescription. A total of 90,950 DOAC-treated patients with AF were identified. The mean age was 74.5 years (SD 10.0) and 42,717 (47.0%) were female. Inappropriate starter packs were used by 117 (0.1%) patients, who were younger than non-starter pack patients (71.3 years vs. 74.5 years). Patients who received an inappropriate DOAC prescription were more likely to identify as Black (12.0% vs. 8.8%). Rates of ED visits, hospitalizations, and deaths overall were numerically lower in patients with starter pack compared to non-starter pack DOAC prescriptions. In contrast, rates of ED visits and hospitalizations related to significant bleeding were numerically higher in patients with starter pack compared to non-starter pack DOAC prescriptions. Among patients with AF but no VTE, those who received an inappropriate DOAC starter pack had numerically higher rates of severe bleeding leading to ED visits and hospitalizations compared to those prescribed an appropriate non-starter pack DOAC anticoagulant.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Drug-Related Side Effects and Adverse Reactions; Female; Hemorrhage; Humans; Prescriptions; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Developing Countries; Factor Xa Inhibitors; Humans; Length of Stay; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

To determine the effect and safety of sequential treatment with the low-molecular-weight heparin dalteparin and the direct oral anticoagulants rivaroxaban in patients with cancer- associated venous thromboembolism (VTE).. Observational study.. Department of Oncology, the Second Affiliated Hospital of Soochow University, between January 2017 and September 2019.. Patients with active cancer, diagnosed with VTE and who received sequential treatment with dalteparin and rivaroxaban, were retrospectively reviewed. Logistic regression analysis was used to identify risk factors associated with VTE recurrence.. Ninety-nine patients with active cancer were enrolled in the study. The median delteparin treatment time was nine days (5-20 days), and 2.8 months (1-6 months) for rivaroxaban. Sixty (60.6%) patients had eliminated VTE, and 39 (39.4%) had persistent VTE, but with relieved symptoms. No major bleeding was observed. Eleven (11.1%) patients had minor bleeding, including melena (5.1%), hematuria (3.0%), vaginal bleeding (1.0%), gingival bleeding (1.0%), and subcutaneous hemorrhage (1.0%). During the 6 months follow-up period, one (1.0%) developed pulmonary embolism, and seven (7.1%) experienced recurrent VTE. Univariate logistic regression analysis showed that bleeding occurrence and anticoagulant treatment duration were the two significant factors affecting VTE recurrence (p<0.05).. Maintenance of rivaroxaban after initial dalteparin treatment could effectively reduce the risk of VTE recurrence and was well tolerated by patients with cancer-associated VTE. However, in the clinical practice, the treatment duration is often insufficient, so it is essential to follow-up these patients to ensure sufficient treatment time. Key Words: Venous thromboembolism, Low-molecular-weight heparins, Directly oral anticoagulants, Cancer.

Topics: Anticoagulants; Dalteparin; Female; Humans; Neoplasms; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes.. To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE).. This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up.. Use of ASA concomitant with DOAC therapy.. Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death.. Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02).. Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Dabigatran; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Pyrazoles; Pyridines; Pyridones; Registries; Rivaroxaban; Thiazoles; Venous Thromboembolism

To assess the efficacy and safety of once-daily 10 mg rivaroxaban for venous thromboembolism prophylaxis after ClosureFast radiofrequency ablation (RFA) of saphenous veins.. The medical records of patients, who had a Caprini score of ≥3, underwent RFA, received prophylactic rivaroxaban for five days, and completed follow up at one month were reviewed for efficacy (a combination of endovenous heat-induced thrombosis [EHIT] grade of 2-4, any symptomatic or asymptomatic deep vein thrombosis [DVT], and symptomatic pulmonary embolism [PE]) and safety (a combination of major and clinically relevant non-major [CRNM] bleeding) outcomes.. The results of RFA for 248 great saphenous and 24 small saphenous veins with the concomitant miniphlebectomy (63.8%) and sclerotherapy (16.5%) were analyzed. The primary efficacy outcome occurred in 5 of 218 (2.3%; 95%CI, 1.0-5.3%) patients: three EHITs and two symptomatic DVTs. The CRNM bleeding was reported in two patients (0.9%; 95% CI, 0.2-3.3%). No difference was observed in comparison with 79 similar patients who received 40 mg of subcutaneous enoxaparin during the same time period.. Once-daily 10 mg rivaroxaban is suitable for VTE prophylaxis after RFA of saphenous veins.

Topics: Catheter Ablation; Humans; Radiofrequency Ablation; Rivaroxaban; Saphenous Vein; Sclerotherapy; Treatment Outcome; Varicose Veins; Venous Thromboembolism

Rivaroxaban, enoxaparin, and aspirin are commonly used medications for thromboprophylaxis following lower extremity joint arthroplasty or revision. Previous research has demonstrated efficacy in preventing venous thromboembolism with each medication, however, the comparative risk of bleeding between them remains poorly understood. The aim of this study was to compare the odds of bleeding between rivaroxaban, enoxaparin, and aspirin following lower extremity joint arthroplasty or revision.. This is a 3-year retrospective cohort study.. Data were obtained from 148 facilities across 55 states and territories of the United States.. This study included 85,938 patients who underwent hip or knee arthroplasty or revision.. Patients received enoxaparin, rivaroxaban, or aspirin as monotherapy for thromboprophylaxis.. The primary outcome was all bleeding, classified as major or minor bleeding, occurring in the 40 days following surgery. The secondary outcome was venous thromboembolism.. Among 85,938 patients, 10,465 received rivaroxaban, 14,047 received enoxaparin, and 61,426 received aspirin. Bleeding occurred in 126 (1.20%) patients with rivaroxaban, 253 (1.80%) with enoxaparin, and 611 (0.99%) with aspirin. There was a significant increase in odds of bleeding in the enoxaparin compared to aspirin group odds ratio (OR) 1.18, 95% confidence interval (CI) 1.01-1.38, p = 0.042), and a trend toward increased odds of bleeding in rivaroxaban compared to aspirin group (OR 1.21, 95% CI 0.99-1.47, p = 0.058) and rivaroxaban compared to enoxaparin (OR 1.03, 95% CI 0.82-1.28, p = 0.827). Odds of venous thromboembolism were not statistically significant between all three study medications.. Among rivaroxaban, enoxaparin, and aspirin used for thromboprophylaxis in knee and hip arthroplasty or revision, aspirin had significantly decreased odds of bleeding complications compared to enoxaparin. Although not statistically significant, aspirin also had a trend toward decreased odds of bleeding complications compared to rivaroxaban. Our study results suggest that aspirin is a safer alternative for use in postoperative thromboprophylaxis following lower extremity joint arthroplasty or revision.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Enoxaparin; Humans; Postoperative Hemorrhage; Reoperation; Retrospective Studies; Risk Assessment; Rivaroxaban; Venous Thromboembolism

Data describing treatment patterns of patients with venous thromboembolism (VTE) patients in Scandinavia are scarce. This study sought to address this scarcity by describing demographic and clinical characteristics, trends in the use of oral anticoagulants (OACs), and treatment patterns in patients treated for VTE in Norway between 2013 and 2017.. Using data from Norway's nationwide registries, a cohort study included patients newly (after 2008) treated OACs who were diagnosed with VTE between January 2013 and December 2017 and were dispensed an OAC (warfarin, apixaban, rivaroxaban, dabigatran, or edoxaban) within 30 days. Patient characteristics and the percentage of patients with VTE who initiated treatment with each OAC for each calendar year were reported. Initial therapy persistence was assessed using Kaplan-Meier curves and compared between the OAC groups using the log-rank test.. The comorbidity burden was similar between patients taking warfarin and those taking apixaban but lower among patients taking rivaroxaban. Direct oral anticoagulant (DOAC) use increased from 33.2% to 93.6% during the study period, whereas warfarin use decreased. Persistence was higher in the apixaban cohort compared with the warfarin cohort, with the difference mostly apparent after 6 months, whereas persistence was similar between the patients taking rivaroxaban and those taking warfarin.. Between 2013 and 2017, DOAC use among patients with VTEs increased markedly in Norway, whereas the use of warfarin decreased. Patients taking apixaban had higher persistence compared with those taking warfarin, whereas patients taking warfarin and those taking rivaroxaban had similar persistence. Further studies with longer follow-up are required to examine the use of extended OAC treatment for VTE.

Topics: Administration, Oral; Anticoagulants; Cohort Studies; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Dabigatran; Female; Humans; Incidence; Pyrazoles; Pyridones; Rivaroxaban; Uterine Hemorrhage; Venous Thromboembolism

Venous thromboembolism in children is rare, but the incidence has increased sharply during the last years. The standard of care for treating this disease consists of warfarin, unfractionated heparin, low-molecular-weight heparins and fondaparinux. Lately, the usage of rivaroxaban (direct oral anticoagulant) was officially approved. According to a recent study, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased risk of bleeding. The usage of direct oral anticoagulants could overcome the limitation of currently used care (mainly the necessity of regular laboratory monitoring and parenteral application) while providing similar efficacy and safety to treat venous thromboembolism in children.

Topics: Anticoagulants; Child; Heparin; Humans; Rivaroxaban; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) management increasingly involves anticoagulation with direct oral anticoagulants (DOACs). Few studies have used competing-risks analyses to ascertain the mortality-adjusted hemorrhage and recurrent VTE (rVTE) risk of individual DOACs. Furthermore, hemorrhage risk factors in patients treated with apixaban remain underexplored.. Patients diagnosed with VTE receiving anticoagulation were identified from the Optum Clinformatics Data Mart (2003-2019). Study endpoints included readmissions for intracranial hemorrhage (ICH), non-intracranial hemorrhage (non-ICH hemorrhage), and rVTE. Coarsened exact matching was used to balance baseline clinical characteristics. Complication incidence was evaluated using a competing-risks framework. We additionally modeled hemorrhage risk in apixaban-treated patients.. Overall, 225,559 patients were included, of whom 34,201 received apixaban and 46,007 received rivaroxaban. Compared to rivaroxaban, apixaban was associated with decreased non-ICH hemorrhage (sHR = 0.560, 95%CI = 0.423-0.741), but not ICH, and rVTE (sHR = 0.802, 95%CI = 0.651-0.988) risk. This was primarily in emergent readmissions (sHR[emergent hemorrhage] = 0.515, 95%CI = 0.372-0.711; sHR[emergent rVTE] = 0.636, 95%CI = 0.488-0.830). Contributors to emergent hemorrhage in apixaban-treated patients include older age (sHR = 1.025, 95%CI = 1.011-1.039), female sex (sHR = 1.662, 95%CI = 1.252-2.207), prior prescription antiplatelet therapy (sHR = 1.591, 95%CI = 1.130-2.241), and complicated hypertension (sHR = 1.936, 95%CI = 1.134-3.307). Patients anticipated to be "high-risk" experienced elevated ICH (sHR = 3.396, 95%CI = 1.375-8.388) and non-ICH hemorrhage (sHR = 3.683, 95%CI = 2.957-4.588) incidence.. In patients with VTE receiving anticoagulation, apixaban was associated with reduced non-ICH hemorrhage and rVTE risk, compared to rivaroxaban. Risk reduction was restricted to emergent readmissions. We present a risk-stratification approach to predict hemorrhage in patients receiving apixaban, potentially guiding future clinical decision-making.

Topics: Administration, Oral; Aged; Anticoagulants; Female; Hemorrhage; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism

Given high recurrence risk after venous thromboembolism (VTE), guidelines recommend extended dose rivaroxaban (10 mg OD) or apixaban (2.5 mg BID) to be considered after 6 months of initial treatment. This study aimed to provide insight into clinical practice regarding the use of extended preventive treatment and to describe duration of the initial treatment. Linkage of nationwide health registers identified all in- and outpatients with VTE from April 2017 through 2018. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated adjusting for other VTE-related factors. The study included 6030 patients with VTE. Among rivaroxaban users, 2.2% (n = 113) received the extended 10-mg dose after mean 9.4 (SD 3.1) months of standard treatment. For apixaban, 4.7% (n = 40) received extended 2.5-mg dose after mean 8.0 months (SD 3.9). After adjustments, incident pulmonary embolism (HR 1.81 95% CI 1.12;2.91) and trauma/fracture (HR 1.42 95% CI 0.46;4.43) were associated with switching to extended dose, whereas patients with unprovoked VTE were less likely to receive the extended dose (HR 0.68 95% CI 0.30;1.55). Less than 3% of patients with incident VTE received extended treatment after initial standard treatment. Even though international guidelines suggest that the risk-benefit balance is in favour of extended VTE treatment, this was yet to be translated into clinical practice as of 2018. Studies using contemporary data are warranted to investigate routine clinical practice of extended treatment for VTE recurrence.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Rivaroxaban has been investigated in the EINSTEIN-Jr program for the treatment of acute venous thromboembolism (VTE) in children aged 0 to 18 years and in the UNIVERSE program for thromboprophylaxis in children aged 2 to 8 years with congenital heart disease after Fontan-procedure. Physiologically-based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modeling were used throughout the pediatric development of rivaroxaban according to the learn-and-confirm paradigm. The development strategy was to match pediatric drug exposures to adult exposure proven to be safe and efficacious. In this analysis, a refined pediatric PopPK model for rivaroxaban based on integrated EINSTEIN-Jr data and interim PK data from part A of the UNIVERSE phase III study was developed and the influence of potential covariates and intrinsic factors on rivaroxaban exposure was assessed. The model adequately described the observed pediatric PK data. PK parameters and exposure metrics estimated by the PopPK model were compared to the predictions from a previously published pediatric PBPK model for rivaroxaban. Ninety-one percent of the individual post hoc clearance estimates were found within the 5th to 95th percentile of the PBPK model predictions. In patients below 2 years of age, however, clearance was underpredicted by the PBPK model. The iterative and integrative use of PBPK and PopPK modeling and simulation played a major role in the establishment of the bodyweight-adjusted rivaroxaban dosing regimen that was ultimately confirmed to be a safe and efficacious dosing regimen for children aged 0 to 18 years with acute VTE in the EINSTEIN-Jr phase III study.

Topics: Adolescent; Child; Child, Preschool; Computer Simulation; Factor Xa Inhibitors; Female; Fontan Procedure; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Models, Biological; Prospective Studies; Rivaroxaban; Venous Thromboembolism

Thrombosis is the most common adverse event in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Little is known about the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with myeloproliferative neoplasms. We sought to evaluate the efficacy and safety of NOAC in a cohort of patients with PV and ET, who experienced venous thromboembolism (VTE). We enrolled 48 consecutive patients with PV (70.8%) and ET [median age 67.0 (interquartile range, 58.5-72.0) years], who experienced VTE. Patients received apixaban (39.6%), rivaroxaban (33.3%), or dabigatran (27.1%). During a median follow-up of 30 (interquartile range, 20.5-41.5) months, recurrent thrombotic events and bleeding were recorded. Four thrombotic events (3.3 per 100 patient-years) were reported. Three deep vein thrombosis episodes (2.5 per 100 patient-years) were experienced by 2 patients with PV, who received apixaban (5 mg bid) and dabigatran (150 mg bid), and 1 patient with ET, who received dabigatran (150 mg bid). One ischemic stroke occurred in a patient with PV on rivaroxaban (20 mg/d). There was 1 major bleeding (0.8 per 100 patient-years) in a patient with ET on dabigatran (150 mg bid) and 3 clinically relevant nonmajor bleeding (2.5 per 100 patient-years): 2 on rivaroxaban (20 mg/d) and 1 on apixaban (5 mg bid). We did not observe significant differences related to the type of NOAC. Three deaths (2.5 per 100 patient-years) unrelated to either VTE or bleeding were recorded. This study shows that NOACs may be effective and safe as secondary prevention of VTE in patients with myeloproliferative neoplasms.

Topics: Administration, Oral; Aged; Antithrombins; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Polycythemia Vera; Pyrazoles; Pyridones; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Thrombocythemia, Essential; Time Factors; Treatment Outcome; Venous Thromboembolism

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Neoplasms; Patient Reported Outcome Measures; Rivaroxaban; Venous Thromboembolism; Warfarin

Topics: Arthroplasty, Replacement, Hip; Humans; Lower Extremity; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Direct oral anticoagulants (DOACs) present a favorable alternative to warfarin based on the decreased burden of monitoring and fewer drug and food interactions. Although studied in the general population, limited clinical data justifying efficacy in patients weighing ≥120 kg present concern for using DOACs in this specific population.. The purpose was to identify if a difference exists in incidence of recurrent thromboembolic events in patients receiving a DOAC for the indication of venous thromboembolism (VTE) weighing ≥120 kg compared to patients weighing <120 kg.. A retrospective database analysis was conducted with patients on apixaban, dabigatran, or rivaroxaban for treatment of VTE from the Veterans Integrated Service Network 8 between January 2012 and June 2017. The primary outcome was incidence of recurrent VTEs while on anticoagulation. Fisher's exact tests were used to evaluate difference in VTEs between the groups.. There were 133 patients weighing ≥120 kg and 1063 patients weighing <120 kg identified within the 5-year time frame that met inclusion criteria. Although no statistically significant difference was found in incidence of recurrent VTEs between study groups (0.8% vs 1.1%; odds ratio: 0.66; 95% confidence interval: 0.09-5.14;. This study found no difference in VTE recurrence in patients weighing ≥120 kg compared to patients <120 kg with few events in either group. Although promising, additional studies are needed to confirm these findings.

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Incidence; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Aged; Autoantibodies; Cross Reactions; Female; Fondaparinux; Heparin; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Rivaroxaban; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism

Patients with cystic fibrosis (CF) and venous thromboembolism (VTE) pose therapeutic challenges including potential drug interactions between CF-related therapies and anticoagulants. Despite these challenges, there are no recommendations for VTE management specific to patients with CF. Our objective was to describe VTE treatment practices among Cystic Fibrosis Foundation (CFF)-accredited care centers and affiliate programs in the United States.. An online survey was distributed to CF center directors. The survey included questions regarding centers' demographics and posed a series of hypothetical clinical scenarios to gather centers' VTE treatment practices including choice of anticoagulant, dosing practices, duration decisions, and monitoring efforts. Descriptive statistics were utilized to summarize the survey results.. The survey response rate was 56.3%. Most centers reported treating zero to five VTE episodes per year. The following anticoagulants were used most often for VTE treatment: low-molecular-weight heparin (LMWH) (73.2%), apixaban (36.6%), warfarin (35.2%), rivaroxaban (33.8%), and unfractionated heparin (18.3%). On a scale of 0 to 100, the median confidence level in managing anticoagulant therapy was 50. Many centers expressed a desire for a CF-specific VTE treatment guideline. The most commonly cited challenging clinical situations were managing anticoagulant therapy complications (26.5%) and drug-drug interactions (21.3%). For common VTE scenarios, pediatric patients were most often treated with LMWH and warfarin, whereas adult patients were more often treated with apixaban or rivaroxaban.. Survey results indicated CF care centers find managing VTE in patients with CF challenging and indicated that a CF-specific VTE treatment guideline would be helpful.

Topics: Adult; Anticoagulants; Child; Cystic Fibrosis; Heparin; Humans; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Rivaroxaban; Surveys and Questionnaires; Venous Thromboembolism; Warfarin

Recent guidelines recommend direct acting oral anticoagulants (DOAC) over vitamin-k antagonist (VKA) for acute venous thromboembolism (VTE). Non-adherence to anticoagulation has been associated with increased frequency of VTE or stroke. This study evaluated 90 day persistence among patients prescribed rivaroxaban or warfarin for the treatment of acute VTE at an academic safety net hospital. We conducted a single center, retrospective cohort study of 314 consecutive patients newly prescribed rivaroxaban or warfarin for acute VTE between January 2016 and July 2017. Primary outcome was 90 day persistence, and secondary outcomes included 90 day readmission and/or ED visit, time to 90 m day readmission and/or ED visits, and attendance of direct oral anticoagulant education class. Of 314 patients, 78 were prescribed warfarin and 236 rivaroxaban. Patients had a mean age of 52 years, 62% were men, and 96% were diagnosed with deep vein thrombosis and/or pulmonary embolism. Persistence at 90 days was 52.6% among patients prescribed warfarin compared to 45.3% for patients prescribed rivaroxaban (p = 0.2678). Persistencewas associated with decreased 90 day hospital or ED readmission. Among patients prescribed rivaroxaban, attending a pharmacist led educational class was associated with a 2.5 fold increase in persistence (p < 0.0001). Among patients with new onset venous thromboembolism, 90 day persistence with anticoagulation was similarly low with either rivaroxaban or warfarin therapy. Participation in a pharmacist led DOAC class was associated with a 2.5-fold increase in persistence on rivaroxaban.

Topics: Academic Medical Centers; Adult; Aged; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Male; Medication Adherence; Middle Aged; Patient Discharge; Retrospective Studies; Rivaroxaban; Safety-net Providers; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Child; Humans; Pediatricians; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Humans; Neoplasms; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients.. In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB).. APS patients were followed for a median time of 51 (interquartile range 43-63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54-10.28,. During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

Topics: Adult; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Vitamin K

Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin.. The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality.. During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%).. In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.

Topics: Aged; Dalteparin; Factor Xa Inhibitors; Female; Genital Neoplasms, Female; Hemorrhage; Humans; Middle Aged; Proportional Hazards Models; Republic of Korea; Rivaroxaban; Venous Thromboembolism

Prevention of thromboembolic disease requires patients' adherence to the extended thromboprophylaxis scheme. Oral anticoagulants are expected to improve adherence as a result of their route of administration; however, this assumption is yet to be confirmed. The purpose of this study was to assess the impact of the route of administration and dosage regimen on the compliance to the prescription.. This prospective cohort study included hip and knee arthroplasty patients who received pharmacological extended thromboprophylaxis with one daily injection, one daily oral tablet, or two daily oral tablets. A telephonic questionnaire was applied 35 days after the day of the surgery. Patients who omitted one or more doses of medication during the follow-up period were classified as "non-adherent." Differences of adherence rates were assessed.. Five hundred and twenty patients were included: 153 received Apixaban (oral, twice a day), 155 Enoxaparin (injectable, once a day), and 212 Rivaroxaban (oral, once a day). Patients receiving oral once a day medication was more compliant compared with those who received an oral medication twice a day. Non-adherence rates were 3.2 and 9.2%, respectively (p = 0.033). No significant differences (p = 0.360) were found between oral once a day and injectable once a day medication.. The number of daily doses prescribed was related to adherence to extended chemical prophylaxis, while the route of administration did not seem to have a significant impact. Strategies to promote outpatient compliance must be implemented, especially when regimes including more than one daily dose are prescribed.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dose-Response Relationship, Drug; Drug Administration Routes; Enoxaparin; Female; Hip Fractures; Humans; Injections, Subcutaneous; Male; Medication Adherence; Middle Aged; Osteoarthritis; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Young Adult

Topics: Anticoagulants; Dalteparin; Female; Humans; Neoplasm Recurrence, Local; Rivaroxaban; Venous Thromboembolism

Topics: Anterior Cruciate Ligament Reconstruction; Anticoagulants; Arthroscopy; Double-Blind Method; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Venous Thromboembolism

Topics: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Anticoagulants; Arthroscopy; Double-Blind Method; Heparin, Low-Molecular-Weight; Humans; Rivaroxaban; Venous Thromboembolism

Studies on the use of direct oral anticoagulants (DOACs) in obese patients are limited. Current guidelines advise against DOAC use in patients with a body weight more than 120 kg or body mass index higher than 40 kg/m. Retrospective matched cohort study.. Integrated delivery system of 40 academic, community, and specialty hospitals.. A total of 1840 adults with a primary admission diagnosis of acute VTE who received a DOAC (apixaban, dabigatran, or rivaroxaban [632 patients] or warfarin [1208 patients]) while hospitalized between January 1, 2011, and October 1, 2015, and who had a body weight more than 100 kg and less than 300 kg, were included. Patients in the warfarin group were matched in a 2:1 ratio to patients who received a DOAC based on history of VTE, chronic kidney disease, race, and age.. The primary outcome was recurrence of VTE within 12 months of the index admission date. Secondary outcomes included occurrence of pulmonary embolism (PE) and deep vein thrombosis (DVT) events separately within the study time frame, as well as bleeding within 12 months of the index admission date. No significant difference in the recurrence of VTE was observed between patients who received a DOAC compared with those who received warfarin (6.5% vs 6.4%, p=0.93). Likewise, no significant differences in the occurrence of PE and DVT were seen between the DOAC- and warfarin-treated patients (3.7% vs 3.8%, p=0.94, and 3% vs 3.5%, p=0.56, respectively). Bleeding occurred in 1.7% and 1.2% of patients in the DOAC and warfarin groups, respectively (p=0.31).. To our knowledge, this is the largest clinical study to date showing that patients with obesity can be treated effectively and safely with a DOAC compared with warfarin for acute VTE. Thus DOACs should be considered a reasonable alternative to warfarin for treatment of acute VTE in obese patients.

Topics: Administration, Oral; Aged; Anticoagulants; Cohort Studies; Dabigatran; Female; Humans; Male; Middle Aged; Obesity, Morbid; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically.. The sensitivity of the rivaroxaban, apixaban, and edoxaban in the STA-Liquid Anti-FXa assay were compared, and the anti-FXa plasma concentrations were measured for PK assessments. Nonlinear mixed-effects modeling was used to assess population PK in 329 patients with nonvalvular atrial fibrillation or venous thromboembolism. Patients were followed up for an average of 3.6 years.. Sensitivity was similar among the three drugs in this assay, which could directly compare plasma concentrations instead of anti-FXa activities. Overall exposure was greatest in 5 mg BID apixaban relative to other drugs (p < 0.001). The geometric mean AUC for the 0 to 24-h interval was 4550 ng h/mL for apixaban, 2710 ng h/mL for 15 mg QD rivaroxaban, and 1290 ng h/mL for 60 mg QD edoxaban. The PKs of 2.5 mg BID apixaban or 15 mg QD rivaroxaban were associated with hemorrhagic events.. Apixaban was associated with greater exposure, higher trough concentrations in plasma compared with rivaroxaban or edoxaban. Furthermore, a higher plasma concentration may partially predict hemorrhagic events.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation Tests; Chromatography, Liquid; Factor Xa; Factor Xa Inhibitors; Female; Humans; Male; Prospective Studies; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Tandem Mass Spectrometry; Thiazoles; Venous Thromboembolism

Venous thromboembolism is a common complication among cancer patients with an estimated risk of 20%. American Society of Clinical Oncology guidelines recommend direct oral anticoagulants for long-term anticoagulation but caution the use of direct oral anticoagulants because of drug-drug interactions with antineoplastic therapies. The clinical impact of these drug-drug interactions is yet to be studied in clinical trials. This study aims to evaluate the effect of the drug-drug interactions on venous thromboembolism recurrence and bleeding.. This is a retrospective cohort study that included cancer patients with venous thromboembolism receiving apixaban or rivaroxaban with antineoplastic therapy. The impact of the drug-drug interaction was determined by its effect on the rates of venous thromboembolism recurrence and bleeding in patients with a drug-drug interaction compared to patients with no drug-drug interaction.. The primary composite endpoint of venous thromboembolism recurrence and bleeding events occurred in 65% versus 62% of patients in drug-drug interaction and non-drug-drug interaction groups accordingly. There was a higher rate of venous thromboembolism recurrence and minor bleeding events with anti-mitotic microtubule inhibitors and a higher rate of minor bleeding events with hormonal therapy and alkylating agents. Among the drug-drug interaction group, there were no major bleeding events reported with mild drug-drug interactions when compared to moderate-to-severe drug-drug interactions. There was no difference in time to venous thromboembolism recurrence between rivaroxaban and apixaban.. Due to small sample size, our study results could not confirm a higher risk of bleeding or venous thromboembolism recurrence with the drug-drug interactions. Further prospective study is warranted, but clinicians should be aware of these drug-drug interactions and identify them using available literature.

Topics: Aged; Anticoagulants; Drug Interactions; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Although rivaroxaban has recently become widely used for thrombosis treatment, it is difficult for clinicians to make clinical decisions in critical situations, such as emergent surgery or interventions, because a specific anti-Xa assay is not available in many laboratories. This study assessed the relationships between rivaroxaban-specific anti-factor Xa activity (AXA) and unfractionated heparin (UFH)-specific AXA and determined the cutoff level for UFH-specific AXA in critical situations for patients undergoing rivaroxaban therapy.. Thirty-eight blood samples were collected from patients with cancer-associated thrombosis receiving rivaroxaban therapy. All samples were assessed using both rivaroxaban-specific and UFH-specific anti-Xa assays. Routine coagulation studies, including prothrombin time (PT) and activated partial thromboplastin time, were also conducted on the samples.. A positive dose-dependent correlation between rivaroxaban-specific and UFH-specific AXA was evident (R = 0.97; P < .0001). Rivaroxaban-specific AXA was also positively correlated with PT (R = 0.95; P < .0001) but only weakly with activated partial thromboplastin time (R = 0.67; P < .0001). Patients with plasma rivaroxaban concentrations <100 ng/mL were found to have UFH-specific AXA <1.41 IU/mL and PT <17.3 seconds, with sensitivities of 100% and 93.3% and specificities of 87.0% and 95.7%, respectively.. Our study demonstrates that UFH-calibrated AXA correlates strongly with plasma rivaroxaban concentration. This assay appears to be sensitive to the presence of rivaroxaban, which may be advantageous in the setting of assessing drug levels for critical events. These findings suggest that if a rivaroxaban-specific anti-Xa assay is unavailable, the chromogenic anti-Xa assay for UFH may be useful to assess the anticoagulant effects of rivaroxaban.

Topics: Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Clinical Decision-Making; Drug Monitoring; Factor Xa Inhibitors; Female; Heparin; Humans; Male; Middle Aged; Neoplasms; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Rivaroxaban; Venous Thromboembolism

Since 2012 four direct oral anticoagulants (DOAC) have been approved by the US Food and Drug Administration (FDA) for treatment of acute venous thromboembolism (VTE). Clinical trials comparing DOACs to warfarin included more than 13,500 patients. However, included patients were all age 39 years or older. We sought to describe real-world use of DOACs among young adults with acute VTE. Multi-center retrospective case series of young adult patients (age 18-40 years) at two large academic medical centers who initiated any DOAC for VTE therapy in 2015 or 2016. Thrombotic and bleeding events as well as off-label drug use were described using summary statistics. Fifty-seven patients were identified (63.2% female). One of the 57 patients (1.8%) had a thromboembolic event. Seven of the 57 patients (12.3%) experienced a bleeding event, one categorized as a major bleed and six being categorized as clinically relevant non-major bleeding. One of the ten (10%) patients receiving apixaban was not initiated on the FDA-recommended 10 mg twice daily for the first 7 days. Seven of the 47 (14.9%) patients receiving rivaroxaban were not initiated on the FDA-recommended 15 mg twice daily dosing for the first 21 days. Bleeding occurred in approximately 14% of young adult patients treated with DOAC therapy. However, only one patient had their DOAC discontinued due to a major bleeding event. Recurrence of DVT while on DOAC therapy was rare.

Topics: Acute Disease; Adult; Age Factors; Dose-Response Relationship, Drug; Electronic Health Records; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Off-Label Use; Practice Guidelines as Topic; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; United States; Venous Thromboembolism

The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.. In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.. A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.. These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Topics: Administration, Oral; Adult; Age Distribution; Aged; Anticoagulants; Asia; Comorbidity; Cross-Sectional Studies; Dabigatran; Diabetes Mellitus; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension; Latin America; Male; Middle Aged; Middle East; Neoplasms; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries

Background The risk of venous thromboembolism following major orthopaedic surgery is among the highest for all surgical specialties. Our hospital guidelines for thromboprophylaxis following elective primary total hip or knee replacement are based on American College of Chest Physicians guidance. The most recent change to local guidelines was the introduction of the extended aspirin regimen as standard thromboprophylaxis. Objective To establish the appropriateness of this regimen by comparing venous thromboembolism rates in patients receiving extended aspirin to previous regimens. Setting The largest dedicated orthopaedic hospital in Ireland. Methods This was a retrospective cohort study. Data were collected from patient record software. All eligible patients undergoing primary total hip or knee replacement between 1st January 2010 and 30th June 2016 were included. Main outcome measure Venous thromboembolism up to 6 months post-operatively. Results Of the 6548 participants (55.3% female, mean age 65.4 years (± 11.8 years, 55.8% underwent total hip replacement), venous thromboembolism occurred in 65 (0.99%). Venous thromboembolism rate in both the inpatient enoxaparin group (n = 961) and extended aspirin group (n = 3460) was 1.04% and was 0.66% in the modified rivaroxaban group (n = 1212). Non-inferiority analysis showed the extended aspirin regimen to be equivalent to the modified rivaroxaban regimen. History of venous thromboembolism was the only significant demographic risk factor for post-operative venous thromboembolism (0.87% vs. 3.54%, p  = 0.0002). Conclusion In daily clinical practice, extended aspirin regimen is at least as effective as modified rivaroxaban for preventing clinically important venous thromboembolism among patients undergoing hip or knee arthroplasty who are discharged from the hospital without complications. Aspirin can be considered a safe and effective agent in the prevention of venous thromboembolism after total hip or total knee replacement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Delayed-Action Preparations; Elective Surgical Procedures; Enoxaparin; Female; Humans; Ireland; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Rivaroxaban; Socioeconomic Factors; Venous Thromboembolism; Young Adult

Topics: Administration, Oral; Anticoagulants; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

Hospitalized patients with acute medical illnesses are at risk for venous thromboembolism (VTE) during and after a hospital stay. Risk factors include physical immobilization and underlying pathophysiologic processes that activate the coagulation pathway and are still present after discharge. Strategies for optimal pharmacologic VTE thromboprophylaxis are evolving, and recommendations for VTE prophylaxis can be further refined to protect high-risk patients after hospital discharge. An early study of extended VTE prophylaxis with a parenteral agent in medically ill patients yielded inconclusive results with regard to efficacy and bleeding. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, extended use of betrixaban halved symptomatic VTE, decreased hospital readmission, and reduced stroke and major adverse cardiovascular events compared with standard enoxaparin prophylaxis. Based on findings from APEX, the Food and Drug Administration approved betrixaban in 2017 for extended VTE prophylaxis in acute medically ill patients. In the Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER) study, extended use of rivaroxaban halved symptomatic VTE in high-risk medical patients compared with placebo. In 2019, rivaroxaban was approved for extended thromboprophylaxis in high-risk medical patients, thus making available a new strategy for in-hospital and post-discharge VTE prevention. To address the critical unmet need for VTE prophylaxis in medically ill patients at the time of hospital discharge, the North American Thrombosis Forum (NATF) is launching the Anticoagulation Action Initiative, a comprehensive consensus document that provides practical guidance and straightforward, patient-centered recommendations for VTE prevention during hospitalization and after discharge.

Topics: Adult; Aged; Anticoagulants; Benzamides; Hospitalization; Humans; Medication Adherence; Middle Aged; Patient Discharge; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Venous Thromboembolism

Topics: 4-Hydroxycoumarins; Adult; Aftercare; Anticoagulants; Antiphospholipid Syndrome; England; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Heparin, Low-Molecular-Weight; Humans; Incidence; Indenes; International Normalized Ratio; Neoplasms; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; State Medicine; Systematic Reviews as Topic; Thrombophilia; Vena Cava Filters; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; Humans; Neoplasms; Pandemics; Pneumonia, Viral; Rivaroxaban; SARS-CoV-2; Thrombosis; Venous Thromboembolism

Topics: Drug Monitoring; Factor Xa Inhibitors; Female; Humans; Milk, Human; Postpartum Period; Pyrazoles; Pyridones; Rivaroxaban; Time Factors; Venous Thromboembolism

Warfarin is an anticoagulant medication proven effective in the initial treatment and secondary prevention of venous thromboembolism. Anti-Xa direct oral anticoagulants are alternatives to warfarin; however there is limited data assessing satisfaction after switching from warfarin to an anti-Xa direct oral anticoagulant in patients for treatment of venous thromboembolism.. To assess medication satisfaction in patients requiring anticoagulation for venous thromboembolism after conversion from warfarin to an anti-Xa direct oral anticoagulant.. A retrospective cohort study with prospective assessment of satisfaction and review of adverse events following anti-Xa direct oral anticoagulant replacement of warfarin for treatment of venous thromboembolism. Out of 165 patients who had switched from warfarin to rivaroxaban or apixaban from an outpatient haematology practice, 126 patients consented for a survey of patient's relative satisfaction of anti-Xa direct oral anticoagulant therapy compared with previous warfarin therapy using the Anti-Clot Burden and Benefits Treatment Scale and SWAN Score.. The mean Anti-Clot Burden and Benefits and SWAN Score was 93% (56/60) and 83% (24.8/30) respectively reflecting high satisfaction with anti-Xa direct oral anticoagulants. 120 patients stated preference for anti-Xa direct oral anticoagulants over warfarin. Leading perceptions driving this was the reduction in frequency of medical contact and fewer bleeding side effects. Thirteen patients (10.3%) experienced an adverse event after the anti-Xa direct oral anticoagulant switch (majority were non-major bleeding) but most remained on anti-Xa direct oral anticoagulant treatment after management options were implemented with continued high satisfaction scores.. Patient satisfaction with anti-Xa direct oral anticoagulant therapy for the treatment and prevention of venous thromboembolism after switching from warfarin in routine clinical practice appeared high. Improved patient convenience including reduced frequency of medical contact and fewer unpredictable side effects were perceived as significant advantages of anti-Xa direct oral anticoagulants compared to warfarin.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Patient Satisfaction; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Surveys and Questionnaires; Time Factors; Venous Thromboembolism; Warfarin; Young Adult

To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg.. Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview.. Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01).. Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

Topics: Acute Disease; Anticoagulants; Body Weight; Disease Management; Drug Therapy, Combination; Factor Xa Inhibitors; Health Care Surveys; Hemorrhage; Humans; Pyrazoles; Pyridones; Registries; Rivaroxaban; Venous Thromboembolism

Andexanet alfa, a novel anticoagulation reversal agent for factor Xa inhibitors, was recently approved. Traumatic intracranial hemorrhage presents a prime target for this drug. The Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors study established the efficacy of andexanet alfa in reversing factor Xa inhibitors. However, the association between anticoagulation reversal and traumatic intracranial hemorrhage progression is not well understood. The objective of this study was to determine progression rates of patients with traumatic intracranial hemorrhage on factor Xa inhibitors prior to hospitalization who were managed without the use of andexanet alfa.. A retrospective cohort study was performed between 2016 and 2019 at a single institution. An institutional traumatic brain injury (TBI) registry was queried. Patients with recorded use of apixaban or rivaroxaban <18 hours before injury were included. The primary study outcome was <35% increase in hemorrhage volume or thickness on repeated head computed tomography (CT) scans.. We identified 25 patients meeting the inclusion criteria. Two patients were excluded because of a lack of necessary CT data. Twelve patients (52%) were receiving apixaban, and 11 were (48%) on rivaroxaban. On admission CT scan, 14 patients had subdural hematoma, 6 had traumatic intraparenchymal hemorrhage, and 3 had subarachnoid hemorrhage. Anticoagulation reversal was attempted in 17 patients (74%), primarily using 4-factor prothrombin complex concentrate. Twenty patients (87%) were adjudicated as having excellent or good hemostasis on repeat imaging.. Our results indicate that patients on factor Xa inhibitors with complicated mild TBI have a similar intracranial hemorrhage progression rate to patients who are not anticoagulated or anticoagulated with a reversible agent. The hemostatic outcomes in our cohort were similar to those reported after andexanet alfa administration.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Blood Coagulation Factors; Cerebral Hemorrhage, Traumatic; Cohort Studies; Disease Progression; Factor Xa; Factor Xa Inhibitors; Female; Glasgow Coma Scale; Hematoma, Subdural, Intracranial; Hemostasis; Humans; Intracranial Hemorrhage, Traumatic; Male; Middle Aged; Plasma; Platelet Transfusion; Pyrazoles; Pyridones; Recombinant Proteins; Retrospective Studies; Risk; Risk Factors; Rivaroxaban; Subarachnoid Hemorrhage, Traumatic; Tomography, X-Ray Computed; Venous Thromboembolism

Topics: Aftercare; Anticoagulants; Hospitals; Humans; Patient Discharge; Rivaroxaban; Venous Thromboembolism

We studied the safety and efficacy of multimodal thromboprophylaxis in patients with a history of venous thromboembolism (VTE) who undergo total hip arthroplasty (THA) within the first 120 postoperative days, and the mortality during the first year. Multimodal prophylaxis includes discontinuation of procoagulant medications, VTE risk stratification, regional anaesthesia, an intravenous bolus of unfractionated heparin prior to femoral preparation, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient's risk of VTE.. Between 2004 to 2018, 257 patients with a proven history of VTE underwent 277 primary elective THA procedures by two surgeons at a single institution. The patients had a history of deep vein thrombosis (DVT) (186, 67%), pulmonary embolism (PE) (43, 15.5%), or both (48, 17.5%). Chemoprophylaxis included aspirin (38 patients), anticoagulation (215 patients), or a combination of aspirin and anticoagulation (24 patients). A total of 50 patients (18%) had a vena cava filter in situ at the time of surgery. Patients were followed for 120 days to record complications, and for one year to record mortality.. Postoperative VTE was diagnosed in seven patients (2.5%): DVT in five, and PE with and without DVT in one patient each. After hospitalization, three patients required readmiss-ion for evacuation of a haematoma, one for wound drainage, and one for monitoring of an elevated international normalized ratio (INR). Seven patients died (2.5%). One patient died five months postoperatively of a PE during open thrombectomy. She had discontinued anticoagulation. One patient died of a haemorrhagic stroke while receiving Coumadin. PE or bleeding was not suspected in the remaining five fatalities.. Multimodal prophylaxis is safe and effective in patients with a history of VTE. Postoperative anticoagulation should be prudent as very few patients developed VTE (2.5%) or died of suspected or confirmed PE. Mortality during the first year was mostly unrelated to either VTE or bleeding. Cite this article:

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Conduction; Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Chemoprevention; Early Ambulation; Elective Surgical Procedures; Female; Follow-Up Studies; Heparin; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Retrospective Studies; Risk Factors; Rivaroxaban; Venous Thromboembolism; Warfarin

The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance [CrCl] levels ≤50 mL/min and/or body weight ≤50kg) with venous thromboembolism (VTE) have not been consistently compared.. We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban for initial and long-term therapy.. From January 2013 to October 2019, 36,889 patients were recruited, of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting within the first 48 h: rivaroxaban 711 and apixaban 288. Median duration of therapy was: 113 vs. 111 days. A substantial amount of patients in both subgroups (25% vs. 40%) received non-recommended doses of DOACs. During anticoagulation, 13 patients developed VTE recurrences, 18 had major bleeding and 36 died. When only considering patients receiving recommended doses (n = 705), there were no differences between drugs in the rate of the composite outcome (rate ratio [RR]: 1.08; 95%CI: 0.35-3.30) or all-cause death (RR: 0.99; 95%CI: 0.32-3.08). On multivariable analysis, patients receiving rivaroxaban or apixaban at recommended doses had a similar risk for the composite outcome (hazard ratio: 1.34; 95%CI: 0.35-5.06).. The use of rivaroxaban or apixaban at recommended doses in fragile patients with VTE was associated with a similar risk for VTE recurrences or major bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Humans; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Two dogs with immune-mediated hemolytic anemia complicated with thromboembolism were presented. Both of the dogs were initially treated with immunosuppressive therapy in conjunction with dalteparin and clopidogrel. Although the immunosuppressive therapy was effective, peritoneal effusion due to thromboembolism was observed during the course of the disease in these dogs. After initiation of rivaroxaban treatment, peritoneal effusion decreased immediately in parallel with the normalization of D-dimer, antithrombin (AT), and thrombin-antithrombin complex (TAT). Hematochezia, cutaneous hemorrhage, and hematuria were observed as adverse events after administration of rivaroxaban in one case. Rivaroxaban was effective for the control of thromboembolism secondary to immune-mediated hemolytic anemia, and D-dimer, AT, and TAT were useful to monitor the status of thromboembolic disease in dogs.

Topics: Animals; Anticoagulants; Dog Diseases; Dogs; Gastrointestinal Hemorrhage; Rivaroxaban; Venous Thromboembolism

Direct oral anticoagulants (DOACs) have promised superior efficacy to low molecular weight heparins in the prevention of venous thromboembolism (VTE) in total hip and knee arthroplasty. However, there are concerns about raised associated bleeding and wound problems with these agents. This study aims to evaluate and compare the efficacy and safety of the 3 DOAC drugs: rivaroxaban, dabigatran and apixaban.. The primary outcome measures were rate of symptomatic VTE and major bleeding. Secondary outcome measures were wound healing problems and requirement for return to theater. A total of 2431 patients received one of the DOAC drugs as thromboprophylaxis following total hip arthroplasty (35 days) or total knee arthroplasty (14 days) between 2011 and 2015. Binary variables were compared between the 3 groups by using the chi-squared test or Fisher's exact test. Relative risks of selected primary and secondary end points were also calculated for the prespecified pairwise comparison.. The overall symptomatic VTE rate was 2%. Rivaroxaban had a statistically significant superior efficacy for overall VTE prevention (0.8% vs 2.6%) compared with dabigatran (P < .01) and apixaban (P < .01), and deep vein thrombosis prevention (0.3% vs 2.2%) over dabigatran (P < .01). The overall rate of major bleeding was 1.2% with no significant difference observed between the 3 studied drugs.. All 3 drugs had symptomatic VTE rates comparable with low molecular weight heparin from the published literature. Rivaroxaban appears to have superior efficacy in VTE prevention over apixaban and dabigatran. No statistical difference was observed for major bleeding with any of the 3 agents.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dabigatran; Humans; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Little is known about the impact of oral anticoagulation (OAC) choice on healthcare encounters during venous thromboembolism (VTE) primary treatment. Among anticoagulant-naïve patients with VTE, we tested the hypotheses that healthcare utilization would be lower among users of direct OACs (DOACs; rivaroxaban or apixaban) than among users of warfarin. MarketScan databases for years 2016 and 2017 were used; healthcare utilization was identified in the first 6 months after initial VTE diagnoses. The 23,864 patients with VTE had on average 0.2 ± 0.5 hospitalizations, spent 1.3 ± 5.2 days in the hospital, had 5.7 ± 5.1 outpatient encounters, and visited an emergency department 0.4 ± 1.1 times. As compared to warfarin, rivaroxaban and apixaban were associated with fewer hospitalizations, days hospitalized, outpatient office visits, and emergency department visits after accounting for age, sex, comorbidities, and medications. Hospitalization rates were 24% lower (incidence rate ratio (IRR): 0.76; 95% CI: 0.69, 0.83) with rivaroxaban and 22% lower (IRR: 0.78; 95% CI: 0.71, 0.87) with apixaban, as compared to warfarin (IRR: 1.00 (reference)). Healthcare utilization was similar between apixaban and rivaroxaban users. Patients with VTE prescribed rivaroxaban and apixaban had lower healthcare utilization than those prescribed warfarin, while there was no difference when comparing apixaban to rivaroxaban. These findings complement existing literature supporting the use of DOACs over warfarin.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Anticoagulants; Databases, Factual; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Health Resources; Hospitalization; Humans; Male; Middle Aged; Office Visits; Pyrazoles; Pyridones; Rivaroxaban; Time Factors; Treatment Outcome; United States; Venous Thromboembolism; Warfarin

Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer. VTE complications may have a substantial impact on prognosis, quality of life and care in patients with cancer. Patients with cancer-related VTE are at increased risk of developing recurrent VTE compared to patients without cancer, but also have a higher risk of major bleeding. In the last years, direct oral anticoagulants (DOACs) have been evaluated in a head-to-head comparison with low molecular weight heparin (LMWH) in two randomized trials for the long-term treatment of VTE in patients with advanced cancer. The results of these trials show that DOACs have a similar efficacy profile, but probably higher risk of bleeding, compared to LMWH dalteparin. Because DOACs offer a simple oral treatment regimen without the need for anticoagulation monitoring, they could be attractive alternatives to LMWHs in these setting. The American Society of Clinical Oncology guidelines, published in August 2019, recommend LMWH, edoxaban and rivaroxaban as first-choice therapies for long-term anticoagulation in cancer patients with VTE. However, several practical issues should be considered concerning the long-term use of DOAC treatment in patients with cancer. Major concerns have been highlighted about the gastrointestinal bleeding risk in patients with gastrointestinal cancers and the potential drug-drug interactions in combination for some specific anticancer therapies. Several studies comparing DOACs with LMWH are currently ongoing to refine our knowledge concerning treatment with DOACs in patients with cancer-associated VTE.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Quality of Life; Rivaroxaban; Venous Thromboembolism

Limited economic evaluation data for rivaroxaban compared with standard of care (SoC) exists in China. The objective of this analysis was to evaluate the cost-effectiveness of rivaroxaban compared with current SoC (enoxaparin overlapped with warfarin) for the treatment of acute deep vein thrombosis (DVT) in China.. A Markov model was adapted from a payer's perspective to evaluate the costs and quality-adjusted life years (QALYs) of patients with DVT treated with rivaroxaban or enoxaparin/warfarin. Clinical data from the EINSTEIN-DVT trial were obtained to estimate the transition probabilities. Data on Chinese health resource use, unit costs and utility parameters were collected from previously published literature and used to estimate the total costs and QALYs. The time horizon was set at 5 years and a 3-month cycle length was used in the model. A 5% discount rate was applied to the projected costs. One-way sensitivity analyses and probabilistic sensitivity analyses were undertaken to assess the impact of uncertainty on results.. Rivaroxaban therapy resulted in an increase of 0.008 QALYs and was associated with lower total costs compared with enoxaparin/warfarin (US$4744.4 vs US$5572.4, respectively), demonstrating it to be a cost-saving treatment strategy. The results were mainly sensitive to length of hospitalisation due to DVT on enoxaparin/warfarin, cost per day of hospitalisation and the difference in length of stay of rivaroxaban-treated and enoxaparin/warfarin-treated patients.. Rivaroxaban therapy resulted in a cost saving compared with enoxaparin/warfarin for the anticoagulation treatment of patients with hospitalised acute DVT in China.. NCT00440193; Post-results.

Topics: Anticoagulants; China; Cost-Benefit Analysis; Enoxaparin; Humans; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Rivaroxaban; Thrombophilia; Venous Thromboembolism

: Hereditary protein S deficiency is an autosomal dominant disorder associated with a high risk of venous thromboembolism (VTE) and usually results from mutations of PROS1. Historically heparin and warfarin have been applied as recommended treatment of VTE. Recent researches showed that rivaroxaban provided more consistent and predictable anticoagulation than warfarin. However, it is unknown whether rivaroxaban is effective for the treatment of VTE in patients with thrombophilia, including protein S deficiency, due to lack of evidence. Here, we report two cases of recurrent VTE in two patients with hereditary protein S deficiency, owing to the same nonsense mutation in PROS1, which were successfully treated by rivaroxaban monotherapy.

Topics: Adult; Factor Xa Inhibitors; Humans; Male; Protein S; Protein S Deficiency; Rivaroxaban; Venous Thromboembolism

Guidelines provide differing recommendations regarding direct-acting oral anticoagulants vs low-molecular-weight heparin (LMWH) for treatment of cancer-associated thrombosis (CAT). This study was undertaken to evaluate the effectiveness and safety of rivaroxaban vs LMWH for treatment of CAT. Using US Surveillance, Epidemiology and End Results-Medicare-linked data from 2013 through 2016, we evaluated adults with active breast, lung, ovarian, or pancreatic cancer, who were admitted to the hospital or treated in the emergency department for CAT and were prescribed rivaroxaban or LMWH for outpatient anticoagulation. Patients with luminal gastrointestinal or genitourinary cancers were excluded. Rivaroxaban and LMWH users were 1:1 propensity score matched. Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately, and mortality at 6 months, using an intent-to-treat approach. On-treatment analysis after 12 months was also performed. Proportional hazards models for the subdistribution of competing risk were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 529 rivaroxaban- and 529 LMWH-treated patients with CAT. Rivaroxaban was not associated with differences in risk of the composite outcome (HR, 0.71; 95% CI, 0.41-1.22), major bleeding (HR, 1.01; 95% CI, 0.50-2.01), or mortality (HR, 0.87; 95% CI, 0.70-1.07) vs LMWH, but it reduced recurrent thrombosis (HR, 0.37; 95% CI, 0.15-0.95). On-treatment analysis at 12 months showed similar results. Rivaroxaban may be a reasonable alternative to LMWH for patients with CAT without gastrointestinal or genitourinary cancer.

Topics: Adult; Aged; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Medicare; Neoplasms; Rivaroxaban; United States; Venous Thromboembolism

Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses for, at least, the most severely ill patients; this practice is not free of risks, which is why only thromboembolic prophylaxis is recommended by other consensuses. In the case of previously anticoagulated patients, changing the oral anticoagulant for a low molecular weight heparin (LMWH) is generally recommended. We present the cases of two patients admitted due to COVID-19, without serious clinical data, in whom anticoagulation (acenocoumarol and rivaroxaban, respectively) was replaced by LMWH at therapeutic doses, both presenting abdominal bleeding. This type of bleeding is an infrequent complication in anticoagulated patients, but the concurrence of two cases in a short period of time in the context of the COVID-19 pandemic leads us to consider that there is not yet any clear evidence on therapeutic anticoagulation in SARS-CoV-2 infection.

Topics: Abdomen; Acenocoumarol; Aged, 80 and over; Anticoagulants; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Hematoma; Heparin, Low-Molecular-Weight; Humans; Pandemics; Pneumonia, Viral; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism

There is insufficient real-world data on the current status of Japanese patients with venous thromboembolism (VTE) or its treatment and prevention with rivaroxaban.Methods and Results:In this multicenter, prospective, observational study conducted in Japan, 1,039 patients with acute symptomatic/asymptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) with or without DVT prescribed rivaroxaban were enrolled at 152 institutions and observed for a median of 21.3 months. Mean age was 68.0±14.7 years, mean body weight was 60.3±14.1 kg, 59.0% were females, and 19.0% had active cancer. Incidences of recurrence or aggravation of symptomatic VTE (primary effectiveness outcome) and major bleeding (principal safety outcome) were 2.6% and 2.9% per patient-year, respectively. These outcomes did not differ between patients with DVT and those with PE (primary effectiveness outcome: 2.6% vs. 2.5% per patient-year, P=0.810; principal safety outcome: 3.5% vs. 2.4% per patient-year, P=0.394). The incidence of composite clinically relevant events, including recurrence or aggravation of symptomatic VTE, acute coronary syndrome, ischemic stroke, all-cause death, or major bleeding events, was 9.2% per patient-year. Multivariate analysis revealed that male sex, being underweight, having active cancer, chronic heart and lung disease, and previous stroke were independent determinants for composite clinically relevant events.. In Japanese clinical practice, a single-drug approach with rivaroxaban was demonstrated to be a valuable treatment for a broad range of VTE patients.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Neoplasms; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Direct oral anticoagulants, such as apixaban and rivaroxaban, are important for the treatment and prophylaxis of venous thromboembolism and to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Because apixaban and rivaroxaban are predominantly eliminated by cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp), concomitant use of combined P-gp and strong CYP3A4 inhibitors and inducers should be avoided. Physiologically-based pharmacokinetic models for apixaban and rivaroxaban were developed to estimate the net effect of CYP3A induction, P-gp inhibition, and P-gp induction by rifampicin. The disposition of rivaroxaban is more complex compared with apixaban because both hepatic and renal P-gp is considered to contribute to rivaroxaban elimination. Furthermore, organic anion transporter-3, a renal uptake transporter, may also contribute the elimination of rivaroxaban from systemic circulation. The models were verified with observed clinical drug-drug interactions with CYP3A and P-gp inhibitors. With the developed models, the predicted area under the concentration time curve and maximum concentration ratios were 0.43 and 0.48, respectively, for apixaban, and 0.50-0.52 and 0.72-0.73, respectively, for rivaroxaban when coadministered with 600 mg multiple doses of rifampicin and that were very close to observed data. The impact of each of the elimination pathways was assessed for rivaroxaban, and inhibition of CYP3A led to a larger impact over intestinal and hepatic P-gp. Inhibition of renal organic anion transporter-3 or P-gp led to an overall modest interaction. The developed apixaban and rivaroxaban models can be further applied to the investigation of interactions with other P-gp and/or CYP3A4 inhibitors and inducers.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Biological Transport; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Embolism; Factor Xa Inhibitors; Humans; Pyrazoles; Pyridones; Rifampin; Rivaroxaban; Stroke; Venous Thromboembolism

To evaluate the short-term (12 weeks) safety and utilisation of rivaroxaban prescribed to new-user adult patients for the treatment of deep vein thrombosis and pulmonary embolism and for the prevention of recurrent deep vein thrombosis and pulmonary embolism in a secondary care setting in England and Wales.. An observational cohort study using the technique of Specialist Cohort Event Monitoring.. The Rivaroxaban Observational Safety Evaluation study was conducted across 87 participating National Health Service secondary care trusts in England and Wales.. 1532 patients treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism from September 2013 to January 2016.. Non-interventional postauthorisation safety study of rivaroxaban. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Risk of major bleeding in gastrointestinal, intracranial, and urogenital sites and (2) risk of all major and clinically relevant non-major bleeds.. Of a total of 4846 patients enrolled in the study from September 2013 to January 2016, 1532 were treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism. The median age of the deep vein thrombosis/pulmonary embolism cohort was 63 years, and 54.6% were men. The risk of major bleeding within the gastrointestinal, urogenital and intracranial primary sites was 0.7% (n=11), 0.3% (n=5) and 0.1% (n=1), respectively. The risk of major bleeding in all sites was 1.5% (n=23) at a rate of 8.3 events per 100 patient-years.. In terms of the primary outcome risk of major bleeding in gastrointestinal, intracranial and urogenital sites, the risk estimates in the population using rivaroxaban for deep vein thrombosis/pulmonary embolism were low (<1%) and consistent with the risk estimated from clinical trial data and in routine clinical practice.. ClinicalTrials.gov Registry (NCT01871194); ENCePP Registry (EUPAS3979).

Topics: Aged; Anticoagulants; Cohort Studies; England; Female; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Rivaroxaban; Secondary Care; State Medicine; United Kingdom; Venous Thromboembolism; Venous Thrombosis; Wales

The purpose of this meta-analysis is to compare the efficacy and safety of aspirin and rivaroxaban in the prevention of venous thromboembolism (VTE) following either total knee arthroplasty or total hip arthroplasty.. A comprehensive literature search of several electronic databases (PubMed, Embase, and Web of Science) was conducted to identify relevant studies. Outcomes of interest included VTE rate, deep vein thrombosis (DVT) rate, pulmonary embolism rate, major bleeding events, mortality rate, blood transfusion, and wound complication. Risk ratio (RR) with 95% confidence intervals (95%CIs) were calculated using a fixed-effects model or random-effects model.. A total of 8 studies with 97,677 patients met the inclusion criteria and were included in this meta-analysis. Compared with rivaroxaban, aspirin had a significantly higher incidence of DVT (RR = 1.48, 95%CI: 1.27, 1.72; P < .001), and decreased risk of blood transfusion (RR = 0.94, 95%CI: 0.93, 0.94; P < .001). However, there were no significant differences between the 2 drugs in terms of total VTE rate (RR = 1.39%, 95%CI: 0.94, 2.05; P = .101), pulmonary embolism rate (RR = 1.64, 95%CI: 0.92, 2.92; P = .094), mortality rate (RR = 1.13, 95%CI: 0.15, 8.27; P = .907), major bleeding (RR = 1.00, 95%CI: 0.44, 2.27; P = .995), and wound complication rate (RR = 0.37, 95%CI: 0.07, 1.87; P = .229).. Our results suggested that aspirin and rivaroxaban offered similar effect in the prevention of VTE after total knee arthroplasty or total hip arthroplasty. However, rivaroxaban seemed to have better effect than aspirin in reducing the risk of DVT, and aspirin was safer than rivaroxaban in decreasing the blood transfusion rate.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Blood Transfusion; Hemorrhage; Humans; Meta-Analysis as Topic; Pulmonary Embolism; Research Design; Rivaroxaban; Surgical Wound Infection; Systematic Review as Topic; Venous Thromboembolism; Venous Thrombosis

<b>Purpose: </b>Venous thromboembolism (VTE) after colorectal surgery is a well-documented complication, resulting in a general recommendation of extended post-discharge prophylaxis. Rivaroxaban, a factor Xa inhibitor, is a daily tablet approved for treatment of VTE and prophylaxis after orthopedic surgery. <br><b>Aim: </b>The purpose of this study is to evaluate the safety of rivaroxaban for extended prophylaxis after major abdominal and pelvic surgery. <br><b>Methods: </b>This is a retrospective review of patients undergoing major colorectal surgery at a regional hospital in Kiev, Ukraine. Patients received peri-operative VTE prophylaxis with subcutaneous heparin and then transitioned to rivaroxaban for a total of 30 days. Occurrences of major or minor bleeding, blood transfusion, and a need for re-intervention were noted. Phone surveys were administered on post-operative day 30 to assess compliance and satisfaction with the regimen. <br><b>Results: </b>A total of 51 patients were included in the study with an average age of 62.4 years. Seventy-one percent of the cases were abdominal, 29% were pelvic cases and 59% were done laparoscopically. There was one episode of major intra-abdominal bleeding requiring return to the operating room. There were 2 minor bleeding episodes which did not require intervention. There were no VTE events in the group. The phone survey response rate was 100%. All but one patient reported having completed the full course of rivaroxaban. Patients reported that oral prophylaxis was easy to adhere to and preferable compared to injections. <br><b>Conclusion: </b>Implementation of extended prophylaxis with rivaroxaban is easy, safe and does not increase rates of postoperative bleeding.

Topics: Aftercare; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

A morbidly obese patient with history of deep vein thrombosis and pulmonary embolism was diagnosed with an acute left upper extremity deep vein thrombosis and started on rivaroxaban. Three months later, the patient returned with swelling in the right arm and was found to have a right brachial thrombosis. Anticoagulant therapy was switched to a low-molecular-weight heparin, and patient was discharged on enoxaparin along with an order to follow-up with a hematologist. Subanalyses from randomized controlled trials, pharmacokinetic/pharmacodynamic, and real-world studies suggest that rivaroxaban may be effective and safe in morbidly obese patients for primary and secondary prevention of venous thromboembolism. However, the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis does not recommend the use of direct-acting oral anticoagulants in this population. If used, drug levels should be monitored to guide the therapy. Due to the disparity in data to show efficacy and safety of rivaroxaban in morbidly obese subjects, the interpatient variability of rivaroxaban's effects in subjects, and the lack of defined therapeutic range for rivaroxaban drug concentration, rivaroxaban should be used cautiously in this population.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Obesity, Morbid; Pulmonary Embolism; Rivaroxaban; Upper Extremity Deep Vein Thrombosis; Venous Thromboembolism

Topics: Aftercare; Anticoagulants; Benzamides; Duration of Therapy; Enoxaparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Length of Stay; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Child; Heparin; Humans; Rivaroxaban; Thrombolytic Therapy; Venous Thromboembolism

Topics: Anticoagulants; Cost-Benefit Analysis; Female; Health Expenditures; Health Resources; Humans; Male; Markov Chains; Middle Aged; Models, Econometric; Network Meta-Analysis; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Rivaroxaban; United Kingdom; Venous Thromboembolism

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT.. To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK.. Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin.. Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Epistaxis; Female; Humans; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Telangiectasia, Hereditary Hemorrhagic; Venous Thromboembolism; Warfarin

Limited data exist on direct-acting oral anticoagulants in morbidly obese patients with venous thromboembolism (VTE). We compared clinical and health/economic outcomes with rivaroxaban versus warfarin for VTE treatment in morbidly obese patients.. This retrospective 1:1 propensity score matched cohort study analyzed data from 2 US claims databases. VTE patients initiating rivaroxaban or warfarin were identified who had diagnosis codes for morbid obesity (ICD-9:278.01,V85.4; ICD-10:E66.01,E66.2,Z68.4) 12 months pre- or 3 months post-initiation and followed ≥3 months. Intent-to-treat (ITT) and on-treatment (OT) analyses were conducted using conditional logistic regression and generalized linear models to compare recurrent VTE and major bleeding risks, healthcare resource utilization (HRU), and per patient per year (PPPY) costs.. In total, 2890 matched pairs of morbidly obese VTE patients initiating rivaroxaban or warfarin were identified. Risks of recurrent VTE (ITT: OR: 0.99; 95% CI: 0.85-1.14) and major bleeding (OT: OR: 0.75; 95% CI: 0.47-1.19) were similar for cohorts. Anti-Factor Xa laboratory measurement was performed on <1% of rivaroxaban cohort. Hospitalizations (OR: 0.86; 95% CI: 0.77-0.96) and outpatient visits (OR: 0.23; 95% CI: 0.10-0.56), were lower with rivaroxaban versus warfarin (ITT analysis). Average total medical costs PPPY were $2829 lower with rivaroxaban versus warfarin ($34,824 vs $37,653), mainly driven by hospitalization costs. Total healthcare costs (including pharmacy) were similar ($43,034 vs $44,565).. Morbidly obese VTE patients receiving rivaroxaban had similar risks of recurrent VTE and major bleeding versus warfarin. Rivaroxaban treatment yielded significantly less HRU and total medical costs, with similar total healthcare costs between groups.

Topics: Adult; Aged; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Obesity, Morbid; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

Although several studies now support the use of aspirin for venous thromboembolism (VTE) prophylaxis in primary total hip arthroplasty (THA) and total knee arthroplasty (TKA), the optimal chemoprophylactic agent in revision THA and TKA is not clear. The purpose of this study was to determine if the type of chemoprophylaxis has an effect on the VTE rate in patients undergoing revision total joint arthroplasty (TJA). The second aim was to compare differences in rates of wound drainage in primary and revision TJA stratified by the postoperative chemoprophylaxis used. The authors retrospectively reviewed 1917 consecutive patients undergoing primary and revision TJA. Individual records were reviewed for patient demographics, medical comorbidities, type of chemoprophylaxis, VTE risk factors, intraoperative data, and postoperative complications. Outcomes, including VTE rate and wound complications, were compared between types of anticoagulant therapy used postoperatively. Of the 1917 patients, there were 742 (38.7%) primary TKAs, 326 (17%) revision TKAs, 608 (31.7%) primary THAs, and 241 (12.6%) revision THAs. The most common prophylactic agent used was rivaroxaban (40.6%), followed by warfarin (28.5%) and aspirin (27.6%). Type of chemoprophylaxis was not associated with postoperative VTE or wound drainage (P>.05). Although revision surgery was an independent risk factor for wound drainage (odds ratio, 3.201; 95% confidence interval, 1.594-6.426; P=.001), it was not a risk factor for VTE (odds ratio, 1.847; 95% confidence interval, 0.423-8.053; P=.414). Revision arthroplasty alone was not associated with an increased rate of VTE. Aspirin is as effective as other chemoprophylactic agents without the increased risk of bleeding in low-risk patients. [Orthopedics. 2019; 42(6):323-329.].

Topics: Adult; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Female; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Reoperation; Retrospective Studies; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

To compare the efficacy and safety of aspirin with rivaroxaban following treatment with enoxaparin for prevention of venous thromboembolism (VTE) after hip fracture surgery (HFS).. A total of 390 patients were enrolled in the trial. According to an odd or even number at the end of their registration number, the patients were divided into the aspirin group (n = 198) and the rivaroxaban group (n = 192). All patients were given enoxaparin subcutaneous injection after the operation and returned to the routine dose the next day until postoperative day five. The patients in the aspirin group received an additional 16 days of thromboprophylaxis with 100 mg of aspirin once daily. The rivaroxaban group was assigned to receive an additional 16 days of thromboprophylaxis with 10 mg of oral rivaroxaban once daily. Patients were followed for 90 days regarding VTE and bleeding complications.. The incidence of VTE in the aspirin group and rivaroxaban group was 6.6% (13/198) and 5.7% (11/192), respectively (P = 0.83). The rate of major bleeding events occurred in two (1.0%) patients in the aspirin group and in one patient (0.5%) in the rivaroxaban group (P = 1.0). A combination of major bleeding and clinically relevant nonmajor bleeding occurred in five patients (2.5%) in the aspirin group and in six patients (3.1%) in the rivaroxaban group (P = 0.77). During the 90-day follow-up, a pulmonary embolism developed in one patient (0.5%) in the aspirin group and none in the rivaroxaban group (P = 1.0).. Extended prophylaxis for 21 days with aspirin was equivalent to the direct oral anticoagulant rivaroxaban after hip fracture surgery with an initial 5-day postoperative course of enoxaparin. Aspirin may be an effective, safe, convenient, and cheap alternative for extended prophylaxis after hip fracture surgery.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Drug Therapy, Combination; Enoxaparin; Female; Hip Fractures; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

This is a case report of a 48-year-old woman who presented with heavy per vaginal bleeding to the emergency department after being commenced on direct oral anticoagulants (DOACs) for venous thromboembolism. She had significant bleeding which initially required resuscitation and stabilisation. Her symptoms were ultimately managed by changing her anticoagulation agent to therapeutic low molecular weight heparin with Clexane

Topics: Administration, Oral; Anticoagulants; Contraceptives, Oral; Diagnosis, Differential; Enoxaparin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Rivaroxaban; Treatment Outcome; Uterine Hemorrhage; Venous Thromboembolism

BACKGROUND Several studies have described an increased incidence of venous thromboembolism in inflammatory conditions such as sarcoidosis. CASE REPORT We report a case of a 27-year-old African-American man who developed sarcoidosis with pulmonary involvement after 4 years of unexplained thromboembolism. CONCLUSIONS This report discusses the relationship between sarcoidosis and venous thromboembolism. Our case raises questions about this relationship. Can sarcoidosis lead to an inflammatory and prothrombotic state prior to the development of other manifestations?

Topics: Adult; Anti-Inflammatory Agents; Cough; Diagnosis, Differential; Dyspnea; Factor Xa Inhibitors; Humans; Male; Prednisone; Rivaroxaban; Sarcoidosis; Tomography Scanners, X-Ray Computed; Venous Thromboembolism

All cancers increase developing venous thromboembolism risk, and VTE is the second-leading cause of death among cancer patients. The anticoagulant drugs are considered to be the optimal treatment for patients with cancer-associated VTE. However, there is still controversy whether rivaroxaban, a new oral anticoagulant, can lead to better outcomes globally.. We will search PubMed, Web of Science, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure for relevant published studies before 1 September, 2019, without any language restrictions. Only published randomized controlled trials that meet the inclusion criteria will be included. Subgroup analysis of the type of cancer, the type of VTE, cancer stage, age, sex, ethnicity, history of smoking and drinking as well as the mean, dose and duration of anticoagulants will be performed.. Our study aims to estimate the efficacy and safety of rivaroxaban for patients with cancer-associated VTE and to provide recommendations to key stakeholders.. PROSPERO, October 23, 2019, CRD42019143265, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=143265.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Humans; Male; Meta-Analysis as Topic; Neoplasms; Research Design; Rivaroxaban; Systematic Reviews as Topic; Treatment Outcome; Venous Thromboembolism

The objective of this study was to identify the optimal duration of pharmacological thromboprophylaxis after outpatient endovenous laser ablation (EVLA).. In this multicentre retrospective study in a university hospital, regional hospital and private practices, we collected the demographic, procedural and outcome data of all consecutive patients with varicose veins class C2 to C6 undergoing outpatient EVLA of truncal and accessory veins between February 2009 and December 2015. The cumulative primary efficacy endpoint consisted of endovenous heat-induced thrombosis (EHIT) class 2–4, deep vein thrombosis (DVT) and pulmonary embolism (PE) diagnosed with duplex ultrasound or computed tomography angiography after 1 and 4 weeks of follow-up. Cumulative secondary endpoints were complete ablation of the treated veins and major bleeding, skin burns and infection.. A total of 864 patients were treated with EVLA as an outpatient procedure. Of those, 35 patients were omitted because of therapeutic anticoagulation or dual antiplatelet therapy. Another 36 cases were excluded as the patients received pharmacological thromboprophylaxis for 5 days. A total of 793 were included in the final analysis. Of those, 225 patients (28.4%) received fondaparinux 2.5 mg s.c. for 3 days, 166 patients (20.9%) received rivaroxaban 10 mg p.o. for 3 days and 402 patients (50.7%) received rivaroxaban 10 mg for 10 days. The incidence of EHIT class 2–4 was 0.8% (n = 6) in total, 1.3% (n = 6) in group 1 (treated for 3 days) and 0.3% (n = 1) in group 2 (treated for 10 days) (odds ratio [OR] 0.19, confidence interval [CI] 0.02–1.66, p = 0.133). The cumulative primary composite endpoint at 4-week follow-up was 1.1% (n = 9) and was 2.1% (n = 8) in group 1 and 0.3% (n = 1) in group 2 (OR 0.0.12, CI 0.01–0.96, p = 0.046). Propensity score-matched analysis revealed no significant difference in the composite primary endpoint (CI −0.074 to 0.26). Complete occlusion rate was 99.2% in group 1 and 98.8% in group 2 (OR 0.61, CI 0.15–2.59, p = 0.506). No PE or major bleeding events occurred in either group. Propensity score-matched analysis showed no significant difference in the secondary endpoints.. Using propensity score-matched analysis we showed that pharmacological thromboprophylaxis after EVLA seems to be equally effective with 3 days or 10 days of treatment with a similar success rate and safety profile. Undoubtedly, a large randomised control trial, ideally including a group without pharmacological thromboprophylaxis, is needed to draw more definitive conclusions on the optimal duration of pharmacological post-EVLA thromboprophylaxis.

Topics: Ambulatory Surgical Procedures; Dose-Response Relationship, Drug; Drug Administration Schedule; Endovascular Procedures; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Laser Therapy; Male; Middle Aged; Propensity Score; Retrospective Studies; Rivaroxaban; Saphenous Vein; Varicose Veins; Venous Thromboembolism

Patients with gynecologic malignancies are at an increased risk for venous thromboembolism. National guidelines recommend treatment of an acute venous thromboembolism with low molecular weight heparin for 5-10 days followed by long-term secondary prophylaxis with low molecular weight heparin for at least six months. Non-vitamin K oral anticoagulants are not currently recommended to be used in cancer patients for the management of venous thromboembolism because robust data on their efficacy and safety have yet to become available in cancer patients. The objectives of this study were to determine the proportion of gynecologic oncology patients with venous thromboembolism using rivaroxaban compared to warfarin or low molecular weight heparin as well as compare the safety and efficacy of these anticoagulants.. This study was a retrospective pilot analysis of adult patients with gynecologic malignancies who received either rivaroxaban, warfarin or low molecular weight heparin for treatment of venous thromboembolism at Augusta University Medical Center from 1 July 2013 to 30 June 2015. Statistical comparisons between the enoxaparin and rivaroxaban group were made using T-tests and Chi-square or Fisher's exact tests, where appropriate.. Out of the 49 patients, 37% (18) patients were on rivaroxaban, 53% (26) on enoxaparin, and 10% (5) on warfarin. Only one patient (4%) in the enoxaparin group experienced a recurrent deep vein thrombosis while there were no cases of recurrent venous thromboembolism in the rivaroxaban and warfarin group. The incidence of major bleeding was 17% (. A high proportion of our gynecologic oncology patients received rivaroxaban for the management of venous thromboembolism. The sample size of this pilot analysis was too small to draw any conclusions regarding efficacy and safety of rivaroxaban compared with enoxaparin and warfarin. High rate of rivaroxaban use in gynecologic oncology patients at our institution highlights the need for larger, well-designed randomized controlled trials to confirm the safety and efficacy of its use in this population.

Topics: Academic Medical Centers; Adult; Aged; Anticoagulants; Drug Substitution; Enoxaparin; Factor Xa Inhibitors; Female; Genital Neoplasms, Female; Hemorrhage; Humans; Middle Aged; Pilot Projects; Recurrence; Retrospective Studies; Rivaroxaban; Secondary Prevention; Venous Thromboembolism; Warfarin

To assess the association between rivaroxaban and warfarin and major bleeding risk in unprovoked venous thromboembolism (VTE) patients.. Using US MarketScan claims from 1/2012-12/2016, we identified patients who had ≥1 primary hospitalization/emergency department visit diagnosis code for an unprovoked VTE, newly initiated on rivaroxaban or warfarin within 30 days after the VTE and ≥12 months of insurance coverage prior to the VTE. Differences in baseline covariates were adjusted using inverse-probability-of-treatment weights based on propensity scores (residual absolute standardized differences <0.1 achieved for all covariates). Endpoints included any major, gastrointestinal, genitourinary, intracranial, and other bleeds. Patients were followed for up to 12 months or until endpoint occurrence, index oral anticoagulant discontinuation/switch, insurance disenrollment or end of follow-up.. We identified 10 489 rivaroxaban and 26 364 warfarin patients with an unprovoked VTE. Upon Cox regression, rivaroxaban reduced patients' hazard of major bleeding by 27% (95% confidence interval [CI] = 8%-42%), gastrointestinal bleeding by 38% (95% CI = 14%-55%), and intracranial hemorrhage by 81% (95% CI = 41%-99%) vs warfarin. No subtype of major bleeding occurred statistically more often in rivaroxaban vs warfarin-treated patients.. Rivaroxaban was associated with a reduced risk of overall, gastrointestinal, and intracranial major bleeding vs warfarin in unprovoked VTE. No bleeding subtype was significantly more frequent in rivaroxaban patients.

Topics: Aged; Anticoagulants; Cohort Studies; Comorbidity; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Population Surveillance; Proportional Hazards Models; Risk Assessment; Risk Factors; Rivaroxaban; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients' demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients' demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p < 0.001). The efficacy and safety of Xa inhibitors as VTE treatment were comparable between cancer and non-cancer patients, and in elderly and non-elderly patients. This suggests that Xa inhibitors may be promising drugs for VTE treatment, irrespective of age and comorbid cancer.

Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Japan; Lower Extremity; Male; Middle Aged; Neoplasms; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism

The non-interventional XALIA study compared the safety and effectiveness of rivaroxaban with standard anticoagulation for the treatment of venous thromboembolism in routine clinical practice. This substudy assessed the effect of treatment with rivaroxaban on healthcare resource use, hospital length of stay (LOS) and frequency of hospitalisation.. In XALIA, patients aged ≥18 years scheduled to receive ≥3 months of rivaroxaban or standard anticoagulation treatment for deep vein thrombosis (DVT) were eligible. Treatment decisions were at the physician's discretion. Healthcare resource use, including hospital admission for the index DVT and initial LOS, was documented. The main analyses in this substudy were conducted in a 1:1 propensity score-matched set (PMS) of patients, with adjustment for cancer at baseline.. In the PMS analysis, 1124 rivaroxaban-treated patients and 1124 standard anticoagulation-treated patients were included. Baseline characteristics were similar between groups (mean age 60.8 years vs. 61.2 years, DVT only rates of 89.7% vs. 90.2% and cancer rates of 8.4% vs. 8.5%, respectively). Of these, 433/1124 (38.5%) rivaroxaban-treated patients and 438/1124 (39.0%) standard anticoagulation-treated patients were hospitalised. Index event LOS in the PMS analysis was a least-squares mean of 2.6 days shorter with rivaroxaban vs. standard anticoagulation (5.4 vs. 8.0 days; geometric means ratio = 0.67 [95% confidence interval 0.61-0.74, P < 0.001]).. In XALIA, hospital LOS was shorter with rivaroxaban than with standard anticoagulation, consistent with the phase III study results. DVT treatment with rivaroxaban in routine clinical practice may reduce the cost per patient vs. standard anticoagulation.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Europe; Female; Health Resources; Humans; Length of Stay; Male; Middle Aged; Patient Readmission; Propensity Score; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Oral anticoagulation (OAC) prescribed to AF patients for the prevention of cardioembolic complications likely has the added benefit of preventing venous thromboembolism (VTE). This study evaluated, among AF patients who are anticoagulated, whether type of OAC was associated with subsequent VTE risk.. Non-valvular AF patients prescribed OACs between 2010 and September 2015 were identified via the MarketScan administrative claims databases. OACs included warfarin and direct OACs (DOACs: dabigatran, rivaroxaban, and apixaban). Incident VTE was defined by ICD-9-CM codes. Patients were matched on age, sex, CHA. In total, 1357 VTE events accrued over a mean follow-up of 484 days. In multivariable-adjusted, propensity score-matched Cox models, relative to new users of warfarin, risk of incident VTE was lower among new users of dabigatran [hazard ratio (95% confidence interval) = 0.55 (0.47-0.66)] and apixaban [0.51 (0.39-0.68)], but similar among new users of rivaroxaban [1.01 (0.87-1.19)]. In head-to-head DOAC comparisons, VTE risk was lower among users of dabigatran [0.48 (0.36-0.64)] and apixaban [0.61 (0.47-0.78)] vs rivaroxaban. Findings were mostly similar across patient sub-groups.. In this large practice-based population of AF patients prescribed OACs for primary prevention of stroke and systemic embolization, subsequent risk of VTE was lowest among those prescribed apixaban and dabigatran, while risk was similar with prescriptions for warfarin and rivaroxaban. Among AF patients prescribed OACs, lowering the risk of VTE may be an additional benefit of apixaban and dabigatran, beyond the reduced bleeding risk observed in randomized clinical trials.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Oral anti-Xa inhibitors have demonstrated noninferiority to vitamin K antagonists (VKAs) for the prevention of stroke in patients with atrial fibrillation and recurrent venous thromboembolism. They are associated with a decrease in major bleeding. In contrast with VKA, no coagulation monitoring is required. However, in clinical practice, determination of drug concentration is sometimes necessary.. The objective of this study was to evaluate a low-molecular-weight heparin (LMWH) calibrated anti-Xa assay for the quantification of rivaroxaban and apixaban plasma concentration in emergency.. The anti-Xa plasma concentration of rivaroxaban and apixaban were measured in emergency in 210 patients using STA anti-Xa liquid assay. For each plasma concentration <150 ng/mL of rivaroxaban or apixaban, an anti-Xa assay calibrated with LMWH was performed.

Topics: Aged; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Calibration; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Predictive Value of Tests; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Sensitivity and Specificity; Stroke; Venous Thromboembolism

This study examined potential differences in bleeding between apixaban and rivaroxaban, the most commonly utilized direct oral anticoagulants at the Richard L. Roudebush VA Medical Center. Additionally, the analysis included a comparison between observed and literature-reported bleeding rates. This retrospective chart review examined 452 (39%) Veterans receiving rivaroxaban and 716 (61%) Veterans receiving apixaban. Bleeding rates were expressed per 100 patient-years and the overall rates were analyzed as the primary analysis. Secondary objectives included comparisons based on indication and severity, as well as comparisons to literature-reported bleed rates, time to bleeding event, and location of the bleed. The analysis did not detect any statistically significant differences between apixaban and rivaroxaban in terms of overall, (ARR 0.90% per 100 patient-years, 95% CI - 0.58 to 2.38%, p > 0.05) major, (ARR 0.22% per 100 patient-years, 95% CI - 0.74 to 1.17%, p > 0.05) or non-major clinically relevant (ARR 0.35% per 100 patient-years, 95% CI - 0.57 to 1.27%, p > 0.05) bleeding. Observed bleeding for both rivaroxaban and apixaban in the Veteran population exceeded the rates reported by the literature when used for atrial fibrillation (1.96% vs. 0.15%, p < 0.05; 1.08% vs. 0.16%, p < 0.05) but the opposite was seen for long term venous thromboembolism (VTE) treatment (3.97% vs. 8.03%, p < 0.0001; 0.14% vs. 15.51%, p < 0.0001) or extended VTE prophylaxis (0.07% vs 5.98%, p < 0.0001; 0.07% vs 1.88%, p < 0.01). Results from this study suggest these agents impart similar levels of risk, but variations in bleeding risk between the Veteran population and the patients in the original clinical trials may exist.

Topics: Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Blood Coagulation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; United States; United States Department of Veterans Affairs; Venous Thromboembolism; Veterans Health

Topics: Aged; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Insurance; Middle Aged; Neoplasms; Recurrence; Risk; Rivaroxaban; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Humans; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Apixaban and rivaroxaban, both direct-acting oral anticoagulants, are being increasingly used in routine clinical practice because of their fixed dosing and favourable pharmacological profiles. Differences in the risk of recurrent venous thromboembolism and major bleeding events between the two drugs are currently unknown. We aimed to compare the effectiveness and safety of apixaban and rivaroxaban in prevention of recurrent venous thromboembolism and major bleeding events in patients with venous thromboembolism.. We did a retrospective cohort analysis of data from the Truven Health MarketScan commercial and Medicare Supplement claims databases in the USA. We analysed data for adult patients with newly diagnosed venous thromboembolism (deep vein thrombosis or pulmonary embolism) who were new users of apixaban or rivaroxaban between Jan 1, 2014, and Dec 31, 2016. Patients who did not initiate the study drugs within 30 days of their diagnosis, those without 12 months of continuous enrolment in medical and pharmacy benefits, and those who used other anticoagulants during the baseline period were excluded. The primary effectiveness outcome was the incidence of recurrent venous thromboembolism and the primary safety outcome was the incidence of major bleeding events. Cox-proportional hazard models after propensity score matching were used to calculate the hazard ratio (HR) and 95% CI.. After propensity score matching, 15 254 patients were included in the cohort (3091 apixaban users and 12 163 rivaroxaban users). The crude incidence of recurrent venous thromboembolism was three per 100 person-years in the apixaban group and seven per 100 person-years in the rivaroxaban group. The incidence of major bleeding was three per 100 person-years in the apixaban group and six per 100 person-years in the rivaroxaban group. In multivariable Cox regression models, the use of apixaban compared with rivaroxaban was associated with decreased risk of recurrent venous thromboembolism (HR 0·37 [95% CI 0·24-0·55]; p<0·0001) and major bleeding events (0·54 [0·37-0·82]; p=0·0031).. Based on our findings, apixaban seems to be more effective than rivaroxaban in preventing the development of recurrent venous thromboembolism and major bleeding events. Our data might give some assurance to clinicians that apixaban can be an effective and safe therapeutic option for treatment of patients with venous thromboembolism.. None.

Topics: Anticoagulants; Cohort Studies; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

The highest risk of adverse events for patients with acute venous thromboembolism (VTE) is during the early anticoagulation period. However, no established model exists for early clinical monitoring of patients treated with non-vitamin K antagonist oral anticoagulants (NOACs). The authors' aim was to evaluate the utility of a nurse-led pathway to minimize adverse events in acute VTE patients starting on rivaroxaban. The rivaroxaban VTE treatment pathway is a prospective cohort study of consecutive patients with objectively confirmed VTE between July 2015 and May 2017. Primary outcome was the proportion of patients identified at major risk of adverse events (bleeding or recurrent VTE). Secondary outcomes were rates of interventions, major or clinically relevant nonmajor bleeding (CRNMB), recurrent VTE, and all-cause mortality at 90 days. Among 304 participants, 5% (

Topics: Acute Disease; Adult; Aged; Critical Pathways; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Monitoring, Physiologic; Nurse-Patient Relations; Outcome Assessment, Health Care; Prospective Studies; Recurrence; Risk Factors; Rivaroxaban; Venous Thromboembolism

We sought to evaluate the real-world effectiveness and safety of prolonged anticoagulation with rivaroxaban following a provoked venous thromboembolism.. Using US MarketScan claims from November 2012 to March 2017, we identified adults with ≥1 primary hospitalization or emergency department diagnosis code for venous thromboembolism, a provoking (major or minor, persistent or transient) risk factor, at least 3 months of continuous rivaroxaban treatment, and ≥12 months of continuous insurance benefits prior to their qualifying venous thromboembolism. Patients were categorized as either continuing rivaroxaban or discontinuing anticoagulation (no anticoagulation or nonaspirin antiplatelet agents but may have received aspirin) after the initial 3 months of rivaroxaban treatment (index date). Differences in baseline covariates between cohorts were adjusted for using inverse probability-of-treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Twelve month incidences of recurrent venous thromboembolism or major bleeding were compared between cohorts using Cox regression (according to an intention-to-treat methodology) and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).. Among patients experiencing a provoked venous thromboembolism and treated with rivaroxaban for the first 3 months (N=4,990), continued rivaroxaban use beyond 3 months (median [25%, 75% range duration of additional rivaroxaban use = 3 [2, 5] months) was associated with a 44% (95% CI of 9%-66%) lower hazard of recurrent venous thromboembolism without altering major bleeding risk [HR of 0.87, 95% CI of 0.51-1.49] versus anticoagulation discontinuation (with or without aspirin use).. Our study suggests continuing rivaroxaban after the initial 3 month period was associated with a decreased risk of recurrent venous thromboembolism. The observed reduction in recurrent venous thromboembolism with prolonged rivaroxaban use was not associated with a significant change in major bleeding risk.

Topics: Aged; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Rivaroxaban; Secondary Prevention; Venous Thromboembolism

Non-vitamin K antagonist oral anticoagulants (NOACs) have been included in international guidelines as important alternatives to vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) and stroke prevention in non-valvular atrial fibrillation (NVAF). Meanwhile, in the Netherlands, NOACs are widely used next to VKAs. The objective of this study is to estimate the cost-effectiveness of treatment with rivaroxaban compared to VKAs in NVAF and VTE patients in the Netherlands, using data from international prospective observational phase IV studies.. Two models were developed to represent NVAF and VTE patients, populated with patients from the XANTUS (NCT01606995) and XALIA (NCT01619007) international prospective observational studies. The 1-year cost-effectiveness of rivaroxaban use, compared to VKAs, was explored in a population consisting of NVAF and VTE patients (base case) as well as for four scenarios with sub-populations: NVAF patients only, VTE patients only, NVAF patients with unstable international normalized ratio (INR), and NVAF patients using an INR self-measuring device.. In the base case, rivaroxaban saved €72,350 and gained 21 quality-adjusted life-years (QALYs) in a simulation of 2,000 patients over the use of VKAs. Ergo, rivaroxaban was dominant over VKAs. The probabilistic sensitivity analysis showed a probability of 85% for rivaroxaban being dominant and 100% at a willingness-to-pay threshold of €20,000/QALY. Rivaroxaban appeared to be dominant in all scenarios as well, except for the NVAF-patients-only scenario where the incremental cost-effectiveness ratio (ICER) was €157/QALY.. In patients with NVAF or VTE, rivaroxaban treatment is likely to be cost-effective and a potentially cost-saving alternative to VKA in the Netherlands.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Cost-Benefit Analysis; Female; Health Expenditures; Health Resources; Humans; Male; Models, Econometric; Netherlands; Prospective Studies; Rivaroxaban; Severity of Illness Index; Venous Thromboembolism; Vitamin K

Venous thromboembolic disease (VTE) is a complication not uncommon following total knee arthroplasty. Postoperative bleeding-related complications are a concern in many guidelines. The authors aimed to compare the amount of postoperative drainage from closed suction drainage, transfusion rate, and postoperative complications between aspirin and rivaroxaban as VTE prophylaxes after total knee arthroplasty.. This study was a retrospective case-matched study of 155 patients. The data were collected between 2008 and 2015 from patients who had total knee arthroplasty using aspirin or rivaroxaban as the VTE prophylaxis. Seventy-nine patients received aspirin, and 76 patients received rivaroxaban. A single surgeon operated on all patients with the same surgical technique and patient care protocol.. The total closed suction drainage outputs at 48 h were not significantly different between the aspirin and rivaroxaban groups (p = 0.10). Eighteen percent of patients in the aspirin group and 25% of patients in the rivaroxaban group received blood transfusions (p = 0.37). There were no bleeding-related complications or VTE in either group.. Aspirin and rivaroxaban were effective and safe as VTE chemoprophylaxis in total knee arthroplasty.

Topics: Aged; Arthroplasty, Replacement, Knee; Aspirin; Blood Transfusion; Chemoprevention; Drainage; Factor Xa Inhibitors; Female; Humans; Male; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thromboembolic events including venous thromboembolism (VTE) in association with the presence of antiphospholipid antibodies. The standard treatment of VTE historically consists of anticoagulation therapy with warfarin, a vitamin K antagonist. Recently, direct oral anticoagulants, including rivaroxaban have become available for the treatment of VTE. However, the choice of anticoagulant, and the duration of anticoagulation in patients with APS has not been determined yet due to lack of evidence. Here, we report a case of recurrent venous thrombosis after discontinuation of rivaroxaban therapy and avoiding sedentary lifestyle in a patient with APS. We suggest that indefinite anticoagulation therapy might be needed even in low-risk APS cases.

Topics: Aftercare; Antiphospholipid Syndrome; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Pulmonary Embolism; Recurrence; Rivaroxaban; Tomography, X-Ray Computed; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The clinical profile, evolution and complications of treatment with rivaroxaban in a cohort of patients presenting with venous thromboembolism (VTE) were analyzed in an observational, non-interventional and prospective study.A total of 111 patients were included in the study. Clinical data were collected from the medical history of the patients and recorded in a specific database.Mean age was 63.8 ± 17.4 years, 53.2% of patients were men, 55.9% had at least another concomitant condition, and 40.9% at least 1 VTE risk factor. 54.1% of patients presented with deep venous thrombosis, 32.4% with pulmonary embolism and 13.5% with both conditions simultaneously. The 61% of patients were admitted to hospital and mean hospital length-of-stay was 8.8 ± 9.9 days. After a mean follow-up 530 ± 464 days (median follow-up of 405 days), 3.9% of patients died and VTE recurrence occurred in 2.9% of patients. While receiving rivaroxaban, a first bleeding complication occurred in 8.1%; all events were minor bleeding.Our study supports the current literature data and confirms the similar results of real-life VTE patients with those enrolled in the rivaroxaban pivotal clinical trials. Rivaroxaban may facilitate outpatient treatment and might be considered as a first-line therapy for the management of VTE patients.

Topics: Aged; Factor Xa Inhibitors; Female; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Many strategies for venous thromboembolism (VTE) prophylaxis following hip and knee arthroplasty exist, with extensive controversy regarding the optimum strategy to minimize risk of VTE and bleeding complications. Data from the American Board of Orthopedic Surgery Part II (oral) Examination case list database was analyzed to determine efficacy, complication rates, and prescribing patterns for different prophylactic strategies.. The American Board of Orthopedic Surgery case database was queried utilizing Current Procedural Terminology codes 27447 and 27130 for primary total knee and hip arthroplasty, respectively. Geographic region, patient age, gender, deep vein thrombosis prophylaxis strategy, and complications were obtained. Less aggressive prophylaxis patterns were considered if only aspirin and/or sequential compression devises were utilized. More aggressive VTE prophylaxis patterns were considered if any of low-molecular-weight heparin (enoxaparin), warfarin, rivaroxaban, fondaparinux, or other strategies was used.. In total, 22,072 cases of primary joint arthroplasty were analyzed from 2014 to 2016. The national rate of less aggressive VTE prophylaxis strategies was 45.4%, while more aggressive strategies were used in 54.6% of patients. Significant regional differences in prophylactic strategy patterns exist between the 6 regions. The predominant less aggressive prophylaxis pattern was aspirin with sequential compression devises at 84.8% with 14.8% receiving aspirin alone. Use of less aggressive prophylaxis strategy was significantly associated with patients having no complications (95.5% vs 93.0%). Use of more aggressive prophylaxis patterns was associated with higher likelihood of mild thrombotic (0.9% vs 0.2%), mild bleeding (1.3% vs 0.4%), moderate thrombotic (1.2% vs 0.4%), moderate bleeding (2.7% vs 2.1%), severe thrombotic (0.1% vs 0.0%), severe bleeding events (1.2% vs 0.9%), infections (1.9% vs 1.3%), and death within 90 days (0.7% vs 0.3%). Similar results were found in subgroup analysis of total hip and knee arthroplasty patients.. It was not possible to ascertain the individual rationale for use of more aggressive VTE prophylaxis strategies; however, more aggressive strategies were associated with higher rates of bleeding and thrombotic complications. Less aggressive strategies were not associated with a higher rate of thrombosis.. Therapeutic Level III.. All views expressed in the study are the sole views of the authors and do not represent the views of the American Board of Orthopedic Surgery.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Databases, Factual; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Orthopedic Procedures; Orthopedics; Practice Patterns, Physicians'; Risk Factors; Rivaroxaban; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

The increasing incidence of venous thromboembolism (VTE) in paediatric population has stimulated the development of liquid anticoagulant formulations. Thus our goal is to formulate a liquid formulation of poorly-water soluble anticoagulant, rivaroxaban (RIVA), for paediatric use and to assess the possibility of its intravenous administration in emergencies. Self-nanoemulsifying drug delivery systems (SNEDDSs) were developed and characterized. SNEDDS constituents were estimated from the saturated solubility study followed by plotting the corresponding ternary phase diagrams to determine the best self-emulsified systems. Thermodynamic stability, emulsification, dispersibility, robustness to dilution tests,

Topics: Animals; Anticoagulants; Biological Availability; Chemistry, Pharmaceutical; Drug Liberation; Drug Stability; Emergencies; Emulsions; Humans; Models, Animal; Nanocapsules; Particle Size; Polyethylene Glycols; Polymers; Polysorbates; Propylene Glycols; Rats; Rheology; Rivaroxaban; Solubility; Surface Properties; Venous Thromboembolism; Water

Rivaroxaban is a substrate for ABCB1 transporter and is commonly used in patients undergoing hip or knee replacement surgery for thromboprophylaxis. The objective of this study was to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model to investigate the influence of ABCB1 gene expression and polymorphism on rivaroxaban exposure and anticoagulation effects.. Five blood samples per patient were collected during 5 days after the surgery for the determination of rivaroxaban concentration in plasma and for determination of prothrombin time and partial thromboplastin time. Non-linear mixed effects model was used for a population PK-PD analysis and for testing covariate effects.. A one-compartment PK model with first-order absorption adequately described the pharmacokinetic data. The typical oral clearance (CL/F) was 6.12 L/h (relative standard error, 15.8%) and was associated with ABCB1 expression. Compared to base line before the surgery, a significant ABCB1 downregulation was observed 5 days after the surgery (p < 0.001). Prothrombin time and partial thromboplastin time were both linearly associated to the logarithm of the rivaroxaban plasma concentration.. We confirmed that variable rivaroxaban CL/F is associated with ABCB1 expression, which is in accordance with previous studies on P-glycoprotein involvement in rivaroxaban PK. Furthermore, we observed the downregulation of ABCB1 expression after the surgery. The cause remains unclear and further research is needed to explain the underlying mechanisms.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; ATP Binding Cassette Transporter, Subfamily B; Down-Regulation; Factor Xa Inhibitors; Female; Genotype; Humans; Male; Middle Aged; Models, Biological; Polymorphism, Single Nucleotide; Postoperative Period; Rivaroxaban; Venous Thromboembolism

To compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE).. Consecutive patients enrolled in the Mayo Thrombophilia Clinic Registry (between March 1, 2013, and January 30, 2018) and treated with apixaban or rivaroxaban for acute VTE were followed forward in time. The primary efficacy outcome was VTE recurrence. The primary safety outcome was major bleeding; the second safety outcome was clinically relevant nonmajor bleeding (CRNMB); and the third was a composite of major bleeding or CRNMB.. Within the group of 1696 patients with VTE enrolled, 600 (38%) were treated either with apixaban (n=302, 50%) or rivaroxaban (n=298, 50%) within the first 14 days of VTE diagnosis and who completed at least 3 months of therapy or had a study event. Recurrent VTE was diagnosed in 7 patients (2.3%) treated with apixaban and in 6 (2%) treated with rivaroxaban (adjusted hazard ratio [aHR], 1.4; 95% CI, 0.5-3.8). Major bleeding occurred in 11 patients (3.6%) receiving apixaban and in 9 patients (3.0%) receiving rivaroxaban (aHR, 1.2; 95% CI, 0.5-3.2). Clinically relevant nonmajor bleeding was diagnosed in 7 patients (2.3%) receiving apixaban and in 20 (6.7%) receiving rivaroxaban (aHR, 0.4; 95% CI, 0.2-0.9). The rates of composite major bleeding or CRNMB were similar (aHR, 0.6; 95% CI, 0.3-1.2). Most study events occurred in patients with cancer.. In the setting of a standardized, guideline-directed, patient-oriented clinical practice, the efficacy and safety of apixaban and rivaroxaban for the treatment of acute VTE were comparable.

Topics: Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Background Direct oral anticoagulants (DOACs) cause false positive lupus anticoagulant (LA) results. We assessed the impact of DOAC-Stop, reversing in vitro effects of DOACs, on LA testing in anticoagulated patients. Methods We assessed 75 venous thromboembolism patients aged 44.5±14.6 years. Blood samples were collected 2-28 h since intake of DOACs, including 50 patients on rivaroxaban, 20 on dabigatran and five on apixaban. LA testing was performed at baseline and after DOAC-Stop treatment. Positive LA was defined as the normalized (patient/standard plasma clotting time) LA screening and screening (LA1)/confirmation (LA2) ratios exceeding 1.2. Results LA diluted Russell's viper venom time (dRVVT) normalized screening test revealed abnormal results in 73 (97.3%) and activated partial thromboplastin time (APTT)-LA in 49 (65.3%) patients. In six (8%) patients, antiphospholipid syndrome (APS) was diagnosed. dRVVT LA1/LA2 was abnormal in 35 (50.7%) patients taking DOACs. The APTT ratio was normal in all studied subjects. DOAC-Stop completely removed dabigatran and reduced by 98% rivaroxaban and by 92.3% apixaban concentrations (all p<0.05). After DOAC-Stop screening dRVVT remained prolonged in 34 (49.3%) patients (p<0.001), while dRVVT LA1/LA2 was abnormal in six (8.7%) subjects, with no association with DOAC concentrations at baseline and after DOAC-Stop. The APTT-LA screening test remained prolonged in five (7.2%) patients, while the APTT LA1/LA2 ratio was normal in those subjects. DOAC-Stop did not influence LA testing in APS patients. Conclusions Application of DOAC-Stop effectively reduced plasma DOAC concentrations leading to appropriate dRVVT results in up to 97% of VTE patients.

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; Dabigatran; Factor Xa Inhibitors; False Positive Reactions; Female; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Partial Thromboplastin Time; Plasma; Prothrombin Time; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Rivaroxaban could be an attractive alternative to low molecular weight heparin for the treatment of cancer-associated venous thromboembolism (VTE) but the safety and effectiveness remain unclear. We examined risk of recurrent VTE and major bleeding associated with rivaroxaban treatment of cancer-associated VTE.. Through linkage of nationwide Danish registries, we identified all adults with cancer-associated VTE initiating treatment with rivaroxaban, 2012-2017. We estimated rates and absolute risk of the primary outcome of recurrent VTE and major bleeding; all-cause mortality was studied as a secondary outcome.. We identified 8901 patients with cancer-associated VTE of whom 476 (5.3%) redeemed a prescription for rivaroxaban within 30 days of VTE diagnosis (mean age 71.5 years, 41% females, 57% with pulmonary embolism). Median time from cancer diagnosis to rivaroxaban prescription was 31 days (interquartile range 12-73 days). Most frequent cancers were gastrointestinal (26.1%), genitourinary (23.3%), and hematological cancer (12.6%). Few had distant metastases (7.1%). At 6 months, recurrent VTE occurred in 6.1% (15.1 events per 100 person-years) with the highest absolute risks for genitourinary cancer (8.1%), gastrointestinal cancer (7.3%), and breast cancer (6.5%). Major bleeding occurred in 1.9% (5.3 events per 100 person-years), in particular, in genitourinary cancer (4.5%) and lung cancer (4.2%). Eighty deaths (17.8%) occurred during follow up.. In this clinical practice setting, rivaroxaban was rarely used for cancer-associated VTE. However, among those who received rivaroxaban, the treatment appeared safe and effective with rates comparable to previous studies of selected populations.

Topics: Aged; Cohort Studies; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Neoplasm Recurrence, Local; Neoplasms; Risk Factors; Rivaroxaban; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are safe and efficacious when compared to warfarin for patients with venous thromboembolism (VTE). However, bleeding is a major side effect of anticoagulant therapy in VTE patients. Discontinuation of the DOACs associated to adverse events such as bleeding. The HAS-BLED score predicts warfarin-associated hemorrhage. However, little is known about risk factors for DOAC-associated minor bleeding in VTE patients. We aimed to identify risk factors for minor bleeding in VTE patients that were treated with edoxaban, rivaroxaban, or apixaban. We retrospectively evaluated the data of 212 VTE patients who received treatment with a DOAC. The study endpoint was defined as the occurrence of minor bleeding. Logistic regression analysis was used to determine risk factors that were significantly associated with minor bleeding. A total of 36 (17.0%) patients experienced minor bleeding, with rates of 15.7%, 0%, and 21.3% for edoxaban, rivaroxaban, and apixaban, respectively. In the multivariate analysis, bleeding history or predisposition [odds ratio (OR) 6.083, 95% confidence interval (CI) 2.131-17.364, p=0.001] and cancer (OR 6.397, 95% CI 2.858-14.317, p<0.001) were significantly associated with minor bleeding. Bleeding history or predisposition and cancer were the most important risk factors for DOAC-induced minor bleeding in VTE patients in this study. To continue anticoagulant therapy of the DOACs, further management systems by minor bleeding risk factors for patients with VTE will be required.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Severity of Illness Index; Thiazoles; Venous Thromboembolism

We aimed to evaluate the efficacy and safety of rivaroxaban in thromboprophylaxis compared with those of aspirin in real-world patients who underwent hip arthroplasty using nationwide claims data.. Patients aged more than or equal to 18 years with at least one hip arthroplasty including total and partial hip replacements and hip replacement revisions during July 2009 to June 2013 were identified from the Health Insurance Review and Assessment (HIRA) database. The study outcome was incidence rate of thromboembolic events and anticoagulation-related major bleeding within 90 days of hip arthroplasty.. The incidence of overall venous thromboembolism (VTE) within 90-day postsurgery was significantly higher in the aspirin cohort than it was in the rivaroxaban cohorts. Bleeding events associated with pharmacological thromboprophylaxis in patients who received rivaroxaban were not significantly different from that in aspirin-treated patients. In aspirin cohorts, 65.7% of patients received less than 3-week treatment while about half received a less than 14-day treatment, and 31.7% received more than 3-week treatment in the rivaroxaban cohort.. This study demonstrates that rivaroxaban was more effective in preventing VTE following hip arthroplasty without raising bleeding risks in clinical settings. Age more than or equal to 80 years, women, and a history of thromboembolism were the risk factors of VTE incidence.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Female; Follow-Up Studies; Humans; Incidence; Male; Medical History Taking; Middle Aged; Postoperative Hemorrhage; Republic of Korea; Risk Factors; Rivaroxaban; Sex Factors; Treatment Outcome; Venous Thromboembolism

Rivaroxaban, a direct oral anticoagulant, has demonstrated non-inferiority to warfarin for venous thromboembolism (VTE) treatment in clinical trials. This study aimed to analyze the direct medical costs for VTE management with rivaroxaban versus warfarin in Hong Kong Chinese patients.. In this retrospective observational study, VTE patients admitted to the Princess Margaret Hospital from March 2012 to February 2017 who were initiated and discharged with either rivaroxaban or warfarin were included. Patient demographic and clinical data, and healthcare resource utilization for VTE management were collected for the VTE index admission and 1-year post-discharge period.. A total of 181 patients (90 in the rivaroxaban group; 91 in the warfarin group) were included. The mean (± SD) length of stay (LOS) was 4.8 ± 2.7 days and 8.0 ± 3.0 days in the rivaroxaban and warfarin groups, respectively (p > 0.001). The total cost for VTE index admission in the rivaroxaban group was significantly lower than that of the warfarin group (USD 5473 ± 1914 versus USD 3457 ± 1796; p < 0.001) (USD 1 = HKD 7.8). Recurrent VTE and bleeding rates in 1-year post-discharge period were not significantly different between the two groups. The direct total cost of the rivaroxaban group (USD 1271 ± 767) was significantly lower than that of the warfarin group (USD 1739 ± 1045) in 1-year post-discharge period (p < 0.001).. Total direct cost and LOS for VTE admission and total cost in 1-year post-discharge period were significantly lower in patients initiated and discharged with rivaroxaban than those of warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cost Savings; Cost-Benefit Analysis; Drug Costs; Factor Xa Inhibitors; Female; Hemorrhage; Hong Kong; Hospital Costs; Hospitalization; Humans; Male; Middle Aged; Models, Economic; Recurrence; Retrospective Studies; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism; Warfarin

Topics: Humans; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Humans; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Humans; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Essentials Factor Xa (FXa)-targeting direct oral anticoagulants (DOACs) reduce venous thromboembolism (VTE) The effects of FXa-targeting DOACs on cancer progression remain to be studied In xenograft models, a FXa-targeting DOAC did not inhibit breast cancer growth and metastasis A thrombin-targeting DOAC, dabigatran, also did not inhibit breast cancer growth and metastasis ABSTRACT: Background Factor Xa-targeting DOACs were recently found to reduce recurrent VTE efficiently in cancer patients when compared to the standard treatment with low-molecular-weight heparins (LMWHs). While the anticancer effects of LMWHs have been extensively studied in preclinical cancer models, the effects of FXa-targeting DOACs on cancer progression remain to be studied. Objective We investigated whether the FXa-targeting DOAC rivaroxaban and the thrombin-targeting DOAC dabigatran etexilate (DE) affected human breast cancer growth and metastasis in orthotopic xenograft models. Methods/results Mice that were put on a custom-made chow diet supplemented with rivaroxaban (0.4 or 1.0 mg/g diet) or dabigatran etexilate (DE) (10 mg/g diet) showed prolonged ex vivo coagulation times (prothrombin time [PT] and activated partial thromboplastin time [aPTT] assay, respectively). However, rivaroxaban and DE did not inhibit MDA-MB-231 tumor growth and metastasis formation in lungs or livers of 7-week-old fully immunodeficient NOD/SCID/ƴ

Topics: Animals; Anticoagulants; Antithrombins; Breast Neoplasms; Cell Line, Tumor; Dabigatran; Disease Progression; Factor Xa Inhibitors; Female; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Metastasis; Rivaroxaban; Triple Negative Breast Neoplasms; Venous Thromboembolism; Xenograft Model Antitumor Assays

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Humans; Peer Review; Physiatrists; Rivaroxaban; Venous Thromboembolism

Direct oral anticoagulants (DOACs) are being increasingly used. However, unlike warfarin, less is known regarding their long-term side effects. To better evaluate the rates of DOAC-related adverse events (AEs) on a population level, we examined AEs reported to the FDA for three commonly used DOACs and warfarin.. We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles reported drug-related AEs from 1969 onwards. The safety profiles of the included drugs were assessed by comparing AEs per outpatient prescription and with proportional reporting ratios (PRR).. Rivaroxaban had the highest proportion of reported AEs. Most notably the rate for breakthrough venous thromboembolism (VTE) was higher than other DOACs. Dabigatran had the highest reported rates of ischemic stroke. When the DOAC data were analyzed using PRR, reported rates of VTE were again higher with rivaroxaban while dabigatran again showed slightly higher than expected rates of ischemic stroke. Apixaban did not show higher than expected rates in any category.. Our analysis found rates of reported breakthrough VTE were significantly higher with rivaroxaban, while apixaban had no higher than expected rates of any studied AEs.

Topics: Administration, Oral; Ambulatory Care; Anticoagulants; Databases, Factual; Drug Prescriptions; Humans; Mandatory Reporting; Rivaroxaban; United States; United States Food and Drug Administration; Venous Thromboembolism

Denser fibrin structure and impaired fibrinolysis reported in patients following venous thromboembolism (VTE) can predict recurrent VTE after cessation of anticoagulation.. The aim of the study was to investigate whether the properties of fibrin clot may be useful in predicting adverse events in patients with VTE receiving rivaroxaban.. In 132 patients with VTE treated with rivaroxaban for 8 weeks or longer, we determined plasma clot permeability (Ks) and clot lysis time (CLT) in blood samples collected 2 to 28 hours after rivaroxaban intake (20 mg/d). The primary endpoint was a composite of major and clinically relevant nonmajor bleeding, while the secondary endpoint was recurrent symptomatic VTE.. During a median follow‑ up of 32 months, the annual rates of primary and secondary endpoints were 3.6% and 2.7%, respectively. There were no differences in Ks and CLT between individuals who experienced the primary endpoint and the remainder. Patients with recurrent VTE had lower baseline Ks (-26.7%) and prolonged CLT (+20.8%) on rivaroxaban, without differences in rivaroxaban concentrations at the time of blood collection. After adjustment for confounding factors, Ks was the only predictor of VTE recurrence on rivaroxaban (odds ratio, 0.23; 95% CI, 0.06-0.94).. Our study suggests that Ks assessed on rivaroxaban may provide prognostic information about the risk of recurrent VTE in anticoagulated patients.

Topics: Adult; Blood Coagulation; Cohort Studies; Factor Xa Inhibitors; Female; Fibrin Clot Lysis Time; Humans; Male; Middle Aged; Permeability; Rivaroxaban; Venous Thromboembolism; Young Adult

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Health Expenditures; Health Resources; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Insurance Claim Review; Male; Middle Aged; Neoplasms; Patient Acceptance of Health Care; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Because studies of direct oral anticoagulants in patients with venous thromboembolism and non-valvular atrial fibrillation have had minimal representation of morbidly obese patients (ie, body-mass index [BMI] ≥40 kg/m. We did a single-centre, retrospective analysis of chart data for all adult patients aged at least 18 years at Montefiore Medical Center (Bronx, NY, USA) with a BMI of at least 40 kg/m. We obtained data for 795 patients: 150 prescribed apixaban, 326 rivaroxaban, and 319 warfarin. In 366 patients prescribed an anticoagulant for venous thromboembolism, the incidence of recurrent venous thromboembolism was similar between the apixaban, rivaroxaban, and warfarin cohorts (1/47 [2·1%, 95% CI 0·0-6·3], 3/152 [2·0%, 0·0-4·2], and 2/167 [1·2%, 0·0-2·9], respectively; p=0·74). Incidence of major bleeding in this patient group was also similar between the treatment cohorts (1/47 patients on apixaban [2·1%, 95% CI 0·0-6·3], 2/152 on rivaroxaban [1·3%, 0·0-3·1], and 4/167 on warfarin [2·4%, 0·1-4·7]; p=0·77). In 429 patients prescribed an anticoagulant for atrial fibrillation, incidence of stroke was similar between the treatment cohorts (1/103 patients on apixaban [1·0%, 95% CI 0·0-2·9], 4/174 on rivaroxaban [2·3%, 0·1-4·5], and 2/152 on warfarin [1·3%, 0·0-3·1], p=0·71). In this patient group, major bleeding occurred in 3/103 patients on apixaban (2·9%, 95% CI 0·0-6·2), 5/174 on rivaroxaban (2·9%, 0·4-5·4), and 12/152 on warfarin (7·9%, 3·6-12·2); p=0·063. Time-to-event analyses showed that risk of all outcomes in patients with venous thromboembolism, and stroke and composite bleeding in patients with atrial fibrillation, were similar between the anticoagulant cohorts.. Our retrospective study provides further evidence of similar efficacy and safety between the direct oral anticoagulants apixaban and rivaroxaban, and warfarin in morbidly obese patients with atrial fibrillation and venous thromboembolism. These data, if confirmed in prospective studies, might enable patients with a BMI of at least 40 kg/m. None.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Body Mass Index; Factor Xa Inhibitors; Female; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Obesity, Morbid; Proportional Hazards Models; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE.. Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality.. Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (. Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.

Topics: Anticoagulants; Biliary Tract; Factor Xa Inhibitors; Female; Gastrointestinal Tract; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Retrospective Studies; Rivaroxaban; Stomach Neoplasms; Venous Thromboembolism

Low-molecular-weight heparins (LMWH) are the drug of choice for treatment of cancer-associated thrombosis (CAT), however non-vitamin K antagonist oral anticoagulants (NOAC) seem to be a reasonable alternative. We investigated the safety and efficacy of NOAC versus LMWH in patients with a history of CAT.. In a prospective cohort study 128 consecutive patients with active cancer who experienced CAT were enrolled following LMWH treatment for ≥3 months. Symptomatic recurrent venous thromboembolism (VTE), bleeding and death were recorded during follow-up.. 65 (50.8%) patients were switched to NOAC and 63 (49.2%) continued with LMWH. During a median follow-up of 17 (interquartile range, 15-21) months, recurrent VTE was observed in 6 (9.2%) patients on NOAC and in 12 (19.0%) on LMWH (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.16-1.16). The rate of major bleeding was 9.2% and 4.8%, respectively (HR 2.00, 95% CI 0.50-8.00). The median time to bleeding was shorter in patients on NOAC (3 [2.25-5.5] months) versus on LMWH (9 [6.5-13.0] months). The mortality rates were similar in both groups (15.4% versus 15.9%, respectively, HR 0.76, 95% CI 0.32-1.84).. In patients following CAT, extended treatment with NOAC, compared with LMWH, appears to be associated with similar effectiveness and safety.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Comparative Effectiveness Research; Dabigatran; Drug Administration Schedule; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Prospective Studies; Pyrazoles; Pyridones; Recurrence; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

Topics: Aspirin; Factor Xa Inhibitors; Hospitalization; Humans; Placebo Effect; Platelet Aggregation Inhibitors; Rivaroxaban; Thrombosis; Venous Thromboembolism

Topics: Cohort Studies; Humans; Permeability; Rivaroxaban; Thrombosis; Venous Thromboembolism

D-dimer levels measured during and after vitamin K antagonist withdrawal may be used in clinical practice to assess the individual risk of recurrent venous thromboembolism. Currently, direct oral anticoagulants (DOACs) are frequently used in venous thromboembolism treatment; however, their pharmacokinetics and pharmacodynamics characteristics are completely different than vitamin K antagonists. The present study aimed at comparing the results of D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with DOACs or warfarin.. D-dimer levels were measured in 527 patients ("cases") during DOACs treatment (T0) and after 15 (T15), 30 (T30), 60 (T60) and 90 (T90) days after their discontinuation and in 527 patients ("controls") enrolled in the DULCIS study (all treated with warfarin), matched for sex, age (+/-3 y), type of D-dimer assay and site of venous thromboembolism. Both cases and controls received anticoagulant treatment after a first venous thromboembolism event that was unprovoked or associated with weak risk factors.. The rate of positive D-dimer results was significantly higher in cases than in controls at T0 (10.8% vs 5.1%, p = 0.002) and at T30 (18.8% vs 11.8%, p = 0.019), as well as at the other time-points, though not statistically significant.. D-dimer levels during and after stopping an anticoagulant treatment for a venous thromboembolism episode differ between patients treated with a DOAC than in those treated with warfarin. Specifically designed prospective studies are warranted to reassess the use of D-dimer as predictor of the risk of recurrent venous thromboembolism in patients treated with DOACs.

Topics: Administration, Oral; Aged; Anticoagulants; Case-Control Studies; Clinical Laboratory Techniques; Clinical Trials as Topic; Female; Fibrin Fibrinogen Degradation Products; Humans; Italy; Male; Middle Aged; Retrospective Studies; Risk; Rivaroxaban; Venous Thromboembolism; Vitamin K; Warfarin

Venous thromboembolism (VTE) is a frequent and morbid complication after injury. Despite utilization of twice-daily enoxaparin, a significant proportion of patients still develop VTE. The purpose of this study was to compare the safety and efficacy of rivaroxaban to enoxaparin for the prevention of VTE in patients with multisystem injuries.. This retrospective cohort analysis evaluated VTE rate in multiply injured patients at a level I trauma Center. Propensity matching was used to compare patients receiving rivaroxaban or enoxaparin. The primary outcome was incidence of VTE during or up to 6 mo after admission. Secondary outcomes included major and minor bleeding, hospital mortality, and hospital length of stay.. A total of 2106 patients were randomly selected from the entire cohort for inclusion. Patients who developed a VTE with no significant difference between groups (14 [1.3%] in the rivaroxaban group and 14 [1.3%] in the enoxaparin group, P = 1) was 1.3%. In addition, there was no difference in deep venous thrombosis (10 [0.9%] in the rivaroxaban group and 12 [1.1%] in the enoxaparin group) or pulmonary embolism (6 [0.6%] in the rivaroxaban group and 2 [0.2%] in the enoxaparin group). Incidence of bleeding, minor or major, was equivalent between groups (P > 0.05). Hospital length of stay and mortality were significantly higher in the enoxaparin group compared with rivaroxaban (11 [1.0%] versus 0 [0%] respectively, P < 0.001).. Rivaroxaban demonstrated a similar incidence of VTE and bleeding complications as enoxaparin. Rivaroxaban may be a safe and effective alternative for VTE prophylaxis in this high-risk population.

Topics: Adult; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Length of Stay; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Wounds and Injuries

The purpose of this study was to evaluate the efficacy and safety of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE).We performed a retrospective chart review of cancer patients with a pulmonary embolism, deep vein thrombosis, or both. Our analysis included all patients who received rivaroxaban from March 2013 to June 2016 at the Hemato-Oncology Division at the Pusan National University Hospital in Korea.Preliminary results identified 123 patients with a history of cancer that were treated with rivaroxaban. The average duration of rivaroxaban therapy was 95.25 days. While 35 patients had resolved VTE after the initiation of rivaroxaban, only one patient had it recur on rivaroxaban treatment. Major bleeding was observed in 6 (4.9%) patients and minor bleeding in 12 (9.8%) patients. The majority of bleeding events occurred spontaneously and most incidences of bleeding could be treated conservatively. Recurrence and major bleeding events on rivaroxaban were relatively low despite the fact that many patients had metastatic disease. Among 52 patient deaths (42.3%), none were due to VTE or bleeding complications; the cause of death in the majority of cases was cancer progression.Rivaroxaban is effective and safe for the treatment of cancer-associated VTE.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Republic of Korea; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Young Adult

We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy.

Topics: Aged; Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Long Term Adverse Effects; Male; Middle Aged; Patient Selection; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Background There is increasing evidence indicating oral factor Xa inhibitors can be used for secondary prevention of venous thromboembolism. Studies are needed to compare oral factor Xa inhibitors, low molecular weight heparins, and warfarin in the oncology population. The purpose of this study is to evaluate the recurrent venous thromboembolism incidence in oncology patients utilizing oral Xa inhibitors, low molecular weight heparins, or warfarin. Methods Using retrospectively collected data, we compared the recurrent venous thromboembolism incidence in oncology patients taking rivaroxaban/apixaban, enoxaparin, or warfarin with at least three months of follow-up. Patients were included if they had an active cancer, venous thromboembolism, and taking warfarin, enoxaparin, or rivaroxaban/apixaban. The primary endpoint was the first episode of recurrent venous thromboembolism at three months. Secondary endpoints included recurrent venous thromboembolism after six months, major bleeding, and mortality. Results Of 127 venous thromboembolism patients, 48 received rivaroxaban or apixaban, 23 received enoxaparin, and 56 received warfarin. The three most common cancer diagnoses were lung (21%), colorectal (14%), and breast (14%). There was no difference in venous thromboembolism recurrence at three months between the rivaroxaban/apixaban (0%), warfarin (3.6%), and the enoxaparin cohorts (4.4%) (p = 0.8319). Major bleeding at three months was only seen in one patient in the enoxaparin arm (4.2%). Mortality at three months was 0%, 3.6%, and 17.4% in the rivaroxaban/apixaban, warfarin, and enoxaparin cohorts, respectively. Conclusion The results of this retrospective study suggest that oral factor Xa inhibitors are potential options for cancer patients with venous thromboembolism. However, randomized, controlled trials are needed to confirm these results.

Topics: Aged; Aged, 80 and over; Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Rivaroxaban; Secondary Prevention; Venous Thromboembolism; Warfarin

Two large randomized controlled trials examined the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE). The aim of this epidemiological study was to analyze a cohort of Italian patients affected by VTE who were treated with rivaroxaban in clinical practice. The data were collected by physicians using an online electronic questionnaire. The study was performed during a 6-month period from January to June 2014. We analyzed the clinical characteristics, risk factors for VTE, comorbidities, diagnostic techniques, and treatments in the whole population and in the subgroups with deep vein thrombosis (DVT) only, pulmonary embolism (PE) only, and DVT+PE. Overall, 75.9% of patients were affected by DVT; 20% of patients had DVT and PE; and 4.8% of patients had only PE. Approximately 90% of patients were symptomatic upon diagnosis, and 46.3% of patients required hospitalization. More than half of the patients switched to rivaroxaban after receiving another anticoagulant therapy. The main reasons for changing treatment included difficulties in managing vitamin K antagonists, patient choice, and prothrombin time-international normalized ratio (PT-INR) instability. The switch to rivaroxaban occurred after a mean of 1.8 PT-INR measurements. Clinical characteristic were overall similar to those of patients enrolled in prior clinical trials evaluating the safety and efficacy of rivaroxaban.

Topics: Adult; Aged; Anticoagulants; Disease Management; Drug Substitution; Humans; International Normalized Ratio; Italy; Middle Aged; Pulmonary Embolism; Risk Factors; Rivaroxaban; Surveys and Questionnaires; Venous Thromboembolism

To evaluate the use of direct-acting oral anticoagulants in patients with cancer and venous thromboembolism (VTE) treated at Ochsner Medical Center with the intent of determining the efficacy and safety of these agents.. Patients were identified by a retrospective data extraction of patients treated at Ochsner Medical Center from January 1, 2013, through December 31, 2015. Patients were included for review if they were ≥18 years of age, with a confirmed diagnosis of VTE and active or history of cancer, and if they received dabigatran, apixaban, rivaroxaban, or edoxaban for at least 6 months. The primary objectives were the rate of recurrence of VTE and the incidence of bleeding at 6 months.. Thirty-seven patients were identified. Twelve patients were diagnosed with PE, 21 with DVT, 3 with DVT and PE, and 1 with DVT and superficial vein thrombosis (SVT). Apixaban was used most often (n = 27). No patients experienced a recurrent DVT or PE at 6 months. Two patients experienced adverse effects during treatment.. In this single-center, retrospective, observational study in patients with cancer receiving DOAC therapy, there were no episodes of recurrent VTE and only 2 episodes of clinically significant bleeding.

Topics: Administration, Oral; Aged; Anticoagulants; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Venous Thromboembolism

In a major centre for orthopaedic surgery, we retrospectively analysed 1,469 patients who underwent elective hip replacement since 2010. All patients but 2 received anticoagulation postoperatively and rivaroxaban was the preferred choice for anticoagulation.. The incidence of all adverse events in those who received rivaroxaban was 1.7%. Only 0.3% had a minor upper gastrointestinal bleed and 1.3% developed a minor wound bleeding or haematoma. The occurrence of symptomatic venous thromboembolism (VTE) was 0.2% of all patients.. In this analysis, the incidence of adverse events was lower than the previously 4 published national figures.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; England; Female; Humans; Incidence; Male; Practice Patterns, Physicians'; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

The objective was to describe the implementation, work flow, and differences in outcomes between a pharmacist-managed clinic for the outpatient treatment of venous thromboembolism (VTE) using a non-vitamin K oral anticoagulant versus care by a primary care provider (PCP).. Patients in the studied health system that are diagnosed with low-risk VTE in the emergency department are often discharged without hospital admission. These patients are treated with a non-vitamin K oral anticoagulant and follow-up either in a pharmacist-managed VTE clinic or with their PCP. Pharmacists in the VTE clinic work independently under a collaborative practice agreement (CPA). An evaluation of 34 patients, 17 in each treatment arm, was conducted to compare the differences in treatment-related outcomes of rivaroxaban when managed by a pharmacist versus a PCP.. The primary endpoint was a 6-month composite of anticoagulation treatment-related complications that included a diagnosis of major bleeding, recurrent thromboembolism, or fatality due to either major bleeding or recurrent thromboembolism. Secondary endpoints included number of hospitalizations, adverse events, and medication adherence. There was no difference in the primary endpoint between groups with one occurrence of the composite endpoint in each treatment arm (p = 1.000), both of which were recurrent thromboembolic events. Medication adherence assessment was formally performed in eight patients in the pharmacist group versus no patients in the control group. No differences were seen among other secondary endpoints.. The pharmacist-managed clinic is a novel expansion of clinical pharmacy services that treats patients with low-risk VTEs with rivaroxaban in the outpatient setting. The evaluation of outcomes provides support that pharmacist-managed care utilizing standardized protocols under a CPA may be as safe as care by a PCP.

Topics: Ambulatory Care Facilities; Anticoagulants; Case-Control Studies; Emergency Service, Hospital; Female; Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Outcome Assessment, Health Care; Pharmacists; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Cancer is a known hypercoagulable state that leads to an increased risk of venous thromboembolism (VTE). Low molecular weight heparin remains the preferred anticoagulant for VTE in patients with cancer over vitamin K antagonist. However, the preferred anticoagulant in prevention of stroke and systemic embolism in atrial fibrillation (AF) in patients with cancer has yet to be determined. The direct oral anticoagulants (DOACs) are increasingly being utilized; however their role in cancer has only recently been investigated. The objective of this retrospective cohort was to describe real-world anticoagulation prescribing patterns in cancer patients at a large academic medical center between January 1, 2013 and October 31, 2016. We sought to assess the safety, tolerability, and efficacy of DOACs in patients with cancer for either VTE and/or AF. Patient demographic, clinical characteristics, as well as bleeding and thrombotic events were collected. There were 214 patients in our analysis, of which 71 patients (33%) received a DOAC [apixaban (n = 22), dabigatran (n = 17), and rivaroxaban (n = 32)]. There were fewer bleeding events and/or discontinuations in the DOAC group compared to enoxaparin (13 vs. 27, p = 0.022). There was no difference in major or minor bleeds or thromboembolic events in comparing DOAC to enoxaparin or DOAC to warfarin. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs compared to warfarin or enoxaparin in patients with cancer. DOACs may represent an alternative to warfarin or enoxaparin in patients with cancer for VTE and/or stroke reduction in AF.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Enoxaparin; Hemorrhage; Humans; Middle Aged; Neoplasms; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Thrombosis; Treatment Outcome; Venous Thromboembolism; Warfarin

The objective of this project was to compare the time from initiation of oral anticoagulation to hospital discharge between warfarin and direct oral anticoagulants (DOACs) for the treatment of acute venous thromboembolism (VTE). This retrospective observational study was done at a single VA medical center. A total of 107 patients were included, with 42 patients (39%) in the DOAC group, which included rivaroxaban, dabigatran, and apixaban, and 65 patients (61%) in the warfarin group. Variables collected through chart review included comorbid conditions, time from initiation of oral anticoagulation to discharge, emergency department (ED) visits and readmission within 30 or 90 days, and bleeding events. The DOAC group had a shorter time to discharge compared to the warfarin group (28 vs. 114 h, p < 0.001). There were similar 30 and 90-day hospital readmission rates and/or ED visits for DOACs (23.8 and 33.3%) compared to warfarin (18.5 and 30.8%), including those related to bleeding of any severity (11.9% for DOACs vs. 9.2% for warfarin; p = 0.75). There was one major bleeding event in the DOAC group and two in the warfarin group. The use of DOACs for the treatment of acute VTE in hospitalized patients was associated with shorter time to hospital discharge when compared to warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Dabigatran; Female; Hemorrhage; Humans; Length of Stay; Male; Middle Aged; Patient Readmission; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

To assess the outcome of direct oral anticoagulants (DOACs), specifically Xa inhibitors: rivaroxaban and apixaban, for the treatment of venous thromboembolism (VTE) of atypical location (VTE-AL), portal, mesenteric, hepatic, splenic, gonadal, renal, and cerebral veins, prospectively collected data of Mayo Thrombophilia Clinic Registry were used.. Patients with acute VTE-AL treated with DOACs, enrolled between March 1, 2013, and February 1, 2017, were compared with patients with VTE of typical location (VTE-TL: deep vein thrombosis of extremities and/or pulmonary embolism) receiving DOACs and with patients with VTE-AL treated with enoxaparin.. Out of 623 patients with acute VTE receiving the study drug within 14 days of diagnosis, there were 63 with VTE-AL: 36 on DOAC, 23 on enoxaparin, and 4 on warfarin; 352 received DOAC for VTE-TL. The VTE-AL treated with DOAC/enoxaparin included the following: splanchnic (26/22), ovarian (8/2), renal (3/5), and cerebral veins (1/1), respectively. Recurrence rate (per 100 person-years) for the VTE-AL group receiving DOAC was 7.3, which was not different when compared with those for VTE-TL (2.4; P=.13) and VTE-AL groups receiving enoxaparin (23.7; P=.37). Major bleeding rate in the VTE-AL group receiving DOAC was not different compared with those for VTE-TL (7.2 vs 3.0; P=.26) and VTE-AL groups on enoxaparin (22.4; P=.31). Mortality was higher in the VTE-AL group on DOAC compared with the VTE-TL group (21.45 [95% CI, 7.87-46.69] vs 8.26 [95% CI, 5.35, 12.20]; P=.03). All patients with VTE-AL with events had cancer.. The VTE recurrence and bleeding rates for rivaroxaban and apixaban used in VTE-AL are not different from those in patients with VTE-TL and similar to that for enoxaparin.

Topics: Aged; Anticoagulants; Drug-Related Side Effects and Adverse Reactions; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Purpose Although low-molecular-weight heparin (LMWH) remains the standard of care, factor Xa inhibitors such as rivaroxaban may serve as an alternative treatment for venous thromboembolism (VTE) in patients with active malignancy. The purpose of the analysis was to evaluate outcomes of VTE management in cancer patients treated with rivaroxaban compared to enoxaparin. Methods This single-center retrospective analysis was conducted on patients with malignancy-associated VTE initiated on treatment with either rivaroxaban or enoxaparin. The primary endpoint was the incidence of recurrent VTE. Secondary outcomes included a comparison in rates of bleeding, mean duration of treatment, and mean time to recurrence of VTE. Results A total of 45 patients were included in each group. The incidence of recurrent VTE was 8.9% in the rivaroxaban group versus 13.3% in the enoxaparin group ( p = 0.53). There were no statistically significant differences in the secondary outcomes with the exception of longer mean duration of treatment in the rivaroxaban group compared to the enoxaparin group (169 vs. 110 days, respectively; p = 0.04). Conclusions This study provides important preliminary information regarding the efficacy and safety of rivaroxaban for treatment of VTE in cancer patients. Although LMWH should remain the standard of care, these results provide initial reassurance that rivaroxaban serves as a viable alternative in the event that injectable anticoagulation is not an acceptable approach to VTE management.

Topics: Aged; Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Recurrence; Retrospective Studies; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

Rivaroxaban (RXB) is an orally active direct inhibitor of the activated serine protease Factor Xa, given as monotherapy in the treatment of venous thromboembolism (VTE). It has been characterized in vitro as a substrate for the active, nonsaturable efflux via P-gp transporter, limiting its high permeability. Therefore, the role of P-gp inhibiting polymers in enhancing the biopharmaceutical performance of RXB by preparing polymeric amorphous solid dispersion and subsequent improvement in solubility and permeability was investigated. Initially, solubility parameter and Flory-Huggins interaction parameter were determined for miscibility studies between drug and polymers. Binary dispersions were prepared by dissolving drug with polymers eudragit S100, eudragit L100, and soluplus in common solvent (5% v/v water in tetrahydrofuran) using spray dryer. Prepared binary dispersions were analyzed by differential scanning calorimetry (DSC), microscopy, powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy (FTIR), dynamic vapor sorption (DVS), and solution nuclear magnetic resonance (NMR) spectroscopy. Superior performance of binary dispersions was observed upon dissolution and solubility studies over micronized active pharmaceutical ingredient. Amorphous solid dispersion (ASD) prepared with soluplus showed 10-fold increase in apparent solubility and maintenance of supersaturation for 24 h compared to the crystalline RXB. Further, pharmacokinetic study performed in animals was in good correlation with the solubility data. Increases of 5.7- and 6.7-fold were observed in AUC and C

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Caco-2 Cells; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Drug Compounding; Drug Liberation; Excipients; Factor Xa Inhibitors; Gastrointestinal Absorption; Humans; Male; Models, Animal; Polymers; Powders; Rats; Rats, Wistar; Rivaroxaban; Spectroscopy, Fourier Transform Infrared; Venous Thromboembolism; X-Ray Diffraction

: A high risk of venous thromboembolism (VTE) recurrence requires extended anticoagulation but limits the options to control heavy menstrual bleeding (HMB) in women of reproductive age. We report the management of HMB in a 48-year-old woman with a history of menometrorrhagia, recurrent VTE and multiple VTE risk factors. Due to the occurrence of HMB during extended rivaroxaban treatment, the presence of a uterine fibroid and the contraindication to interrupt anticoagulation for high risk of VTE recurrence, she received hormonal treatment first with a gonadotropin-releasing hormone agonist and then with progestin. This strategy allowed to adequately control HMB, without rivaroxaban discontinuation or dose reduction, and no new thromboembolic and no more bleeding events occurred over a long follow-up period of more than 20 months. In conclusion, the use of hormonal therapy in VTE women requiring long-term anticoagulation may be an option to control HMB, without further increasing the risk of VTE recurrence.

Topics: Anticoagulants; Disease Management; Female; Gonadotropin-Releasing Hormone; Humans; Menorrhagia; Middle Aged; Progestins; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

The incidence of venous thromboembolism (VTE) is lower in Asian populations than in Western populations. The objective of the present study was to evaluate the annual age- and sex-adjusted incidence (ASR) of VTE from 2009 to 2013 in South Korea. In addition, annual change in the pattern of VTE treatment during the study period was estimated because a new direct oral anticoagulant (DOAC) had become available and was covered by health insurance in Korea beginning in January 2013. VTE cases from 2009 to 2013 were retrospectively identified based on both diagnostic and medication codes of anticoagulants used for initial treatment using the Korean Health Insurance Review and Assessment Service (HIRA) databases. The incidence of VTE increased yearly. It was significantly higher in the older population than in the younger population, and it was higher in females than in males. In 2009, ASRs of VTE, deep vein thrombosis, and pulmonary embolism were 21.3, 8.1, and 13.2 cases per 100,000 individuals, respectively in 2009. These increased to 29.2, 12.7, and 16.6 cases per 100,000, respectively, in 2013. Prescription rates of warfarin and low-molecular-weight heparin decreased with the introduction of a new anticoagulant in 2013. The proportion of subjects who underwent mechanical procedures decreased annually. The ASR of VTE in Korea continuously increased from 2009 to 2013, reflecting an increased awareness and detection of VTE as well as improved survival of patients with cancer and other morbidities. Following its introduction, DOAC rapidly replaced other anticoagulants for the treatment of VTE.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Infant; Infant, Newborn; Male; Middle Aged; Pulmonary Embolism; Republic of Korea; Retrospective Studies; Rivaroxaban; Sex Factors; Venous Thromboembolism; Venous Thrombosis; Warfarin; Young Adult

Randomized clinical trials comparing direct oral anticoagulants (DOACs) to warfarin in cancer patients have not been performed. We evaluated the effectiveness and associated risk of DOACs vs warfarin, as well as comparisons of DOACs, in a large population of cancer patients with nonvalvular atrial fibrillation (AF). Using the MarketScan databases, we identified 16 096 AF patients (mean age, 74 years) initiating oral anticoagulant and being actively treated for cancer between 2010 and 2014. Anticoagulant users were matched by age, sex, enrollment date, and drug initiation date. Study end points were identified with diagnostic codes and included ischemic stroke, severe bleeding, other bleeding, and venous thromboembolism (VTE). Cox regression was used to estimate associations of anticoagulants with study end points. Compared with warfarin, rates of bleeding (hazard ratio [95% confidence interval]) were similar in rivaroxaban (1.09 [0.79, 1.39]) and dabigatran (0.96 [0.72, 1.27]) users, whereas apixaban users experienced lower rates (0.37 [0.17, 0.79]). Rates of ischemic stroke did not differ among anticoagulant users. Compared with warfarin, rate of VTE (hazard ratio [95% confidence interval]) was lower among rivaroxaban (0.51 [0.41, 0.63]), dabigatran (0.28 [0.21, 0.38]), and apixaban (0.14 [0.07, 0.32]) users. In head-to-head comparisons among DOACs, dabigatran users had lower rates of VTE than rivaroxaban users; apixaban users had lower rates of VTE and severe bleeding than rivaroxaban users. In this population of patients with AF and cancer, DOAC users experienced lower or similar rates of bleeding and stroke compared with warfarin users, and a lower rate of incident VTE.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Databases, Factual; Hemorrhage; Humans; Middle Aged; Neoplasms; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Venous Thromboembolism; Warfarin; Young Adult

: Due to their ease of use, the direct oral anticoagulants (DOACs) are an attractive treatment option for cancer-associated venous thromboembolism (VTE) and have been readily adopted by many clinicians. A recent published study comparing a DOAC (edoxaban) to the current standard-of-care low molecular weight heparin dalteparin for the treatment of cancer-associated thrombosis showed that edoxaban was noninferior to dalteparin for recurrent VTE, but the risk of major bleeding was higher. We present three patients with high-risk gastrointestinal malignancies complicated by cancer-associated VTE with progression of thrombosis while treated with the oral direct Xa inhibitor rivaroxaban. Upon switching therapy to low molecular weight heparin, we found that these patients had clinical and radiologic improvement of VTE. More studies are needed to evaluate the efficacy of rivaroxaban in high-risk gastrointestinal-VTE. We suggest that in some patients, DOACs may not be sufficient for the treatment of VTEs related to high-risk gastrointestinal malignancies.

Topics: Aged; Factor Xa Inhibitors; Female; Gastrointestinal Neoplasms; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism

Anticoagulation is used to treat venous thromboembolism (VTE) in cancer patients, but may be associated with an increased risk of bleeding. VTE recurrence and major bleeding were assessed in cancer patients treated for VTE with the most currently prescribed anticoagulants in clinical practice. Newly diagnosed cancer patients (first VTE 1/1/2013-05/31/2015) who initiated rivaroxaban, low-molecular-weight heparin (LMWH), or warfarin were identified from Humana claims data and observed until end of eligibility or end of data availability. VTE recurrence was a hospitalization with a primary diagnosis of VTE ≥7 days after first VTE. Major bleeding events on treatment were identified using validated criteria. Cohorts were compared using Kaplan-Meier rates at 6 and 12 months and Cox proportional hazards models. Cohorts were adjusted for their differences at baseline. A total of 2428 patients (rivaroxaban: 707; LMWH: 660; warfarin: 1061) met inclusion criteria. Patient characteristics were well balanced after weighting. There was a trend for lower VTE recurrence rates in rivaroxaban users compared to LMWH users at 6 months (13.2% vs. 17.1%; P = .060) and significantly lower at 12 months (16.5% vs. 22.2%; P = .030) [HR: 0.72, 95% CI: (0.52-0.95); P = .024]. VTE recurrence rates were also lower for rivaroxaban than warfarin users at 6 months (13.2% vs. 17.5%; P = .014) and 12 months (15.7% vs. 19.9%; P = .017) [HR: 0.74, 95% CI: (0.56-0.96); P = .028]. Major bleeding rates were similar across cohorts. This real-world analysis suggests cancer patients with VTE treated with rivaroxaban had significantly lower risk of recurrent VTE and similar risk of bleeding compared to those treated with LMWH or warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

Screening for primary hypercoagulable states (PHSs) in venous thromboembolism (VTE) patients was not mandated in the EINSTEIN trials; and therefore, few patients with a known PHS were available for analysis. We sought to assess the effectiveness and safety of rivaroxaban versus warfarin for treatment of VTE in patients with a known PHS.. Using MarketScan claims data from 1/2012-9/2015, we identified adults with a primary diagnosis of VTE during a hospitalization/emergency department visit (the index event), with ≥180-days of continuous insurance coverage prior to the index event, a documented diagnosis for a PHS and newly-initiated as an outpatient on rivaroxaban or warfarin within 30-days of the index VTE. Rivaroxaban and warfarin users were 1:1 propensity-score matched. Balance between cohorts was evaluated by inspecting standardized differences for baseline covariates (<0.1 considered well-balanced). Patients were followed up to 12-months from the index event or until occurrence of an endpoint, switch/discontinuation of index oral anticoagulation or insurance disenrollment. Rates of recurrent VTE and major bleeding were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs).. We matched 403 rivaroxaban and 403 warfarin patients with VTE and a known PHS. All baseline covariates had a standardized difference < 0.1. Rivaroxaban use was associated with a non-significant reduction in recurrent VTE (HR = 0.70, 95%CI = 0.33-1.49) and major bleeding (HR = 0.55, 95%CI = 0.16-1.86) versus warfarin.. In routine practice, the effectiveness and safety of rivaroxaban versus warfarin in VTE patients with a known PHS appears to be similar to that observed in the EINSTEIN trial program.

Topics: Anticoagulants; Blood Coagulation Disorders; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Outpatients; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Topics: Emergency Service, Hospital; Factor Xa Inhibitors; Humans; Length of Stay; Male; Middle Aged; Patient Readmission; Rivaroxaban; Venous Thromboembolism

The objective of this study is to evaluate the effectiveness of different rivaroxaban dosage regimens in preventing ischemic stroke and systemic thromboembolism among Asians. A retrospective cohort study was conducted on data from nationwide insurance claims in Taiwan. Patients with non-valvular atrial fibrillation under warfarin or rivaroxaban therapy were included. Propensity score matching was used to balance the covariates, and Cox-proportional hazard models were applied to compare the effectiveness and safety of each treatment group. Rivaroxaban was associated with a significantly lower risk of venous thromboembolism (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.29-0.92, P = 0.02) and intracranial hemorrhage (HR: 0.48; 95% CI: 0.32-0.72, P < 0.001) than warfarin. Rivaroxaban 20 mg and 15 mg were associated with a significantly lower risk of ischemic stroke (20 mg, HR: 0.48; CI: 0.29-0.80, P = 0.005; 15 mg, HR: 0.69; CI: 0.53-0.90, P = 0.005), but rivaroxaban 10 mg was not. In the subgroup analysis of patients older than 65 years, the results were generally the same, except that rivaroxaban had a significantly lower risk of ischemic stroke than warfarin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Intracranial Hemorrhages; Male; Retrospective Studies; Rivaroxaban; Stroke; Taiwan; Treatment Outcome; Venous Thromboembolism; Warfarin

The effectiveness of rivaroxaban to reduce post-thrombotic syndrome in patients with venous thromboembolism is largely unknown. We compared rates of post-thrombotic syndrome in patients given rivaroxaban versus warfarin in a cohort of patients with incident venous thromboembolism receiving routine clinical care.. We linked Danish nationwide registries to identify all patients with incident venous thromboembolism who were new users of rivaroxaban or warfarin and compared rates of post-thrombotic syndrome using an inverse probability of treatment-weighting approach to account for baseline confounding.. We identified 19,957 oral anticoagulation-naive patients with incident venous thromboembolism treated with warfarin or rivaroxaban (mean age, 64 years; 48% were female, 45.5% had pulmonary embolism). The propensity-weighted rate of post-thrombotic syndrome at 3 years follow-up was 0.53 incidents per 100 person-years with rivaroxaban versus 0.55 per 100 person-years with warfarin, yielding a hazard rate of 0.88 (95% confidence interval, 0.66-1.17). This association remained consistent across types of venous thromboembolism (deep venous thrombosis vs pulmonary embolism, and provoked vs unprovoked venous thromboembolism) and when censoring patients with recurrent venous thromboembolism.. In this clinical practice setting, rivaroxaban was associated with lower but statistically nonsignificant rates of post-thrombotic syndrome, which did not appear to be mediated only by an effect on recurrent venous thromboembolism.

Topics: Anticoagulants; Denmark; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postthrombotic Syndrome; Registries; Risk Factors; Rivaroxaban; Time Factors; Venous Thromboembolism; Warfarin

The effectiveness and safety of acute venous thromboembolism (VTE) treatment with rivaroxaban, demonstrated in phase-III trials, needs to be confirmed in daily care. To confirm the positive results of phase-III VTE treatment trials with rivaroxaban in daily care, we used data from the ongoing, prospective, non-interventional Dresden NOAC Registry. For this analysis, only patients with acute VTE who started rivaroxaban within 14days after diagnosis of VTE and who were enrolled within these 14days were evaluated with regard to patient characteristics, treatment persistence and clinical outcomes. Between December 1st 2011 and 30th September 2016, 418 patients with acute VTE and rivaroxaban treatment were enrolled. During rivaroxaban treatment (median rivaroxaban exposure 206d; median follow-up 862d) rates of recurrent VTE and ISTH major bleeding were 1.9% and 3.8%, respectively. At 6months. 58.3% of patients were still taking rivaroxaban, 28.2% had a scheduled end of treatment, 7.2% were switched to other anticoagulants, 1.7% had withdrawn their consent and the remaining 3.6% of patients had unplanned complete discontinuation of anticoagulation. After permanent discontinuation of rivaroxaban, 20 patients experienced a recurrent VTE (7 pulmonary embolism±deep vein thrombosis, 13 deep vein thrombosis) with a mean time between last intake of rivaroxaban and VTE recurrence of 374.3±247.6days (range 28-927d). In daily care patients with acute VTE, rivaroxaban demonstrated high effectiveness with acceptable major bleeding rates. Initial dosing was according to label in over 90% of patients and persistence to rivaroxaban therapy was adequate with low rates of unplanned complete discontinuation.

Topics: Adult; Aged; Cohort Studies; Drug Administration Schedule; Factor Xa Inhibitors; Female; Follow-Up Studies; Germany; Humans; Male; Middle Aged; Patient Care; Prospective Studies; Registries; Rivaroxaban; Venous Thromboembolism

Surgical site infection (SSI) is a debilitating complication of lower limb arthroplasty with significant morbidity and increased costs. Numerous risk factors are associated with SSI.. In an effort to identify novel risk factors for SSI, we undertook a retrospective cohort study of 1832 primary total hip arthroplasties and 2100 primary total knee arthroplasties performed in our high volume arthroplasty unit over a 2-year period.. Two risk factors were identified for SSI following total hip arthroplasty: body mass index ≥30 and peri-operative blood transfusion. Eight risk factors were identified for SSI following total knee arthroplasty: hypertension, peri-operative blood transfusion, skin closure using 2-octyl cyanoacrylate, use of oral steroids, reduced serum mean cell volume, reduced mean cell hemoglobin, elevated serum neutrophil count, and use of warfarin or rivaroxaban for venous thromboembolism prophylaxis.. Our work proposes a number of previously undocumented risk factors in relation to SSI. Further investigation is required to ascertain the magnitude of their effect.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Transfusion; Body Mass Index; Cyanoacrylates; Female; Humans; Male; Middle Aged; Neutrophils; Retrospective Studies; Risk Factors; Rivaroxaban; Steroids; Surgical Wound Infection; Venous Thromboembolism; Warfarin; Young Adult

Postthrombotic syndrome (PTS) is a frequent complication of venous thromboembolism (VTE). Using MarketScan claims data from January 2012 to June 2015, we identified adults with a primary diagnosis code for VTE during a hospitalization/emergency department visit, ≥6 months of insurance coverage prior to the index event and newly started on rivaroxaban or warfarin within 30 days of the index VTE. Patients with <4-month follow-up postindex event or a claim for any anticoagulant during 6-month baseline period were excluded. Differences in baseline characteristics between rivaroxaban and warfarin users were adjusted for using inverse probability of treatment weights based on propensity scores. Patients were followed for the development of PTS starting 3 months after the index VTE. Cox regression was performed and reported as hazard ratios with 95% confidence intervals (CIs). In total, 10 463 rivaroxaban and 26 494 warfarin users were followed for a mean of 16 ± 9 (range, 4-39) months. Duration of anticoagulation was similar between cohorts (median = 6 months). Rivaroxaban was associated with a 23% (95% CI: 16-30) reduced hazard of PTS versus warfarin. Rivaroxaban was associated with a significant risk reduction in symptoms of PTS compared to warfarin in patients with VTE treated in routine practice.

Topics: Adult; Female; Humans; Male; Postthrombotic Syndrome; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Frailty predicts poorer outcomes in patients receiving anticoagulation. We assessed the effectiveness and safety of rivaroxaban vs warfarin in frail patients experiencing venous thromboembolism.. Using US MarketScan claims data from January 2012-December 2016, we identified frail patients (using the Johns Hopkins Claims-Based Frailty Indicator score) who had ≥1 primary hospitalization/emergency department visit diagnosis codes for venous thromboembolism, received rivaroxaban or warfarin as their first outpatient oral anticoagulant within 30 days of the index event, and had ≥12 months of insurance prior to the index venous thromboembolism. Differences in baseline covariates between cohorts were adjusted using inverse probability of treatment weights based on propensity scores. The primary endpoint was the composite of recurrent venous thromboembolism or major bleeding. Patient claims were tracked for up to 12 months after the index venous thromboembolism or until endpoint occurrence oral anticoagulant discontinuation/switch, insurance disenrollment, or end of follow-up. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).. Of 58,089 incident venous thromboembolism patients identified, 6869 (1365 rivaroxaban and 5504 warfarin users) were classified as frail. Rivaroxaban reduced patients' hazard of the composite of recurrent venous thromboembolism or major bleeding (HR 0.75; 95% CI, 0.57-0.98) and recurrent venous thromboembolism alone (HR 0.65; 95% CI, 0.44-0.97) compared with warfarin. No significant difference in major bleeding was observed between cohorts (HR 0.88; 95% CI, 0.61-1.27).. Frail patients experiencing a venous thromboembolism and given rivaroxaban experience less recurrent venous thromboembolism, with at least as good bleeding outcomes, as patients prescribed warfarin.

Topics: Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Frail Elderly; Humans; Male; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

A 19-year-old man was referred due to sudden onset of right foot pain and chest discomfort. Contrast-enhanced computed tomography revealed massive thrombi in the right pulmonary artery and femoral vein. The patient's father had experienced multiple recurrences of venous thromboembolism (VTE) and was diagnosed with inherited antithrombin deficiency by a genetic examination. The patient was administered the oral factor Xa inhibitor rivaroxaban (30 mg). After seven days, the thrombus disappeared. Rivaroxaban (15 mg) was continued for 6 months with no recurrence, indicating the efficacy of this factor Xa inhibitor for the treatment and prevention of VTE in patients with antithrombin deficiency.

Topics: Antithrombin III Deficiency; Factor Xa Inhibitors; Humans; Male; Recurrence; Rivaroxaban; Venous Thromboembolism; Young Adult

This study was conducted to describe the real-world hospital length of stay in patients treated with all of the U.S. Food and Drug Administration approved direct oral anticoagulants (DOACs) versus warfarin for new-onset venous thromboembolism (VTE) at a large, tertiary, academic medical center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 441 patients included, 261 (57%) patients received DOACs versus 180 (41%) patients received warfarin. In the DOAC group, a total of 92 (35%) patients received rivaroxaban, followed by 83 (32%) patients received apixaban, 50 (19%) patients received dabigatran, and 36 (14%) patients received edoxaban. Patients initiated on DOACs had a statistically significant shorter hospital length of stay compared to patients initiated on warfarin (median 3 days, [IQR 0-5] vs. 8 days [IQR 5-11], P < 0.05). Despite the shorter hospital length of stay in patients receiving DOACs, the overall reported differences between the DOACs group and the warfarin group in terms of recurrent VTE, major bleeding, intracranial bleeding, and gastrointestinal bleeding at 3 and 6 months were deemed to be statistically insignificant.

Topics: Adult; Aged; Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Length of Stay; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

Essentials Net benefit of venous thromboprophylaxis (VTE) in patients hospitalized for infections is unknown. MAGELLAN trial subgroup analysis was performed for patients hospitalized for acute infectious diseases. At day 35, prolonged rivaroxaban prophylaxis reduced VTE compared to enoxaparin (4.2% vs. 6.6%). Rivaroxaban prophylaxis reduced VTE in patients hospitalized for active lung infections.. Background Despite the well-established association between infection and venous thromboembolism (VTE), there are few data specifically assessing the efficacy and safety of the VTE prophylaxis strategies for patients hospitalized for acute infectious diseases. Objectives To estimate the incidence of VTE and bleeding outcomes, comparing prolonged prophylaxis with rivaroxaban 10 mg daily for 35 days with enoxaparin 40 mg daily for 10 days. Patients/Methods A subgroup analysis of patients hospitalized for acute infectious diseases in the MAGELLAN trial was performed. The primary efficacy outcome was the composite of asymptomatic proximal or symptomatic VTE at days 10 and 35. The principal safety outcome was the composite of major or clinically relevant non-major bleeding. Results Three thousand one hundred and seventy-three patients with acute infectious diseases leading to hospitalization were randomized to either rivaroxaban (n = 1585) or enoxaparin/placebo (n = 1588), and received at least one dose of study medication. At day 10, primary composite efficacy outcomes did not differ between prophylaxis strategies (rivaroxaban, 2.7%; and enoxaparin, 3.7%). At day 35, there were fewer VTE events with rivaroxaban (4.2%) than with enoxaparin (6.6%) (relative risk [RR] 0.64; 95% confidence interval [CI] 0.45-0.92). Patients with pulmonary infections randomized to rivaroxaban had a lower incidence of VTE both at 10 days (RR 0.50, 95% CI 0.28-0.90) and at 35 days (RR 0.54, 95% CI 0.33-0.87). Primary safety outcome events were increased with rivaroxaban (RR 2.42, 95% CI 1.60-3.66). Conclusions Prolonged rivaroxaban prophylaxis reduced the incidence of VTE in patients hospitalized for acute infectious diseases, particularly those involving the lungs. Efficacy benefits were, in part, offset by bleeding outcomes. ClinicalTrials.gov Number: NCT 00571649.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Drug Administration Schedule; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Patient Admission; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

A paucity of real-world data evaluating rivaroxaban in provoked venous thromboembolism (VTE) exists. We assessed the effectiveness and safety of rivaroxaban versus warfarin in provoked VTE patients treated in routine practice. Using MarketScan claims data from 1/2012 to 12/2016, we identified adults who had ≥ 1 primary hospitalization/emergency department discharge diagnosis code for VTE (index event) and a provoking factor, received rivaroxaban or warfarin as their first outpatient oral anticoagulant within 30-days of the index event and had ≥ 12-month of insurance coverage prior the index VTE. Provoking factors included cancer, hospital admission for ≥ 3-consecutive days over the prior 3-months, major surgery, trauma or fracture within 90-days or pregnancy within 42-weeks of the index VTE. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity-scores (residual standardized differences < 0.1 achieved for all covariates after adjustment). The incidence of the composite endpoint of recurrent VTE or major bleeding at 3- and 6-months was compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). We included 4454 rivaroxaban and 13,164 warfarin users with provoked VTE. At 3- and 6-months, rivaroxaban was associated with a reduced hazard of the composite endpoint (HR 0.72, 95% CI 0.61-0.84 and HR 0.69, 95% CI 0.60-0.80) and recurrent VTE (HR 0.70, 95% CI 0.59-0.84 and HR 0.71, 95% CI 0.60-0.84) versus warfarin. Major bleeding was non-significantly reduced at 3-months (HR 0.77, 95% CI 0.57-1.06) and significantly reduced at 6-months (HR 0.68, 95% CI 0.53-0.88) with rivaroxaban. Rivaroxaban reduces recurrent VTE and major bleeding risk versus warfarin in provoked VTE patients treated in routine practice.

Topics: Adult; Aged; Anticoagulants; Female; Hemorrhage; Hospitalization; Humans; Insurance, Health; Male; Middle Aged; Recurrence; Rivaroxaban; Secondary Prevention; Treatment Outcome; Venous Thromboembolism; Warfarin

In phase III trials, rivaroxaban demonstrated non-inferiority over enoxaparin/warfarin to prevent recurrent venous thromboembolism (VTE), with a reduction of major bleeding. However, compared to provoked VTE, the risk-benefit ratio of rivaroxaban may be different for patients with unprovoked VTE.. In a retrospective claims data analysis using US MarketScan claims from 1/2012 to 12/2016, we included adults with a primary diagnosis of VTE newly-initiated on rivaroxaban or warfarin within 30-days of the incident VTE and with ≥12-months of continuous insurance benefits prior to the VTE (baseline). Patients with provoked VTE, a claim for anticoagulation during baseline or who redeemed prescriptions for ≥1 oral anticoagulant were excluded. Our primary outcomes were recurrent VTE and major bleeding at 6-months using an intention-to-treat (ITT) analysis. Three-month ITT and 12-month on-treatment (30-day permissible gap) analyses were also performed. Inverse probability-of-treatment weights based on propensity-scores and Cox regression were used to compare outcomes.. We identified 10,489 rivaroxaban users and 26,364 warfarin users with incident unprovoked VTE. At 6-months, rivaroxaban was associated with a hazard ratio (HR) of 0.60 (95% confidence interval [CI] = 0.54-0.67) for recurrent VTE (number-needed-to-treat: 59; 95%CI 49-76) and a HR = 0.80 (95% CI = 0.66-0.98) for major bleeding versus warfarin. Our findings remained consistent in the 3- and 12-month analyses.. Consistent with the results from the EINSTEIN phase-III trials, findings of our routine practice study suggest that, in patients with unprovoked VTE, rivaroxaban has the potential to reduce both the risk of major bleeding and recurrent VTE compared to warfarin.

Topics: Aged; Cohort Studies; Female; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism; Warfarin

To investigate the risk of all-cause mortality, recurrent venous thromboembolism (VTE), and hospitalized bleeding in patients with VTE treated with either rivaroxaban or apixaban.. Using Danish nationwide registries, patients with VTE treated with rivaroxaban or apixaban in the period from 1 January 2015 to 30 June 2017 were identified. Standardized absolute risks were estimated based on outcome-specific Cox regression models, adjusted for potential confounders. A total of 8187 patients were included in the study, of which 1504 (18%) were treated with apixaban [50% males, median age 70 years; interquartile range (IQR) 56-80] and 6683 (82%) were treated with rivaroxaban (55% males, median age 67 years; IQR 53-76). The 180 days risk of all-cause mortality was 5.08% [95% confidence interval (95% CI) 4.08% to 6.08%)] in the apixaban group and 4.60% (95% CI 4.13% to 5.18%) in the rivaroxaban group [absolute risk difference: -0.48% (95% CI -1.49% to 0.72%)]. The 180 days risk of recurrent VTE was 2.16% (95% CI 1.49% to 2.88%) in the apixaban group and 2.22% (95% CI 1.89% to 2.52%) in the rivaroxaban group [absolute risk difference of 0.06% (95% CI -0.72% to 0.79%)]. The 180 days risk of hospitalized bleeding was 1.73% (95% CI 1.22% to 2.35%) for patients in the apixaban group and 1.89% (95% CI 1.56% to 2.20%) in the rivaroxaban group [absolute risk difference: 0.16% (95% CI -0.59% to 0.81%)].. In a nationwide cohort of 8187 patients with VTE treated with rivaroxaban or apixaban, there were no significant differences in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding.

Topics: Aged; Aged, 80 and over; Denmark; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Registries; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

There are numerous studies discussing thromboprophylaxis after total joint arthroplasty (TJA), with varying conclusions. Patient inclusion criteria may be different for each study, which may lead to selection bias and misrepresentation of data. This study aimed to investigate if industry funding impacted patient demographics and overall reported outcomes of studies analyzing venous thromboembolism (VTE) prevention after TJA.. Electronic searches were completed using Ovid, PubMed, and Embase databases. Studies were included if (1) they are published in the English language between 2000 and 2016; (2) they included patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA); and (3) they evaluated prevention and control of postoperative VTE with at least one of the following thromboprophylactic agents: aspirin, enoxaparin, dalteparin, dabigatran, apixaban, rivaroxaban, dabigatran, ximelagatran, fondaparinux, or coumadin. Data were extracted and analyzed via mixed-effect logistic regression.. Fifty-seven studies were included; 29 were industry funded, and 28, nonfunded. There were no significant differences between patient's age, body mass index, or revision exclusions between funded and nonfunded studies. Funded studies reported less pulmonary embolisms, fewer events of major bleeding, and significantly less 90-day mortality compared with nonfunded studies.. Industry-funded studies reported less pulmonary embolisms, major bleeding, and mortality compared with nonfunded studies. Detailed demographic data were missing from the literature, and we were unable to demonstrate the cause of different reported outcomes between industry-funded and nonfunded studies. Further investigations should be aimed toward understanding how funded studies report less adverse outcomes in analyzing VTE after TJA.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Conflict of Interest; Dabigatran; Enoxaparin; Female; Fondaparinux; Health Care Sector; Hemorrhage; Humans; Male; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Warfarin

Topics: Administration, Oral; Anticoagulants; Antithrombins; Dabigatran; Dalteparin; Factor Xa Inhibitors; Hemorrhage; Humans; Multicenter Studies as Topic; Neoplasms; Observational Studies as Topic; Patient Acceptance of Health Care; Prospective Studies; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Full- or lower-dose anticoagulant therapy or aspirin can be used for extended therapy in patients with venous thromboembolism (VTE), but information on their relative benefit-risk profiles is limited.. Data from the EINSTEIN-CHOICE trial were used to compare the benefit-risk profiles of extended treatment with rivaroxaban (20 or 10 mg once daily) and aspirin (100 mg once daily) in VTE patients who had completed 6 to 12 months of anticoagulation therapy. One-year cumulative incidences of recurrent VTE and major bleeding were estimated and benefits and risks were calculated by determining the between group differences in a hypothetical population of 10,000 VTE patients treated for 1 year.. A total of 1107 patients were treated with 20 mg of rivaroxaban, 1127 with 10 mg of rivaroxaban, and 1131 with aspirin. The cumulative incidences of recurrent VTE in the rivaroxaban 20-mg, rivaroxaban 10-mg and aspirin groups were 1.9%, 1.6%, and 5.0%, respectively, whereas the cumulative incidences of major bleeding were 0.7%, 0.4% and 0.5%, respectively. The incidences of the combined outcome of recurrent VTE and major bleeding were 2.8% and 3.4% lower in the rivaroxaban 20-mg and 10-mg groups than in the aspirin group. For 10,000 patients treated for 1 year, there would be 284 (95% confidence interval [CI] 106 to 462) and 339 (95% CI 165 to 512) fewer events with rivaroxaban 20 mg or 10 mg than with aspirin.. Compared with aspirin, extended anticoagulation with once daily rivaroxaban reduces recurrent VTE with a favourable benefit-risk profile.. Bayer AG.

Topics: Aspirin; Factor Xa Inhibitors; Female; Humans; Male; Platelet Aggregation Inhibitors; Risk Factors; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Embolism; Humans; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism

Oral anticoagulants used for the primary treatment of venous thromboembolism (VTE) include warfarin and the more recently introduced direct oral anticoagulants (DOACs), including rivaroxaban, apixaban, dabigatran and edoxaban. Information on the comparative safety of these medications in routine clinical practice is lacking. We identified patients with diagnoses for VTE and prescriptions for oral anticoagulants using claims data from a large U.S. insurance database from 2012 to 2017. Marginal structural logistic models were used to examine associations between type of oral anticoagulant and risk of all-cause mortality. Of 62,431 enrolees in this analysis, 51% were female and the mean age was 61.9 years. Initial oral anticoagulant prescriptions were for warfarin (

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Dabigatran; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Risk; Rivaroxaban; Survival Analysis; Thiazoles; Venous Thromboembolism; Warfarin

For treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), rivaroxaban is given in fixed doses without routine coagulation monitoring.. To determine whether monitoring would enhance its benefit-risk profile, we examined whether peak and trough prothrombin time (PT) values measured in 3797 rivaroxaban-treated patients included in the EINSTEIN DVT and PE studies correlated with subsequent recurrent VTE and major bleeding. In addition, we examined the stability of PT values over time and the impact of clinical variables on PT values.. The mean peak PT values at months 3 and 6 or 12 were 21.9 ± 5 and 21.7 ± 6.0 s, respectively, while the mean trough PT values at months 2 and 6 were 15.1 ± 5.1 and 15.3 ± 2.9 s, respectively. Although peak and through PT values were higher in females, and with older age, frailty, active cancer, low body weight, impaired renal function and use of moderate to strong inhibitors of CYP3A4 and/or P-glycoprotein, and were lower in patients taking strong CYP 3A4 inducers, the differences were small and results were overlapping. Neither peak nor trough PT values correlated with recurrent VTE or major bleeding.. PT monitoring is unlikely to improve the benefit-risk profile of rivaroxaban in patients with DVT or PE. The study was registered at www.clinicaltrials.gov as #NCT00440193 (EINSTEIN-DVT) and #NCT00439777 (EINSTEIN-PE).

Topics: Adolescent; Adult; Aged; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism; Young Adult

Direct oral anticoagulants (DOACs) have become an attractive option for the treatment of venous thromboembolism (VTE) in cancer patients. However, their use is currently not recommended as first-line treatment by national guidelines due to limited data in this patient population. The objective of this study was to evaluate the practice and safety patterns of DOACs when used for VTE treatment in the oncology population. This study was a retrospective chart review of adult cancer patients treated at Hackensack University Medical Center from January 2013 to October 2015 who received dabigatran, rivaroxaban, or apixaban for VTE treatment. Of 126 patients screened, 39 patients were included. Thirty-five patients received rivaroxaban and four patients received apixaban. Ten of 39 patients (26%) were not receiving a DOAC dosage consistent with the package insert. No patients experienced clinically significant bleeding, while four patients experienced a minor bleed. Four of 14 thrombocytopenic patients (29%) did not have their DOAC dose held for thrombocytopenia. All patients had their DOACs appropriately held for procedures. Increased education on dosing DOACs according to the package insert is warranted for oncology prescribers. Despite the increased risk for bleeding in cancer patients, no clinically significant bleeding events were identified in our patient cohort. This data suggests that the use of DOACs may be safe to use for VTE treatment in cancer patients and may provide foundation for larger, randomized controlled trials to determine whether DOACs should be used for VTE treatment in cancer patients.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Hemorrhage; Humans; Middle Aged; Neoplasms; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Factor Xa Inhibitors; Hospitalization; Humans; Rivaroxaban; Venous Thromboembolism

Using data from the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN-CHOICE) trial, this study assessed cost impact of continued anticoagulation therapy with rivaroxaban vs aspirin.. Total health-care costs (2016 USD) associated with rivaroxaban and aspirin were calculated as the sum of clinical event costs and drug costs from a US managed care perspective. Clinical event costs were calculated by multiplying event rate by cost of care. One-year Kaplan-Meier clinical event rates for recurrent pulmonary embolism, recurrent DVT, all-cause mortality, and bleeding were obtained from EINSTEIN-CHOICE. Cost of care was determined by literature review. Drug costs were the product of drug price (wholesale acquisition cost) and treatment duration. A one-way sensitivity analysis was conducted.. Rivaroxaban users had lower per patient per month (PPPM) clinical event costs compared with aspirin users ($123, $243, and $381 for rivaroxaban 10 mg, rivaroxaban 20 mg, and aspirin, respectively). However, vs aspirin, PPPM total health-care costs were $24 higher for patients treated with rivaroxaban 10 mg ($143 higher for rivaroxaban 20 mg) due to higher cost of rivaroxaban. With a 15% discount for rivaroxaban 10 mg, the lower cost of clinical events for the rivaroxaban-treated patients more than fully offset the higher drug costs, and yielded a $19 lower total health-care cost.. Continued therapy with rivaroxaban 10 and 20 mg vs aspirin was associated with lower clinical event costs but higher total health-care costs; with a 15% drug discount rivaroxaban 10 mg had lower total health-care costs than aspirin.

Topics: Anticoagulants; Aspirin; Cost Savings; Dose-Response Relationship, Drug; Drug Monitoring; Female; Health Care Costs; Hemorrhage; Humans; Male; Middle Aged; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Venous Thromboembolism

Topics: Aged; Brain Infarction; Endocarditis, Non-Infective; Factor Xa Inhibitors; Humans; Male; Rivaroxaban; Urinary Bladder Neoplasms; Venous Thromboembolism

Most clinical practice guidelines recommend low molecular weight heparin for the treatment of venous thromboembolism (VTE) in cancer patients. In the Hokusai VTE Cancer study, 1050 patients with cancer and acute VTE were randomized to oral edoxaban or subcutaneous dalteparin for at least 6 months and up to 12 months. Edoxaban was non-inferior to dalteparin with respect to the composite outcome of recurrent VTE and major bleeding. The rate of recurrent VTE was numerically lower, but the rate of major bleeding was significantly higher with edoxaban. The frequency of severe major bleeding was similar with edoxaban and dalteparin. The difference in major bleeding was mainly driven by a higher rate of upper gastrointestinal bleeding with edoxaban, especially in patients with gastrointestinal cancer. The pilot Select-D study randomized 406 patients with cancer and VTE to rivaroxaban or dalteparin for 6 months. Recurrent VTE was reduced, while both major and clinically relevant non major bleeding were significantly increased with rivaroxaban. Bleeding mostly involved the gastrointestinal tract and occurred in patients with gastroesophageal cancer. While waiting for ongoing studies on direct oral anticoagulants, the results of the Hokusai VTE Cancer suggest that edoxaban may represent a valuable alternative to low molecular weight heparin for the treatment of cancer-associated VTE. In patients with gastrointestinal cancer, the use of edoxaban requires careful benefit-risk weighting, taking into consideration patient's preferences.

Topics: Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Practice Guidelines as Topic; Pyridines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism

Topics: Anticoagulants; Antithrombins; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Neoplasms; Perioperative Care; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Hospitalization; Humans; Patient Discharge; Rivaroxaban; Venous Thromboembolism

Topics: Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Humans; Patient Discharge; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Guidelines as Topic; Humans; Recurrence; Risk Factors; Rivaroxaban; Venous Thromboembolism

Topics: Hospitalization; Humans; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Humans; Morpholines; Rivaroxaban; Thiophenes; Veins; Venous Thromboembolism

Topics: Anticoagulants; Aspirin; Humans; Recurrence; Rivaroxaban; Venous Thromboembolism

Rivaroxaban is a direct and selective inhibitor of factor Xa. The randomized clinical trials EINSTEIN evaluated the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE) proving that the drug was non-inferior to standard treatment. The aim of this survey was to describe how rivaroxaban was used in a group of "real-life" patients with VTE.. Between June and October 2014, physicians collected aggregate data, through an online questionnaire, on consecutive patients affected by VTE and treated with rivaroxaban in the previous 6 months. Descriptive statistics were performed on the collected data.. A total of 345 questionnaires were filled out. The mean age of patients was 62 years, with a low prevalence of concomitant diseases and/or pharmacological treatments. Deep vein thrombosis was diagnosed in 90% of patients and pulmonary embolism in 47%; only 48% was hospitalized. Rivaroxaban was prescribed at the recommended doses and/or regimen in no more than 60% of cases. In 96% of patients, the initial therapeutic plan did not require changes. Adherence to the therapeutic plan and overall patient satisfaction with therapy were high.. Rivaroxaban was found easy to use and was highly appreciated by patients.

Topics: Epidemiologic Studies; Factor Xa Inhibitors; Female; Health Care Surveys; Humans; Italy; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism

Deep vein thrombosis (DVT) and pulmonary embolism are collectively known as venous thromboembolism (VTE), which is a common vascular disease and a major cause of morbidity and mortality worldwide. We compare effectiveness and safety of rivaroxaban versus warfarin in a prospective cohort of routine care patients with incident unprovoked VTE.. In this propensity-matched cohort study, we linked nationwide Danish health registries to identify all patients with a first hospital diagnosis of unprovoked VTE who were new users of rivaroxaban or warfarin. Excluded patients included those who had not been residents in Denmark for at least 1 year before VTE diagnosis, patients with outpatient VTE diagnosis only, patients with other indications for oral anticoagulation treatment, patients with previous experience of oral anticoagulation, patients who did not have a prescription for rivaroxaban or warfarin within 7 days of VTE, and patients who redeemed prescriptions for both rivaroxaban and warfarin, or other oral anticoagulants. Primary effectiveness outcome was recurrent VTE and primary safety outcome was major bleeding. We used propensity matching and Cox regression to compare rates of the outcomes with rivaroxaban versus standard treatment.. From Dec 9, 2011, to Feb 28, 2016, we identified 29 963 patients with incident VTE. After exclusion, we identified 1734 propensity-matched patients given rivaroxaban (1751 before propensity matching) and 2945 propensity-matched patients given warfarin. The rate of recurrent VTE at 6 months' follow-up was 9·9 incidents per 100 person-years with rivaroxaban versus 13·1 incidents per 100 person-years with warfarin, yielding a hazard ratio (HR) of 0·74 (95% CI 0·56-0·96). The rate of major bleeding was 2·4 per 100 person-years at 6 months in rivaroxaban users versus 2·0 in warfarin users (HR 1·19, 95% CI 0·66-2·13).. In this clinical practice setting, rivaroxaban in patients with unprovoked VTE was associated with reduced risk of recurrent VTE compared with standard treatment, without compromising safety.. Obel Family Foundation.

Topics: Administration, Oral; Aged; Anticoagulants; Denmark; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Propensity Score; Prospective Studies; Pulmonary Embolism; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) is a major complication of malignant diseases and is a frequent cause of death in patients with cancer. Managing anticoagulation in these patients is challenging because of the high risk of recurrent VTE and bleeding events. Rivaroxaban is an oral anticoagulant that provides rapid onset of anticoagulation.. The aim of this study was to describe the complications of rivaroxaban and potentially associated factors in patients with gynecologic cancer and VTE.. This was an observational study in women with gynecological cancer who developed VTE and were treated with 15 and 20 mg rivaroxaban at Instituto Nacional de Câncer from July 2014 to July 2015.. Forty-one patients were treated with rivaroxaban. Most patients were younger than 60 years and presented cervical cancer; 58.5% of women did not have complications, thus remaining at a dose of 20 mg/d. Because of complications, 12.2% had the dose reduced to 15 mg/d, 12.2% had the drug suspended, 7.3% had progressive worsening of the disease with suspension of anticoagulation, and 9.8% progressed to death because of progression of the disease.. Rivaroxaban has been documented as a low-cost, easily controlled option compared with standard therapy. Most participants in this study had no complications. However, it was not possible to assess associations with statistical significance. Further analytical studies with larger samples are required to evaluate the safety and efficacy of this treatment in patients with gynecologic cancer.

Topics: Anticoagulants; Female; Genital Neoplasms, Female; Humans; Middle Aged; Rivaroxaban; Venous Thromboembolism

Topics: Antithrombins; Dabigatran; Humans; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Review Literature as Topic; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Vitamin K

Limited data is available regarding the pharmacological prophylaxis for venous thromboembolism (VTE) in Asian patients undergoing total knee arthroplasty or total hip arthroplasty (TKA/THA).. We performed a population-based epidemiological study using the Health Insurance Review and Assessment Service database to estimate the rate of pharmacological thromboprophylaxis and its impact on VTE in Korean patients who underwent TKA/THA between 2009 and 2013.. We identified 306,912 cases (TKA, 261,260; THA, 45,652). The pharmacological thromboprophylaxis rate was 57.16% (TKA, 58.32%; THA, 50.51%), which increased from 42.81% in 2009 to 65.92% in 2013 (P = 0.0165). Both low-molecular-weight-heparin (22.42%) and rivaroxaban (22.71%) were the most common drugs for prophylaxis. The number of patients aged ≥ 60 years (87.31% vs. 81.01%, P < 0.0001), cases requiring general anesthesia (20.70% vs. 18.37%, P < 0.0001), and cases requiring long hospital stay (median, 13 days vs. 12 days, P < 0.0001) were significantly greater in the pharmacological prophylaxis group. The incidence of VTE within 3 months of surgery was 1.52% (TKA, 1.46%; THA, 1.87%). Patients with pharmacological prophylaxis had higher VTE rates (TKA, 1.69% vs. 1.14%; THA, 2.30% vs. 1.43%) than those without prophylaxis, with advanced age, use of general anesthesia, and a longer hospital stay increasing the risk of VTE. However, rivaroxaban significantly reduced the incidence of VTE following TKA (0.82% vs. 1.14%; odd ratio [OR], 0.72; 95% CI, 0.65-0.79). Moreover, ≥ 10 days of pharmacological thromboprophylaxis was significantly associated with lower incidence of VTE after TKA (1.33% vs. 1.52%; OR, 0.87; 95% CI, 0.81-0.94).. This represents the largest epidemiological study showing a gradual increase in the use of pharmacological prophylaxis in Korean patients undergoing TKA/THA. Although the incidence of VTE is still low without pharmacological prophylaxis, this study demonstrates that the incidence of VTE can be reduced further using appropriate pharmacological thromboprophylaxis strategies.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Erythrocyte Transfusion; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Polysaccharides; Postoperative Complications; Postoperative Hemorrhage; Republic of Korea; Risk Factors; Rivaroxaban; Venous Thromboembolism

Topics: Drug Therapy, Combination; Eosinophilia; Factor Xa Inhibitors; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Prednisolone; Rivaroxaban; Skin Ulcer; Thigh; Venous Thromboembolism

Ander Cohen speaks to Adam Price-Evans, Commissioning Editor of Future Cardiology: Alexander (Ander) Cohen MBBS (Hons), MSc, MD, FRACP is a vascular physician and epidemiologist at Guy's and St Thomas' Hospital, King's College (London, UK). He graduated with honors in medicine and honors in surgery from the University of Melbourne, Australia, and became a fellow of the Royal Australasian College of Physicians in 1990. He was awarded an MSc in Epidemiology from the London School of Hygiene and Tropical Medicine, University of London in 1991 with a thesis on the metabolic syndrome in South-Asian populations. In 1998, he was awarded an MD with a thesis on the epidemiology of venous thromboembolism and thromboprophylaxis. In addition to his clinical work, he is involved in designing, managing and analyzing clinical trials from Phase I to IV. He is the Chairman and a member of many international steering committees for multicenter trials, epidemiological and pharmacoeconomic studies, and was previously the Director of Clinical Research and an Epidemiologist in Thrombosis Research at King's College Hospital.

Topics: Biomedical Research; Epidemiologists; Factor Xa Inhibitors; Humans; London; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Aspirin; Hemorrhage; Humans; Recurrence; Rivaroxaban; Venous Thromboembolism

The efficacy and safety or rivaroxaban versus enoxaparin/vitamin K antagonist for treatment and prevention recurrence of venous thromboembolism (VTE) was demonstrated in the randomised EINSTEIN trials. We assessed the effectiveness and safety of rivaroxaban versus warfarin in VTE patients managed in routine practice. Using US MarketScan claims from 1/2012-6/2015, we included adults with a primary diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) during a hospitalisation/emergency department visit, newly-initiated on rivaroxaban or warfarin within 30-days after the VTE and with ≥180-days of continuous medical/prescription benefits prior to the VTE (baseline). Patients with a claim for anticoagulation at baseline were excluded. Recurrent VTE, major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) were assessed. Differences in baseline characteristics between cohorts were adjusted for using inverse probability of treatment weights based on propensity-scores. Patients had a maximum of 12-months period of follow-up post-VTE or until endpoint occurrence, switch/discontinuation of index anticoagulation, insurance disenrollment or end-of-follow-up. Cox regression was performed and reported as hazard ratios (HRs) with 95 % confidence intervals (CIs). In total, 13,609 rivaroxaban and 32,244 warfarin users experiencing VTE were included. Rivaroxaban was associated with an 19 % (95 %CI=10-27 %) reduction in recurrent VTE and a 21 % (95 %CI=4-35 %) reduction in major bleeding hazard versus warfarin. Rivaroxaban was also associated with significantly decreased hazards of ICH (HR=0.40) and GIB (HR=0.72). Rivaroxaban appears to reduce patients' hazard of both recurrent VTE and major bleeding in routine practice. These results appear consistent with EINSTEIN and post-marketing registry studies.

Topics: Anticoagulants; Databases, Factual; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Pulmonary Embolism; Recurrence; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

Topics: Administration, Oral; Anticoagulants; Dabigatran; Glycosaminoglycans; Hemorrhage; Humans; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

The EINSTEIN-Extension trial showed that an extended rivaroxaban treatment significantly reduced the risk for venous thromboembolic (VTE) recurrence. The present study assessed the risk for VTE recurrence and major bleeding associated with extended rivaroxaban treatment in a clinical practice setting among patients with VTE.. A retrospective study was conducted using claims data from February 2011 to April 2015. It included adult patients who initiated rivaroxaban therapy within 7 days after their first VTE and who continuously used rivaroxaban for at least 3 months (index date: end of initial 3-month treatment). Categorized into discontinued and continued cohorts, patients were followed up from the index date until the end of continuous treatment (continued cohort) or end of data or reinitiation of oral anticoagulant therapy (discontinued cohort). Using inverse probability of treatment weights controlling for confounders, adjusted Kaplan-Meier rates of recurrent VTE and major bleeding events were compared.. The analysis showed that, compared with the discontinued cohort (n = 1,536), the continued cohort (n = 5,933) had a significantly lower VTE recurrence rate after an additional 3 months (0.70% vs 1.70%), 6 months (1.41% vs 2.34%), 9 months (1.82% vs 3.01%), and 12 months (1.97% vs 3.01%) of treatment (all, p < 0.05). The difference in the cumulative event rates for major bleeding was not statistically significant. Similar results were obtained in an analysis among patients with VTE receiving rivaroxaban for ≥6 months.. Our results suggest that, in clinical practice settings, patients with VTE who continued rivaroxaban therapy after the initial 3- or 6-month treatment period had a significantly lower risk for VTE recurrence without a statistically significant increased risk for major bleeding.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Rivaroxaban; Venous Thromboembolism; Young Adult

In the Hokusai-VTE trial, 733 patients were treated with the reduced dose edoxaban regimen, which maintained efficacy and safety compared with the 60 mg dose, and was safer than warfarin. The prophylactic doses of apixaban and rivaroxaban reduced the risk of recurrent venous thromboembolism (VTE) in the extended treatment trials. Dabigatran 110 mg was approved by the European Medicine Agency for VTE treatment. Further data from registries and real-world studies will help to clarify whether patients, with other specific characteristics, can benefit from the reduced dose of direct oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Dose-Response Relationship, Drug; Evidence-Based Medicine; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Warfarin

Due to limited evidence on the impact of rivaroxaban in clinical practice, we compared the effectiveness of rivaroxaban versus standard of care (SOC) among patients in the Veterans Health Administration.. Adult patients with continuous enrollment in a health plan with medical and pharmacy benefits for ≥12 months before and ≥3 months after an inpatient diagnosis of pulmonary embolism (PE) between October 1, 2011, and June 30, 2015, and a prescription claim for an anticoagulant during the index hospitalization, were included. SOC drugs were low-molecular-weight heparin, unfractionated heparin, and warfarin. Propensity score matching was used in comparing PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), hospital-acquired complications (HACs), health care resource utilization, and costs among patients receiving SOC versus rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HACs.. Among 6746 patients with PE, 208 received rivaroxaban, 4641 received SOC and 1897 received other anticoagulants. Most (95%) were male; 22% were black. After 1:3 propensity score matching, there were 203 rivaroxaban and 609 SOC patients. During the 90-day follow-up, rivaroxaban users had similar rates of PE-related outcomes, but fewer had experienced at least 1 HAC (10.3% vs 15.9%; P = 0.0506), resulting in better net clinical benefit (82.8% vs 71.1%; P = 0.001). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs 19.9; P = 0.0005), a similar rehospitalization rate (0.2 vs 0.3; P = 0.084), lesser inpatient costs (US $3501 vs $6189; P < 0.0001), lesser inpatient costs and lesser total costs ($10,545 vs $14,192; P = 0.0002). When the sample was limited to patients with low-risk PE, we found similar patterns.. Patients with PE prescribed rivaroxaban had similar PE-related outcomes, but fewer HACs and lesser total costs, than did patients on SOC.

Topics: Adolescent; Adult; Aged; Anticoagulants; Female; Health Care Costs; Hemorrhage; Heparin; Hospitalization; Humans; Inpatients; Male; Middle Aged; Propensity Score; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Veterans; Warfarin; Young Adult

Essentials Anticoagulants prevent venous thromboembolism but may be associated with greater bleeding risks. Bivariate analysis assumes a non-linear relationship between efficacy and safety outcomes. Extended full-dose betrixaban is favorable over standard enoxaparin in bivariate endpoint. Clinicians must weigh efficacy and safety outcomes in decision-making on thromboprophylaxis.. Background Among acutely ill hospitalized medical patients, extended-duration thromboprophylaxis reduces the risk of venous thromboembolism (VTE), but some pharmacologic strategies have been associated with greater risks of major bleeding, thereby offsetting the net clinical benefit (NCB). Methods To assess the risk-benefit profile of anticoagulation regimens, a previously described bivariate method that does not assume a linear risk-benefit tradeoff and can accommodate different margins for efficacy and safety was performed to simultaneously assess efficacy (symptomatic VTE) and safety (major bleeding) on the basis of data from four randomized controlled trials of extended-duration (30-46 days) versus standard-duration (6-14 days) thromboprophylaxis among 28 227 patients (EXCLAIM, ADOPT, MAGELLAN and APEX trials). Results Extended thromboprophylaxis with full-dose betrixaban (80 mg once daily) was superior in efficacy and non-inferior in safety to standard-duration enoxaparin, and showed a significantly favorable NCB, with a risk difference of - 0.51% (- 0.89% to - 0.10%) in the bivariate outcome. Extended enoxaparin was superior in efficacy and inferior in safety (bivariate outcome: 0.03% [- 0.37% to 0.43%]), whereas apixaban and rivaroxaban were non-inferior in efficacy and inferior in safety (- 0.20% [- 0.49% to 0.17%] and 0.23% [- 0.16% to 0.69%], respectively). Reduced-dose betrixaban did not show a significant difference in either efficacy or safety (0.41% [- 0.85% to 1.94%]). Conclusions In a bivariate analysis that assumes non-linear risk-benefit tradeoffs, extended prophylaxis with full-dose betrixaban was superior to standard-duration enoxaparin, whereas other regimens failed to simultaneously achieve both superiority and non-inferiority with respect to symptomatic VTE and major bleeding in the management of acutely ill hospitalized medical patients.

Topics: Acute Disease; Anticoagulants; Benzamides; Clinical Decision-Making; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Drug Administration Schedule; Enoxaparin; Hemorrhage; Hospitalization; Humans; Multivariate Analysis; Nonlinear Dynamics; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

Direct oral anticoagulants (DOACs) can be quantified using methods that can be performed in any clinical or research laboratory using manual or automated instrument platforms. Dabigatran etexilate, the oral direct thrombin inhibitor, can be quantified by drug-calibrated clot or chromogenic-based assays using either thrombin or ecarin as substrates. Oral direct anti-Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban, can be quantified with drug-calibrated anti-Xa kits or reagents as typically used for measuring heparins (unfractionated, low molecular weight, or pentasaccharides).

Topics: Administration, Oral; Antithrombins; Blood Coagulation; Dabigatran; Drug Monitoring; Endopeptidases; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombin Time; Venous Thromboembolism

Recent American, European and Dutch guidelines recommend indefinite anticoagulation after a diagnosis of unprovoked venous thromboembolism in the absence of a high bleeding risk. The recommended approach would be to only stop anticoagulant therapy after three months in patients with one or more untreatable risk factors for bleeding such as prior major bleeding, uncorrectable hypertension or deep thrombocytopenia. Vitamin K-antagonists and direct oral anticoagulants (DOACs) were found to protect against recurrent venous thromboembolism at cost of major bleedings, although at a lower frequency than the number of prevented thrombotic events. Due to the lower risk of major bleeding than associated with vitamin K-antagonists, DOACs are the preferred treatment option for the long term treatment of unprovoked venous thromboembolism. Apixaban is available in a reduced dose for long-term treatment, and rivaroxaban in a reduced dose was recently shown to be more effective than aspirin.

Topics: Anticoagulants; Aspirin; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Rivaroxaban; Venous Thromboembolism

To evaluate the impact of a rivaroxaban discharge initiative on the efficacy and safety of acute venous thromboembolism treatment in emergency department patients.. Patients discharged on rivaroxaban from the emergency department were provided extensive counseling along with a commercially-available medication dose pack by the ED pharmacist. Patients were contacted by phone until they had obtained outpatient follow-up and remained adherent to anticoagulation beyond the initial first month of treatment.. In this retrospective chart review over a thirteen month period, efficacy and safety outcomes were compared between patients with intervention versus those who received usual care. Efficacy was defined by reduced 90-day readmission rates due to nonadherence or treatment failure, and improved medication adherence beyond the first month from discharge. Safety was determined by comparing 90-day readmission rates due to bleeding or adverse event.. 41 patients received intervention with rivaroxaban, and 34 patients received usual care, with 76% prescribed rivaroxaban and remaining patients started on enoxaparin alone (6%) or enoxaparin plus warfarin (18%). Improved treatment efficacy in the intervention group was not found to be statistically significant. Safety outcomes were similar between the two groups.. Home treatment of acute VTE, facilitated by medication dose pack, is a promising tactic to ensure both immediate and long-term treatment efficacy and safety. Further studies are warranted to demonstrate clinical superiority of this intervention.

Topics: Administration, Oral; Directive Counseling; Factor Xa Inhibitors; Female; Humans; Male; Medication Adherence; Middle Aged; Patient Discharge; Patient Transfer; Retrospective Studies; Rivaroxaban; United States; Venous Thromboembolism

Role of prophylactic anticoagulation in acutely ill medical patients has been extensively probed with the development of guidelines which made it convenient for the physicians to adopt a particular anticoagulation regimen for thromboprophylaxis. Intermingled with the guidelines are the development of modern anticoagulants like direct factor Xa inhibitors which are being studied for their role in the prevention of venous thromboembolism (VTE) in medically ill patients and have been concluded so far with the positive note. We are going to discuss a case of a patient who was admitted in the medical ICU with hospital acquired pneumonia. As her immediate risk of VTE was low (Wells criteria), she was advised mechanical measures to prevent VTE along with continuation of rivaroxaban therapy which had already been prescribed for her avalvular atrial fibrillation. While mechanically ventilated, she developed pulmonary venous thromboembolism. It is the first case report of VTE in adequately anticoagulated patient with rivaroxaban.

Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Critical Illness; Factor Xa Inhibitors; Humans; Respiration, Artificial; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the accumulation of inflammatory factors in the lesions in venous thrombus. Matrix metalloproteinase (MMP) expression and activity were downregulated in rivaroxaban-treated rats with deep venous thrombus. Rivaroxaban inhibited the elasticity of the extracellular matrix and collagen-elastin fibers. On the whole, these results indicate that rivaroxaban attenuates deep venous thrombus through MMP-9-mediated NF-κB signaling pathway.

Topics: Animals; Disease Models, Animal; Fibrinolysis; Humans; Matrix Metalloproteinase 9; NF-kappa B; Rats; Rivaroxaban; Signal Transduction; Veins; Venous Thromboembolism; Venous Thrombosis

Anticoagulant-associated heavy menstrual bleeding (HMB) is an underrecognized but not uncommon problem in clinical practice. Premenopausal women should be advised of the potential effect of anticoagulant therapy on menstrual bleeding at the time of treatment initiation. Consequences of HMB should be assessed and treated on an ongoing basis. In the acute setting, the decision to withhold anticoagulants is based on an individual patient's risk of thrombosis and the severity of the bleeding. For women who require long-term anticoagulation, a levonorgestrel intrauterine system, tranexamic acid (during menstrual flow), high-dose progestin-only therapy, or combined hormonal contraceptives are effective for controlling HMB. The risk of thrombosis during anticoagulant therapy with these treatments is not well studied but is likely to be low. Selection of type of hormonal therapy is based on patient preference, other indications for and contraindications to therapy, adverse effect profile, and ongoing thrombotic risk factors. Women who do not respond to medical treatment or who do not wish to retain their fertility should be considered for surgical management.

Topics: Adult; Anticoagulants; Antifibrinolytic Agents; Dose-Response Relationship, Drug; Female; Humans; Menorrhagia; Practice Guidelines as Topic; Pulmonary Embolism; Rivaroxaban; Tranexamic Acid; Treatment Outcome; Venous Thromboembolism; Young Adult

Topics: Computed Tomography Angiography; Contraceptives, Oral, Combined; Factor Xa Inhibitors; Female; Humans; Pulmonary Embolism; Risk Factors; Rivaroxaban; Venous Thromboembolism; Young Adult

Direct oral anticoagulants (DOACs) became rapidly accepted as an alternative to warfarin in the prevention of stroke in atrial fibrillation and prophylaxis of thromboembolic events. Their safety and efficacy have been well documented in several studies, however, as with any new drug, use in real-world population often reveals risk factors that may affect treatment outcomes. The aim of the study was to determine the prescribing patterns and analyse patient characteristics to identify incidence of selected factors (age, weight, comorbidities and interacting medication) that may affect DOAC safety and efficacy. We conducted a 12-months retrospective study of 504 patients who were initiated DOAC in a large university hospital. Basic demographics, indication for DOAC prescribing, renal functions, co-medication, comorbidities and prescribing service were collected from the hospital's electronic records. Rivaroxaban accounted for the majority of DOAC prescriptions (58.9%), and prophylaxis of deep venous thromboembolism was the main reason for initiation of DOACs (58.7%). We found significant variability in terms of age (16 - 96 years) and weight (34.5 - 184 kg). Chronic renal failure was present in 5.6% of patients. We identified 101 clinically relevant drug interactions of DOACs, mostly with selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (31.7%) and nonsteroidal anti-inflammatory drugs (28.7%). Only three drug interactions were rated as contraindicated. Hypertension (48.6%), dyslipidaemia (33.1%), musculoskeletal disorders (21.0%) and diabetes mellitus (16.1%) were the most frequent comorbidities. Clinicians should be careful when prescribing DOACs to patients with comorbidities or co-medication that have the potential to increase risk of bleeding or decrease anticoagulant activity of DOACs.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Drug Interactions; Female; Hospitals, Teaching; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism; Young Adult

Pharmacologic agents for the treatment and prevention of venous thromboembolism in the cancer patient population are limited. Currently, low-molecular-weight heparin is recommended by national consensus guidelines for this indication. Rivaroxaban, an oral factor Xa inhibitor, is Food and Drug Administration (FDA) approved for the treatment and prevention of venous thromboembolism and offers the convenience of oral fixed-dose regimens, no routine laboratory monitoring, and has few drug and dietary interactions; however, its use in patients with cancer has not been largely studied. We report 2 cases of recurrent venous thromboembolism in patients with active cancer on rivaroxaban therapy. The first case is a 64-year-old female admitted for recurrent pulmonary embolism, and the second case is a 70-year-old female admitted for recurrent deep vein thrombosis. Both patients were receiving rivaroxaban at the time of thromboembolic recurrence. These cases serve as a reminder to health-care providers that more safety and efficacy data in the cancer patient population are needed prior to using rivaroxaban for venous thromboembolism treatment.

Topics: Aged; Factor Xa Inhibitors; Female; Humans; Middle Aged; Neoplasms; Rivaroxaban; Venous Thromboembolism

Treatment of venous thromboembolism (VTE) has been confined to parenteral agents and oral vitamin K antagonists for decades; however, with the approval of the direct oral anticoagulants (DOACs), clinicians now have more options. This study aims to evaluate the real world prescribing practices of all oral anticoagulants for VTE at a single center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 105 patients included in the analysis, 45 (43 %) patients received warfarin and 60 (57 %) patients received a DOAC. Rivaroxaban and apixaban were the most common DOACs initiated. There were significantly more patients in the warfarin group with an eCrCl of <60 ml/min compared to patients who received a DOAC (77.8 % vs. 15 %; P < 0.05). There were significantly less patients in the warfarin group with serum aminotranferase concentrations three times the upper limit of normal compared to those who received a DOAC (15.6 % vs. 55 %; P < 0.05). Patients who received a DOAC had less days on parenteral anticoagulation compared to patients who received warfarin (median 2.5 days [IQR 0-4] vs. 6 days [IQR 5-7], p < 0.05). Patients who received a DOAC had a shorter hospital length of stay compared to patients who received warfarin (median 3 days [IQR 2-4] vs. 8 days [IQR 6-10], p < 0.05). This analysis showed that DOACs are being prescribed more than warfarin for treatment of new onset VTE. Renal and liver function may influence the agent prescribed. Utilization of DOACs may decrease the hospital length of stay.

Topics: Acute Disease; Adult; Anticoagulants; Cohort Studies; Female; Humans; Length of Stay; Male; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Transaminases; Venous Thromboembolism; Warfarin

: Activated protein C resistance (APC-R) is assessed as part of thrombophilia screening, preferably in patients not taking oral anticoagulants. Rivaroxaban is known to alter some APC-R assays. To our knowledge, there have been no reports on the effect of rivaroxaban on the Russell viper venom time (RVVT)-based APC-R assay in real-life patients. In 168 consecutive outpatients suspected of having venous thromboembolism because of thrombophilia, APC-R was determined using the RVVT-based ProC Ac R assay (Siemens, Marburg, Germany). Patients receiving rivaroxaban or vitamin K antagonists were eligible. We measured rivaroxaban concentrations using the anti-Xa Biophen DiXal assay (Hyphen Biomed, Neuville-Sur-Oise, France) and factor V Leiden using the real-time PCR. APC-R was detected in 23 (28%) patients on rivaroxaban (n = 81) administrated 2-48 h since the blood draw, 15 (28%) patients on vitamin K antagonists (n = 54), and in four (12%) patients off anticoagulation (n = 33). Compared with nonanticoagulated patients, APC-R ratios were similar in patients on rivaroxaban, without any correlation with rivaroxaban concentrations (from 0 to 303 μg/l). None of the patients on rivaroxaban were found to have false-negative or false-positive APC-R ratios. Rivaroxaban concentrations up to 300 μg/l do not affect results of the ProC Ac R RVVT-based assay, which could be recommended in patients referred to a clinic for thrombophilia screening in whom the time since the last dose of rivaroxaban is uncertain.

Topics: Activated Protein C Resistance; Adult; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Prothrombin Time; Rivaroxaban; Thrombophilia; Venous Thromboembolism; Vitamin K

Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4-7.4 %), major bleeding was 2.2 % (95 % CI = 0-4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7-23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.

Topics: Anticoagulants; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Rivaroxaban has been shown to have similar efficacy but less major bleeding than warfarin in randomized trials of patients experiencing venous thromboembolism (VTE). This report sought to assess healthcare costs up to 12-months following an index VTE in patients prescribed either rivaroxaban or warfarin.. This study analyzed claims from the MarketScan Commercial Claims and Encounters Database from November 2011-July 2015. It selected adults newly-diagnosed with VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) if they had an outpatient prescription claim for rivaroxaban or warfarin within 7-days of the index event. Warfarin users were 2:1 propensity-score matched to rivaroxaban users and followed until the end of insurance coverage, end of data availability or 12-months of follow-up. Total per patient healthcare costs, including inpatient, outpatient, and overall pharmacy costs, were compared using a multivariable generalized linear model.. In total, 10,929 rivaroxaban patients were matched to 21,858 warfarin patients. Mean follow-up for rivaroxaban and warfarin patients was 317- and 321-days for those experiencing an index DVT, and 313- and 318-days for those with PE. Mean overall treatment costs per patient were lower for rivaroxaban vs warfarin users (-$1,116, p = .0016). This cost difference was driven by lower inpatient (-$622) and outpatient (-$1,156) treatment costs, and the higher pharmacy costs ($661) were, therefore, fully offset. Results were similar when analysis was restricted to DVT patients. No significant difference in total costs was observed in patients experiencing an index PE.. Claims databases are subject to inaccuracies and missing data. Prescription claims may not fully reflect actual medication utilization. Despite propensity-score matching and regression, residual confounding cannot be excluded.. Rivaroxaban was associated with significantly lower total per patient VTE treatment costs, despite higher pharmacy costs. These savings are the result of decreased inpatient and outpatient healthcare utilization costs associated with rivaroxaban.

Topics: Adult; Anticoagulants; Databases, Factual; Factor Xa Inhibitors; Female; Health Expenditures; Humans; Male; Middle Aged; Propensity Score; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Warfarin

This study aimed to provide safety and efficacy data of rivaroxaban in routine patient care in a non-selected symptomatic venous thromboembolism (VTE) population.. REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with oral rivaroxaban, VKA or parenteral heparin/fondaparinux alone for at least 3months and who are followed up for 6months. From Nov. 2013 to July 2015, 499 consecutive patients were retained for baseline analysis and 445 for safety analysis. The mean age was 65.1years, 7.6% had previously known active cancer, 18.6% had creatinine clearance 30≤CrCl<60mL/min, and 87.8% had pulmonary embolism with or without deep venous thrombosis. The major and clinically relevant bleeding rate was 5.4% (15/280) in the rivaroxaban group, 9.4%/(9/96) in the VKA group and 7.2% (5/69) in the heparin/fondaparinux group. The recurrent VTE rate was 1.4% (4/280) in the rivaroxaban group, 3.1% (3/96) in the VKA group and 11.6% (8/69) in the heparin/fondaparinux group. In the propensity score-adjusted samples, major and clinically relevant non-major bleeding (HR 0.37 [95% CI, 0.15 to 0.93], p<0.05), all-cause death (HR 0.21 [95% CI, 0.06 to 0.66], p<0.01) and the composite of recurrent VTE, major and clinically relevant non-major bleeding and all-cause mortality (HR 0.35 [95% CI, 0.17 to 0.71], p<0.01), were significantly lower in the rivaroxaban group compared to the VKA group.. In REMOTEV 6-month outcomes are consistent with the findings of the phase 3 randomized trials and post-marketing data, with low rates of major bleeding and symptomatic recurrent VTE.

Topics: Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Registries; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

This study investigated the effectiveness and the outcomes of rivaroxaban vs the standard of care for venous thromboembolic prophylaxis in patients undergoing fracture-related surgery. A total of 413 patients undergoing fracture-related surgery from 9 Swiss orthopedic and trauma centers were enrolled. The authors selected the type of venous thromboembolic prophylaxis according to standardized medical practice at the participating centers before the inclusion of patients: 208 patients received rivaroxaban and 205 received the standard of care. Data on symptomatic thromboembolic and bleeding events, surgery-related complications, death, adverse events, time to mobilization, and hospital discharge were collected. Symptomatic thromboembolic events were reported in 1 patient (0.5%) and 2 patients (1.0%) and treatment-emergent major bleeding events were reported in 1 patient (0.5%) and 2 patients (1.0%) receiving rivaroxaban and the standard of care, respectively. The durations of hospital stay and venous thromboembolic prophylaxis were similar in the 2 groups. In both groups, adverse events related to venous thromboembolic prophylaxis were reported in 12 patients. The proportion of patients with minor and major fracture surgery was 74.3% and 25.7%, respectively. In patients undergoing minor fracture surgery receiving rivaroxaban (n=167) and the standard of care (n=140), no symptomatic thromboembolic events and no major bleeding events were reported. Outcomes of this study indicate that rivaroxaban might be an appropriate oral alternative for venous thromboembolic prophylaxis in routine medical care after fracture-related major and minor surgery. Reported results were comparable to those from other large-scale, noninterventional and randomized controlled studies. [Orthopedics. 2017; 40(2):109-116.].

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Factor Xa Inhibitors; Female; Fracture Fixation; Fractures, Bone; Humans; Male; Middle Aged; Perioperative Care; Postoperative Complications; Rivaroxaban; Switzerland; Treatment Outcome; Venous Thromboembolism; Young Adult

The factor Xa inhibitors have been widely used for the treatment and prevention of venous thromboembolism (VTE). However, the efficacy of factor Xa inhibitors in Japanese patients with VTE has not been well examined. In this study, we investigated the effect of the sequential use of two factor Xa inhibitors in patients with acute VTE.. We conducted an observational study of 87 consecutive patients diagnosed with VTE. As an initial treatment, we administered subcutaneous fondaparinux to the patients for 7-10 days, and then switched to oral rivaroxaban. The symptoms and findings were assessed after the initial treatment and after using rivaroxaban for 7-14 days. We evaluated the deep vein thrombosis (DVT) in the legs using our own scoring system [quantitative ultrasound thrombosis (QUT) score].. Of the 87 patients, 33% had symptoms, half had pulmonary embolism (PE), and 95% had DVT of the legs. Out of the 87 patients, VTE worsened during the administration of fondaparinux in 4 patients. All of them had experienced malignancy, and died within 6 months. Of two patients developing bleeding, one patient required a transfusion. Eventually, this strategy was effective in 80 patients and had no change in one. The D-dimer level was significantly reduced by fondaparinux (17.8μg/ml±16.0μg/ml vs. 8.3μg/ml±7.2μg/ml, p<0.0001), followed by rivaroxaban (8.3μg/ml±7.2μg/ml vs. 5.5μg/ml±4.9μg/ml, p<0.0001). Similarly, the QUT score was improved by fondaparinux (4.7±2.6 vs. 2.5±2.5, p<0.0001), and further reduced by rivaroxaban (2.5±2.5 vs. 1.9±1.8, p<0.0001).. A treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute VTE in Japanese patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

The aim of this study was to evaluate the cost-effectiveness of rivaroxaban and apixaban versus enoxaparin for the universal prophylaxis of venous thromboembolism (VTE) and associated long-term complications in Chinese patients after total hip replacement (THR).. A decision model, which included both acute VTE (represented as a decision tree) and the long-term complications of VTE (represented as a Markov model), was developed to assess the economic outcomes of the three prophylactic strategies for Chinese patients after THR. Transition probabilities for acute VTE were derived from two randomized controlled studies, RECORD1 and ADVANCE3, of patients after THR. The transition probabilities of long-term complications after acute VTE, utilities, and costs were derived from the published literature and local healthcare settings. One-way and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty concerning the model parameters. The quality-adjusted life years (QALYs) and direct medical costs were reported over a 5-year horizon, and incremental cost-effectiveness ratios (ICERs) were also calculated.. Thromboprophylaxis with apixaban was estimated to have a higher cost (US $178.70) and more health benefits (0.0025 QALY) than thromboprophylaxis with enoxaparin over a 5-year time horizon, which resulted in an ICER of US $71,244 per QALY gained and was more than three times the GDP per capita of China in 2014 (US $22,140). Owing to the higher cost and lower generated QALYs, rivaroxaban was inferior to enoxaparin among post-THR patients. The sensitivity analyses confirmed these results.. The analysis found that apixaban was not cost-effective and that rivaroxaban was inferior to enoxaparin. This finding indicates that compared with enoxaparin, the use of apixaban for VTE prophylaxis after THR does not represent a good value for the cost at the acceptable threshold in China; in addition, the cost of rivaroxaban was higher with lower QALYs.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; China; Cost-Benefit Analysis; Decision Trees; Enoxaparin; Humans; Long Term Adverse Effects; Postoperative Complications; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

To study the safety and efficacy of rivaroxaban-a direct oral anticoagulant-use in patients with active cancer and venous thromboembolism (VTE).. Retrospective cohort study of 400 patients with active cancer and associated VTE, defined as deep venous thrombosis and/or pulmonary embolism. This single-center study was carried out from January 2012 to June 2015. The aim of this study was to determine the efficacy and safety, using the incidence of recurrent symptomatic VTE and major bleeding, respectively, throughout the treatment with rivaroxaban.. Of the 400 patients enrolled, 223 (55.8%) were female. A total of 362 (90.5%) patients had solid tumors and 244 (61%) had metastatic disease. A total of 302 (75.5%) received initial parenteral therapy with enoxaparin (median: 3, mean: 5.6, standard deviation [SD]: 6.4 days) followed by rivaroxaban. Ninety-eight patients (24.5%) were treated with on label rivaroxaban treatment. Recurrence rates were 3.25% with major bleeding occurring in 5.5% during the anticoagulant therapy (median: 118, mean: 163.9, SD: 159.9 days).. Rivaroxaban can be an attractive alternative for the treatment of cancer-associated thrombosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Recurrence; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Young Adult

To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.. Patients older than 18 years who received at least one dose of rivaroxaban the morning following surgery, adjusted dose warfarin, or adjusted dose warfarin with the addition of enoxaparin for VTE prophylaxis after major orthopedic surgery between October 1, 2011, and February 28, 2015, were included. Data collected from the electronic health record included patient demographics, renal function, inpatient aspirin, P2Y12 inhibitor and/or nonsteroidal antiinflammatory drug (NSAID) use, type of surgery, postoperative analgesia, and presence of VTE risk factors. Adjusted incidence rate ratio for bleeding or VTE events was estimated using modified Poisson regression with robust standard errors. Covariates included in a multivariable model were age, sex, aspirin use, P2Y12 inhibitor use, NSAID use, obesity, VTE risk factors, and creatinine clearance.. There were 3246 patients who met study inclusion criteria. Overall, incidences of bleeding and VTE events were rare. Bleeding event incidence ranged from 0.4% in the warfarin and warfarin with the addition of enoxaparin groups to 1.2% in the rivaroxaban group (p=0.088). There were two major bleeding events and 18 minor bleeding events (including hemorrhagic wound complications). VTE event incidence ranged from 0.2% in the warfarin with the addition of enoxaparin group to 0.6% in the rivaroxaban group (p=0.230). Two deep vein thromboses and 10 pulmonary emboli occurred. With use of the multivariable model, the warfarin and warfarin with the addition of enoxaparin groups had significantly lower incidence rates of bleeding compared with rivaroxaban (incidence rate ratio [IRR] = 0.218, p=0.0120, and IRR = 0.242, p=0.021, respectively).. We observed a small, yet significant, increase in rivaroxaban-related bleeding in the immediate postoperative period relative to warfarin or warfarin with the addition of enoxaparin for the prevention of VTE after major orthopedic surgery.

Topics: Aged; Anticoagulants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Hospitals, Community; Humans; Male; Middle Aged; Orthopedic Procedures; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

: The aim of the study was to investigate whether treatment with non-vitamin K antagonist oral anticoagulants (NOACs) is effective and well tolerated in real-life patients following venous thromboembolism (VTE) associated with severe inherited thrombophilia. We evaluated 33 consecutive patients with severe inherited thrombophilia, defined as the presence of deficiencies in protein C, protein S, or anti-thrombin, homozygous factor V Leiden and prothrombin G20210A mutations, or combined defects. The patients were recruited from March 2010 to December 2015 and followed till July 2016. Rivaroxaban was used in 23 patients (70%), whereas dabigatran and apixaban were used in 4 patients each. During a median 21 (range 8-34) months' follow-up, three recurrent VTE episodes (9%) were observed. Deep vein thrombosis recurred after 6 months on rivaroxaban in a protein S-deficient 32-year-old woman who had heavy menstrual bleeding resulting in interruptions of therapy. A long journey preceded deep vein thrombosis recurrence after 12 months of rivaroxaban use in a 59-year-old obese man homozygous for prothrombin 20210A mutation. The third recurrent VTE following anticoagulation withdrawal prior to surgery and during hospitalization was observed in a 56-year-old woman with protein S deficiency and heterozygous factor V Leiden. The three patients continued use of NOACs, apixaban, dabigatran, and rivaroxaban, respectively. This largest real-life series of patients with severe thrombophilia receiving NOACs indicates that such patients could be safely and effectively treated with NOACs. Lower efficacy was observed in protein S deficiency. Recurrent VTE was mostly related with nonadherence, which highlights an important role of regular intake of NOACs in high-risk patients.

Topics: Adult; Anticoagulants; Dabigatran; Female; Humans; Male; Medication Adherence; Middle Aged; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thrombophilia; Venous Thromboembolism; Young Adult

Unlike rivaroxaban, treatment of patients with pulmonary embolism (PE) with warfarin requires parenteral bridging and coagulation monitoring that may prolong length-of-stay (LOS) and increase hospital costs.. The aim of this study was to compare LOS, hospital costs and readmissions in PE patients managed through observation stays treated with rivaroxaban or parenterally bridged warfarin.. Premier Hospital claims data from November 2012 to March 2015 were used to identify patients with a primary diagnosis code for PE managed through an observation stay and with ≥1 claim for a PE-related diagnostic test on day 0-2. Rivaroxaban users, allowing ≤2 days of prior parenteral therapy, were 1:1 propensity-score matched to patients receiving parenterally bridged warfarin. LOS, the proportion of encounters lasting >2 midnights, total hospital costs of the index visit and risk of readmission for venous thromboembolism (VTE) or major bleeding during the same month or 2 months subsequent to the index event were compared between matched cohorts using multivariable regression.. A total of 312 rivaroxaban users were matched to 312 patients receiving parenterally bridged warfarin. Rivaroxaban was associated with an average of 0.27-day shorter LOS, a 52% decreased odds of an encounter lasting >2 midnights and a $403 mean reduction in costs vs parenterally bridged warfarin (P≤.002 for all). The readmission rate for VTE during the same or subsequent 2 months following the index PE was similar between cohorts (P=.75). No patient in either cohort was readmitted for major bleeding.. Rivaroxaban was associated with shortened LOS and lowered cost vs parenterally bridged warfarin in PE observation stay patients, without increases in the short-term rate of complications or readmission.

Topics: Administrative Claims, Healthcare; Adult; Aged; Anticoagulants; Female; Hemorrhage; Hospital Costs; Humans; Length of Stay; Male; Middle Aged; Observation; Patient Readmission; Propensity Score; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Warfarin

The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events. This document represents a consensus paper on the use of DOACs by representatives of three Italian scientific societies: the Italian Society of Internal Medicine (SIMI), the Federation of the Associations of Hospital Managers (FADOI), and the Society for the Study of Haemostasis and Thrombosis (SISET). This document formulates expert opinion guidance for pragmatic managing, monitoring and reversing the anticoagulant effect of DOACs in both chronic and emergency settings. This practical guidance may help the internist to create adequate protocols for patients hospitalized ion internal medicine wards, where patients are often elderly subjects affected by poly-morbidities and renal insufficiency, and, thus, require particular attention to drug-drug interactions and peri-procedural protocols.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Competence; Consensus; Dabigatran; Drug-Related Side Effects and Adverse Reactions; Factor Xa Inhibitors; Food-Drug Interactions; Humans; Internal Medicine; Italy; Liver Diseases; Perioperative Period; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Time Factors; Venous Thromboembolism

Topics: Factor Xa Inhibitors; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism

Essentials Studies evaluating the procedural interruption of direct oral anticoagulants (DOACs) are lacking. We conducted a study of the interruption of DOACs for prior venous thromboembolic disease (VTE). The post-operative risks of recurrent VTE and major bleeding are low in this patient population. A scheme based on half-life and procedure-related bleeding appears safe and efficacious.. Background Direct oral anticoagulants (DOACs) are increasingly being used in the setting of venous thromboembolic disease (VTE). There is little evidence to guide the peri-procedural interruption of DOACs in this patient population. A number of studies have evaluated the perioperative interruption of DOACs based on half-life of the anticoagulant and the underlying procedural bleeding risk in patient with atrial fibrillation, but it remains unclear whether these findings can be extended to patients with VTE. Objective Evaluate thrombotic and bleeding outcomes following the perioperative interruption of direct oral anticoagulation in patients with prior VTE. Methods We conducted a retrospective analysis of consecutive patients on a DOAC for prior VTE requiring temporary interruption of anticoagulation for an invasive procedure. The primary efficacy outcome was the 30-day symptomatic VTE rate, and the primary safety outcome was the 30-day major bleeding rate. Secondary outcomes included overall mortality and the rate of clinically relevant non-major bleeding. Results A total of 190 patients were included in the analysis. The 30-day VTE rate was 1.05% (95% CI, 0.29-3.8%) and the 30-day major bleeding rate was 0.53% (95% CI, 0.09-2.93%). There were no deaths during the 30-day follow-up period. The rate of clinically relevant non-major bleeding was 3.16% (95%CI , 1.46-6.72%). Conclusions The perioperative interruption of DOACs in the setting of VTE, using a strategy that considers the half-life of the DOAC and the underlying procedural bleeding risk, appears to be both safe and effective.

Topics: Administration, Oral; Aged; Antithrombins; Blood Coagulation; Dabigatran; Drug Administration Schedule; Factor Xa Inhibitors; Female; Half-Life; Humans; Male; Middle Aged; Perioperative Care; Postoperative Hemorrhage; Pyrazoles; Pyridones; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Surgical Procedures, Operative; Time Factors; Treatment Outcome; Venous Thromboembolism

The approval of rivaroxaban has changed the landscape of treatment of venous thromboembolism (VTE). Little is known about the effect of rivaroxaban compared with vitamin K antagonists (VKA), when used in the everyday clinical practice. The aim of this study was to investigate the safety and effectiveness of rivaroxaban compared with VKAs among patients with VTE, using the Danish nationwide registries. All patients diagnosed with VTE and treated with either rivaroxaban or VKAs between 2013 and 2015 were included. A total of 12,318 patients were diagnosed with VTE and treated with VKAs [n=6,907] or rivaroxaban [n=5,411.]. Combined Cox regression analyses showed that the standardised absolute six-month risk of recurrent VTE was 3.03 % [95 % CI: 2.57 % to 3.48 %] in the rivaroxaban group and 3.13 % [95 % CI: 2.70 % to 3.56 %] in the VKA group (absolute risk difference of -0.11 % [95 % CI: -0.76 % to 0.54 %]). The standardised absolute six-months risk of bleeding was 2.28 % [95 % CI: 1.87 % to 2.67 %] for patients in the rivaroxaban group and 2.10 % [95 % CI: 1.78 % to 2.43 %] in the VKA group (absolute risk difference of 0.18 % [95 % CI: -0.34 % to 0.67]). In conclusion, rivaroxaban was associated with similar risk of recurrent VTE and bleeding compared with VKA.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Comorbidity; Denmark; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Recurrence; Registries; Risk; Rivaroxaban; Venous Thromboembolism; Vitamin K; Young Adult

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Drug Administration Schedule; Drug Monitoring; Hemorrhage; Humans; Retrospective Studies; Rivaroxaban; Spain; Venous Thromboembolism

Abdominoplasty, a commonly performed aesthetic procedure, is considered to have an increased risk of venous thromboembolism (VTE) events. At present, routine VTE chemoprophylaxis following abdominoplasty remains controversial.. This study evaluates the authors' experience with rivaroxaban, an oral Factor Xa inhibitor, for VTE prophylaxis in abdominoplasty patients.. A retrospective case series was conducted. All patients who underwent abdominoplasty and received rivaroxaban were included. The prophylactic dose was 10 mg daily for 7 days, beginning 12 hours postoperatively. Patient demographics, comorbidities, and type of surgery were recorded. The primary outcome measured was hematologic complication, including VTE, hematoma requiring operative evacuation, and need for blood transfusion.. From September 2012 until July 2014, 132 patients (122 women and 10 men) underwent abdominoplasty surgery and received rivaroxaban postoperatively. Mean patient age was 43.7 years, and mean body mass index was 27.1. One hundred twenty-five patients also underwent abdominal muscle plication. Eleven patients underwent a fleur de lis vertical skin resection component. One hundred patients underwent concomitant abdominal liposuction, while 79 patients also had back liposuction. Only 1 patient had a symptomatic VTE event. Three patients had a hematoma requiring operative evacuation, and all went on to heal without sequelae. Two patients received a blood transfusion for anemia during their course of rivaroxaban.. Oral rivaroxaban administration for chemoprophylaxis in abdominoplasty patients is safe, with low rates of symptomatic VTE and hematoma formation. The authors continue routine use of the medication for patients at increased risk for VTE events. LEVEL OF EVIDENCE 4: Risk.

Topics: Abdominoplasty; Adult; Aged; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Young Adult

Topics: Abdominoplasty; Anticoagulants; Humans; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

Few studies have identified patterns and predictors of use of direct oral anticoagulants for venous thromboembolism (VTE).. To describe the use of anticoagulants and assess predictors associated with the prescription of rivaroxaban over vitamin K antagonist (VKA) for the subsequent treatment of VTE.. This cross-sectional study was built with all consecutive patients newly diagnosed with acute VTE admitted between February 18, 2013, and September 18, 2013, in an academic tertiary care center in Quebec, Canada. Patient characteristics and VTE treatments were described. Univariate analyses and a multiple forward stepwise logistic regression were performed to assess predictors of rivaroxaban use over VKA for the subsequent treatment of VTE.. The study included 256 patients, 36.7% with a diagnosis of deep vein thrombosis (DVT) and 63.3% with pulmonary embolism (PE). Mean age was 63.1 years, and 28.1% of patients had cancer-associated VTE. Overall, rivaroxaban was prescribed in 1.6% of patients for the initial treatment and in nearly 20% of patients for the subsequent treatment of VTE. Low-molecular-weight heparin and VKA were mostly prescribed. Independent predictors associated with the prescription of rivaroxaban over VKA were as follows: age < 65 years (OR: 2.86, 95% CI 1.29-6.37), a diagnosis of DVT versus PE (OR 2.54, 95% CI 1.20-5.40), and an emergency department visit rather than a hospitalization (OR 2.24, 95% CI 1.06-4.71).. Several months following its availability, rivaroxaban was rarely prescribed for acute VTE disease. It also appears to be prescribed in different patient populations than VKA.

Topics: Anticoagulants; Cross-Sectional Studies; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism; Warfarin

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration.

Topics: Adult; Anticoagulants; Contraceptives, Oral, Hormonal; Drug Synergism; Enoxaparin; Estrogen Replacement Therapy; Estrogens; Female; Humans; Middle Aged; Progestins; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Rivaroxaban; Uterine Hemorrhage; Venous Thromboembolism; Young Adult

Outpatient treatment of acute venous thromboembolism (VTE) requires the selection of patients with a low risk of bleeding during the first few weeks of anticoagulation. The accuracy of four systems, originally derived for predicting bleeding in VTE treated with vitamin K antagonists (VKAs), was assessed in VTE patients treated with rivaroxaban.. All patients treated with rivaroxaban in the multinational EINSTEIN deep vein thrombosis (DVT) and pulmonary embolism (PE) trials were included. Major bleeding was defined as ≥2 g/dL drop in hemoglobin or ≥2-unit blood transfusion, bleeding in critical area, or bleeding contributing to death. The authors examined the incidence of major bleeding in patients with low-risk assignment by the systems of Ruiz-Gimenez et al. (score = 0 to 1), Beyth et al. (score = 0), Kuijer et al. (score = 0), and Landefeld and Goldman. (score = 0). For clinical relevance, the definition of low risk for all scores except Kuijer includes all patients < 65 years with no prior bleeding history and no comorbid conditions (current cancer, renal insufficiency, diabetes mellitus, anemia, prior stroke, or myocardial infarction).. A total of 4,130 patients (1,731 with DVT only, 2,399 with PE with or without DVT) were treated with rivaroxaban for a mean (±SD) duration of 207.6 (±95.9) days. Major bleeding occurred in 1.0% (40 of 4,130; 95% confidence interval [CI] = 0.7% to 1.3%) overall. Rates of major bleeding for low-risk patients during the entire treatment period were similar: Ruiz-Gimenez et al., 12 of 2,622 (0.5%; 95% CI = 0.2% to 0.8%); Beyth et al., nine of 2,249 (0.4%; 95% CI = 0.2% to 0.8%); Kuijer et al., four of 1,186 (0.3%; 95% CI = 0.1% to 0.9%); and Landefeld and Goldman, 11 of 2,407 (0.5%; 95% CI = 0.2% to 0.8%). At 30 days, major bleed rates for low-risk patients were as follows: Ruiz-Gimenez et al., five of 2,622 (0.2%; 95% CI = 0.1% to 0.4%); Beyth et al., five of 2,249 (0.2%; 95% CI = 0.1% to 0.5%); Kuijer et al., three of 1,186 (0.3%; 95% CI = 0.1% to 0.7%); and Landefeld and Goldman, seven of 2,407 (0.3%; 95% CI = 0.1% to 0.6%). No low-risk patient had a fatal bleed.. Four scoring systems that use criteria obtained in routine clinical practice, derived to predict low bleeding risk with VKA treatment for VTE, identified patients with less than a 1% risk of major bleeding during full-course treatment with rivaroxaban.

Topics: Aged; Anticoagulants; Clinical Decision-Making; Emergency Service, Hospital; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Predictive Value of Tests; Pulmonary Embolism; Risk Assessment; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data about rivaroxaban use in routine clinical practice are needed.. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007.. Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 [95% CI 0·54-1·54], p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 [95% CI 0·24-1·07], p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 [36·0%] of 2619 in the rivaroxaban group vs 805 [37·5%] of 2149 in the standard anticoagulation group).. In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings.. Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1 to 4 trials compared rivaroxaban 10 mg daily with commonly used doses of enoxaparin and demonstrated similar rates of VTE and bleeding.. To evaluate bleeding events between patients who received enoxaparin or rivaroxaban for prevention of venous thromboembolism (VTE) following total hip arthroplasty (THA) or total knee arthroplasty (TKA).. Retrospective cohort that compared patients undergoing THA and TKA who received enoxaparin (enoxaparin) with those who received rivaroxaban (rivaroxaban) and also with those who received enoxaparin in the RECORD 1 to 4 trials (enoxaparin RECORD). The primary outcome was any postoperative bleeding, defined as a composite of major and clinically relevant nonmajor bleeding based on the definitions in the RECORD 1 to 4 trials.. There was a lower rate of any postoperative bleeding (2.2% vs 6.8%, P = 0.004) in patients who received enoxaparin compared with rivaroxaban, and bleeding rates between the enoxaparin group and the enoxaparin RECORD groups were similar (2.2% vs 2.5%, P = 0.085). Major bleeding in the enoxaparin group (0.2%) was not significantly different from that in the rivaroxaban group (1.4%, P = 0.12) or the RECORD group (0.2%, P = 0.93). Clinically relevant nonmajor bleeding was also lower in the enoxaparin group compared with the rivaroxaban group (2.0% vs 5.5%, P = 0.012).. The use of enoxaparin for VTE prophylaxis following THA and TKA was associated with a lower rate of the primary outcome (any postoperative bleeding) compared with the use of rivaroxaban in a similar cohort of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Humans; Male; Middle Aged; Postoperative Hemorrhage; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Young Adult

The purpose of this study is to evaluate the efficacy and safety of rivaroxaban in patients with venous thromboembolism and active malignancy, given the paucity of clinical data with the use of direct Xa inhibitors in this high-risk population.. Consecutive patients treated with rivaroxaban for deep vein thrombosis or pulmonary embolism, enrolled into Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry between March 1, 2013, and April 30, 2015, were followed prospectively to evaluate the efficacy and safety of this therapy.. Of the 404 venous thromboembolism patients in the registry, 296 received rivaroxaban and had at least 3 months of follow-up. Of these, 118 (40%) had active malignancy (51% female, mean age 66 ± 10 years) and 178 had no cancer (47% female, mean age 55 ± 15 years). The 3 most common cancer locations were genitourinary (23.6%), gastrointestinal (20.3%), and lung (13.5%). There was no difference in venous thromboembolism recurrence between the malignant (3.3%) and the nonmalignant (2.8%) venous thromboembolism groups (P = .533). Borderline higher rates for major bleeding (P = .06) and nonmajor clinically relevant bleeding (P = .08) were observed in patients with cancer.. The "real world" effectiveness and safety of rivaroxaban is similar for venous thromboembolism patients with and without active malignancy.

Topics: Aged; Case-Control Studies; Comorbidity; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Patient Safety; Prospective Studies; Recurrence; Registries; Risk Assessment; Rivaroxaban; Venous Thromboembolism

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Humans; Morpholines; Postpartum Period; Rivaroxaban; Thiophenes; Venous Thromboembolism

Preventing venous thromboembolism (VTE) remains an important topic in the plastic surgery community. However, there is little consensus regarding appropriate VTE prophylaxis for patients undergoing common body contouring procedures.. This study compared the use of two novel oral anticoagulants (Rivaroxaban and Apixiban) vs low molecular weight heparin (LMWH) for postoperative chemical prophylaxis in body contouring plastic surgery procedures.. A single center retrospective chart review of 1572 patients who underwent body contouring plastic surgery procedures from January 2012 to February 2015 was performed. Major complications associated with chemical prophylaxis were reviewed including hematomas requiring surgical evacuation, acute blood loss anemia requiring transfusions, and thrombotic or hemorrhagic events.. Drug-related adverse events occurred in 1.27% (n = 20) of patients. The complications encountered by the 454 patients on LMWH consisted of 0.88% (n = 4) with hematomas requiring surgical evacuation, 0.44% (n = 2) with decreased hemoglobin requiring transfusions, and 0.22% (n = 1) with a deep vein thrombosis (DVT). The complications encountered by 703 patients on with Rivaroxaban consisted of 1.3% (n = 9) with hematomas requiring surgical evacuation, 0.43% (n = 3) with decreased hemoglobin requiring transfusions, and 0.1% (n = 1) with a DVT and pulmonary embolism. The complications encountered by 415 patients on with Apixaban consisted of 0.48% (n = 2) with a DVT.. Novel oral anticoagulants (Rivaroxaban and Apixiban) are comparable to LMWH for chemical prophylaxis after body contouring procedures with similar rates of drug-related complications. Further investigation is warranted with more clinical cases in order to recommend the use of this medication for routine postoperative chemical prophylaxis after body contouring procedures.. 3 Therapeutic.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Blood Loss, Surgical; Blood Transfusion; Factor Xa Inhibitors; Female; Hematoma; Heparin, Low-Molecular-Weight; Humans; Lipectomy; Male; Middle Aged; Postoperative Hemorrhage; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Texas; Treatment Outcome; Venous Thromboembolism; Young Adult

In this issue of Blood, Martinelli et al provide reassuring data that women taking oral anticoagulant therapy for venous thromboembolism (VTE) may use estrogen or progestin hormonal therapy to control the menstrual bleeding without increased risk for recurrent thromboembolism.

Topics: Anticoagulants; Enoxaparin; Estrogens; Female; Humans; Progestins; Rivaroxaban; Uterine Hemorrhage; Venous Thromboembolism

To describe the clinical use of rivaroxaban in the treatment of 4 dogs with vascular thrombosis, 2 with pulmonary thromboembolism and 2 with systemic thrombosis.. This report describes the use of a direct factor Xa anticoagulant newly approved in human patients for the treatment or prevention of arterial or venous thrombosis. The use of this medication in a clinical setting for canine patients with thromboembolism has not been described before. Two patients were treated with rivaroxaban for pulmonary thromboembolism. Decreases in thrombus size were seen in both patients, but one patient suffered acute respiratory distress and was euthanized while the other continued to do well at the time of this writing. The other 2 patients were treated for systemic thrombosis. Decreases in thrombus size were also noted. One patient later suffered hematochezia of unknown cause, and the other continued to do well at the time of this writing.. This is the first published report of the use of a new oral direct factor Xa anticoagulant in dogs in a clinical setting for the treatment of both pulmonary and systemic thrombosis. In this case series, we share our limited experience in the use of this new medication, our strategy in determining appropriate dosages, and our monitoring protocol.

Topics: Animals; Dog Diseases; Dogs; Factor Xa Inhibitors; Female; Male; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

The authors report a case of a 69-year-old woman who presented with a spontaneous spinal epidural hematoma (SSEH) 10 days after a total hip arthroplasty. The patient had been receiving 10 mg/d of rivaroxaban for 5 days for venous thromboembolism prophylaxis. She had a sudden onset of severe neck pain, followed by quadriplegia below C4. A dorsal SSEH was revealed by computed tomography. While preparing for the emergency evacuation of the SSEH, the neurological symptoms resolved spontaneously in 4 hours. The 1-month follow-up magnetic resonance imaging confirmed that the SSEH had completely resolved. The pathogenesis of SSEH is unclear, but anticoagulant therapy is a known risk factor. It is a relatively rare disorder. Only 1 case of SSEH has been reported, and that patient was receiving a nonsteroidal anti-inflammatory drug besides rivaroxaban, which is another known risk factor for bleeding disorders. [Orthopedics. 2016; 39(3):e558-e560.].

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Hematoma, Epidural, Spinal; Humans; Magnetic Resonance Imaging; Neck Pain; Rare Diseases; Risk Factors; Rivaroxaban; Tomography, X-Ray Computed; Venous Thromboembolism

Recent studies have demonstrated non-inferiority of rivaroxaban when compared to warfarin for the treatment of pulmonary embolism and deep venous thrombosis. Analysis of data from the EINSTEIN trials has demonstrated that patients who received rivaroxaban had a shorter length of stay (LOS) compared to those who received warfarin. However, these trials had strict inclusion and exclusion criteria, and were designed for a different primary outcome. Also, data from these closely monitored clinical trials may not reflect the daily practice of medicine.. To clarify this issue further, we performed a retrospective analysis at our institution, comparing the LOS between patients discharged on rivaroxaban and other conventional anticoagulants (warfarin, enoxaparin, and enoxaparin with warfarin).. This was a retrospective study of consecutive patients admitted to our institution from January 2011 to July 2014 with newly diagnosed venous thromboembolism (VTE). Inclusion criteria were age > 18 years and objective confirmation of VTE. Exclusion criteria included diagnosis of VTE 24 h after admission, contraindication to anticoagulation, treatment with fibrinolytic agents, patients already on anticoagulation, and pregnancy. Out of 1553 consecutive patients diagnosed with VTE, a total of 414 patients met the eligibility criteria. These patients were further subdivided into four groups based on their discharge anticoagulant: rivaroxaban, warfarin, enoxaparin, and warfarin with enoxaparin.. Patients discharged on rivaroxaban had a significantly shorter LOS compared with patients discharged on warfarin (3.5 vs. 7.0 days; p < 0.001), but not when compared to those discharged on enoxaparin alone (3.0 days) or enoxaparin with warfarin (4.0 days) (p > 0.05). The hospital incidence of bleeding and the 6-month readmission rates were not different among the different anticoagulants.. In patients admitted with newly diagnosed VTE, those discharged on rivaroxaban had a significantly shorter LOS compared to those discharged on warfarin. In the appropriate subset of patients with VTE, treatment with rivaroxaban may result in significant cost savings for the hospital.

Topics: Aged; Aged, 80 and over; Anticoagulants; Drug Therapy, Combination; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Length of Stay; Male; Middle Aged; Patient Discharge; Patient Readmission; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Compared with vitamin K antagonists, direct-acting oral anticoagulants (DOACs) have fixed dosing, limited drug interactions, and do not require therapeutic drug level monitoring. Dose adjustments are recommended for moderate renal dysfunction, low body weight, and select drug interactions.. The aim of our study is to determine if DOAC dose reductions were appropriate based on the manufacturer labeling recommendations for each agent. We also followed patients' treatment outcomes.. We retrospectively reviewed patients administered a DOAC at a reduced dose between January 2011 and August 2014. The primary outcome was adherence to current manufacturer dose recommendations. The secondary outcome measures were the incidence of thromboembolic events or any bleeding episodes, regardless of severity, while on therapy.. Of 224 patients included in the analysis, 43.3% of patients fit criteria for a dose adjustment according to manufacturer recommendations. Only 3 of 28 (10.7%) patients treated with apixaban met 2 out of 3 clinical criteria required for a dose reduction per manufacturer recommendations. Only 54.7% of rivaroxaban-treated patients and 32.2% of dabigatran-treated patients had renal insufficiency requiring a dose reduction. Half of our patient population received aspirin therapy, with 6.3% of patients on triple antithrombotic therapy (dual antiplatelet agents plus an anticoagulant). A past medical history significant for bleeding was prevalent in patients treated with a reduced-dose DOAC (32.1%, 20.4%, and 25.4% of patients in the apixaban-, rivaroxaban-, and dabigatran-treated groups, respectively). Thromboembolic events occurred in 10.7%, 3.6%, and 5.1% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively. Frequency of bleeding complications, regardless of severity, was 17.9%, 18.2%, and 23.7% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively.. We found that dose-adjusted DOAC therapy was often prescribed in a dose that was lower than package insert recommendations.

Topics: Aged; Aged, 80 and over; Antithrombins; Aspirin; Atrial Fibrillation; Comorbidity; Creatinine; Dabigatran; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Renal Insufficiency; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism

We investigated three-month clinical outcomes in patients with venous thromboembolism (VTE) treated with rivaroxaban or conventional anticoagulation in routine clinical practice. Between November 2012 and February 2015, 2,062 consecutive patients with VTE from 11 acute care hospitals in Switzerland were enrolled in the SWIss Venous ThromboEmbolism Registry (SWIVTER). Overall, 417 (20 %) patients were treated with rivaroxaban. In comparison to 1,645 patients on conventional anticoagulation, patients on rivaroxaban were younger (56 ± 18 vs. 65 ± 17 years; p<0.001), less often had pulmonary embolism (38 % vs 66 %; p<0.001), hypertension (26 % vs 41 %; p<0.001), cancer (10 % vs 28 %; p<0.001), congestive heart failure (10 % vs 17 %; p=0.001), diabetes (8 % vs 15 %; p<0.001), chronic lung disease (7 % vs 13 %; p=0.001), renal insufficiency (7 % vs 13 %; p=0.001), recent surgery (7 % vs 14 %; p<0.001), and acute coronary syndrome (1 % vs 4 %; p=0.009). VTE reperfusion therapy was more frequently used (28 % vs 9 %; p<0.001) and indefinite-duration anticoagulation treatment less often planned (26 % vs 39 %; p<0.001), respectively. In the propensity score-adjusted population, the risk of recurrent VTE was similar in patients on rivaroxaban vs conventional anticoagulation (1.2 % vs 2.1 %, hazard ratio [HR] 0.55, 95 % confidence interval [CI] 0.18-1.65; p=0.29); the risk of major bleeding was also similar, respectively (0.5 % vs 0.5 %, HR 1.00, 95 %CI 0.14-7.07; p=1.00). Conventional anticoagulation is still frequently used for the treatment of VTE, particularly in the elderly and those with comorbidities. Early clinical outcomes were comparable between propensity score-adjusted patient populations on rivaroxaban and conventional anticoagulation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Pulmonary Embolism; Registries; Retrospective Studies; Rivaroxaban; Switzerland; Thrombolytic Therapy; Treatment Outcome; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Humans; Rivaroxaban; Surgery, Plastic; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Humans; Rivaroxaban; Surgery, Plastic; Venous Thromboembolism

Compared with low-molecular-weight heparin (LMWH) and warfarin, the oral anticoagulant rivaroxaban has advantages, such as simplified care, that may lead to less health care resource utilization.. A retrospective, matched-cohort analysis was conducted using claims dated between January 2011 and December 2013 from the Truven Health Analytics MarketScan databases. Adult patients who had a primary diagnosis of deep vein thrombosis (DVT) during an outpatient or emergency room (ER) visit after November 2, 2012, and who were treated with rivaroxaban or LMWH/warfarin on the same day, were identified. Patients were observed over 1, 2, 3, and 4 weeks after the DVT diagnosis. The mean numbers of hospitalizations for all causes and for venous thromboembolism (VTE) (which included those for DVT or pulmonary embolism), as well as other health care resource utilization (ER, outpatient, and other visits), and the associated health care costs and pharmacy costs, were evaluated and compared between cohorts using the Lin method.. All of the 512 rivaroxaban-treated patients were well matched with the LMWH/warfarin-treated patients. The mean numbers of all-cause hospitalizations were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (0.012 vs 0.032; P = 0.044) and 2 weeks (0.022 vs 0.048; P = 0.040). The corresponding mean numbers of VTE-related hospitalizations were significantly lower with rivaroxaban over 1 week (0.008 vs 0.028; P = 0.020), 2 weeks (0.016 vs 0.042; P = 0.020), and 4 weeks (0.034 vs 0.068; P = 0.036). The mean numbers of all-cause and VTE-related outpatient visits were also significantly lower in rivaroxaban users compared with those in LMWH/warfarin users over 1, 2, 3, and 4 weeks (all, P < 0.001). In terms of all-cause and VTE-related ER and other visits, no statistically significant differences were found between cohorts over the first 4 weeks. The associated mean all-cause total health care costs were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (US $2332 vs $3428; P < 0.001) and 2 weeks ($3108 vs $4524; P < 0.001); moreover, significantly lower mean costs related to all-cause hospitalizations (weeks 1 and 2) and pharmacy (weeks 1-4) were observed in patients treated with rivaroxaban, while no differences were found in costs related to ER visits (weeks 1-4), outpatient visits (weeks 1-4), or other visits (with the exception of week 1).. Patients with DVT treated with rivaroxaban after an outpatient/ER visit had significantly lower mean numbers of hospitalizations and outpatient visits, as well as lower mean total, hospitalization, and pharmacy costs during the first 2 weeks of treatment compared with those in matched LMWH/warfarin users.

Topics: Adult; Aged; Anticoagulants; Databases, Factual; Female; Health Care Costs; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Outpatients; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis; Warfarin

Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban.. Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Complement Activation; Factor Xa; Factor Xa Inhibitors; Female; Humans; Inflammation; International Normalized Ratio; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Warfarin

Currently available anticoagulants have limitations for long-term treatment of venous thromboembolism (VTE). We have evaluated the efficacy and safety of direct oral anticoagulants (DOACs) for extended treatment of VTE. Four randomized controlled trials (RCTs) comparing DOACs (apixaban, rivaroxaban, and dabigatran) with placebo or warfarin for extended treatment of VTE were published. Primary efficacy outcome was recurrent VTE or VTE-related death, and primary safety outcome was major bleeding. DOACs significantly lower the risk of recurrent VTE or VTE-related death compared to placebo/warfarin, as well as all-cause mortality. Risk of major bleeding is not different with DOACs compared to placebo/warfarin. However, DOACs are associated with a significantly higher rate of the composite of major and clinically relevant bleeding compared to placebo. In conclusion, DOACs are effective and safe for the extended treatment of VTE, and may reduce the risk of all-cause mortality.

Topics: Administration, Oral; Anticoagulants; Aspirin; Dabigatran; Humans; Italy; Pyrazoles; Pyridones; Rivaroxaban; Time Factors; Venous Thromboembolism; Vitamin K; Warfarin

Introduction Venous thromboembolism (VTE) is a potentially fatal complication of hip arthroplasty and knee arthroplasty. The National Institute for Health and Care Excellence recommend rivaroxaban for VTE prevention. Amid concerns over bleeding complications, the modified thromboprophylaxis policy of Chelsea and Westminster Hospital (CWH; London, UK) advises enoxaparin given after surgery in the inpatient setting followed by rivaroxaban upon hospital discharge. This retrospective study investigated the efficacy and safety of rivaroxaban in this novel, modified venous-prophylaxis regimen in a surgical orthopaedic cohort at CWH. Methods A total of 479 patients who received modified thromboprophylaxis treatment at CWH after hip arthroplasty or knee arthroplasty between April 2013 and October 2014 formed the study cohort. Seven outcomes based on efficacy and safety while undergoing treatment with rivaroxaban were investigated: symptomatic deep-vein thrombosis (DVT), pulmonary embolism (PE), death, stroke, myocardial infarction (MI), major bleeding episodes (MBEs) and non-major bleeding episodes (NMBEs). Median follow-up was 369 days. Fisher's exact and Mann-Whitney U-tests were adopted to identify associations with these outcomes. Results Prevalence of symptomatic PE, DVT, death, stroke and MI during treatment was zero. One (0.2%) MBE and nine (1.9%) NMBEs occurred. The MBE (a wound haematoma) required a return to theatre for aspiration. Off-treatment VTEs occurred in four (0.8%) patients after completion of a course of rivaroxaban, and were associated with known risk factors. Conclusions Rivaroxaban is an effective and safe anticoagulant for thromboprophylaxis after hip arthroplasty or knee arthroplasty if used in a modified regimen involving enoxaparin administered in the inpatient setting followed by rivaroxaban upon hospital discharge.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Warfarin is the anticoagulant of choice for venous thromboembolism (VTE) treatment, although its suppression of the endogenous clot-dissolution complex APC:PS may ultimately lead to longer time-to-clot dissolution profiles, resulting in increased risk of re-thrombosis. This detrimental effect might not occur during VTE treatment using other anticoagulants, such as rivaroxaban or enoxaparin, given their different mechanisms of action within the coagulation network. A quantitative systems pharmacology model was developed describing the coagulation network to monitor clotting factor levels under warfarin, enoxaparin, and rivaroxaban treatment. The model allowed for estimation of all factor rate constants and production rates. Predictions of individual coagulation factor time courses under steady-state warfarin, enoxaparin, and rivaroxaban treatment reflected the suppression of protein C and protein S under warfarin compared to rivaroxaban and enoxaparin. The model may be used as a tool during clinical practice to predict effects of anticoagulants on individual clotting factor time courses and optimize antithrombotic therapy.

Topics: Adolescent; Adult; Aged; Anticoagulants; Blood Coagulation; Enoxaparin; Female; Humans; Male; Middle Aged; Models, Biological; Protein C; Protein S; Rivaroxaban; Venous Thromboembolism; Warfarin; Young Adult

Topics: Adult; Aged; Body Weight; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Life Change Events; Male; Middle Aged; Overweight; Recurrence; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Topics: Adolescent; Adult; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism; Young Adult

Observational data and results from post-hoc analyses in clinical trials suggest that direct oral factor Xa inhibitors might increase menstrual bleeding intensity in women of reproductive age, but the extent of this effect is unknown. We aimed to investigate the management and outcomes of vaginal bleeding complications during therapy with direct oral factor Xa inhibitors in a case series of women of reproductive age.. To identify individuals for inclusion in this case series, we searched two sources of prospectively collected data from women of reproductive age treated with direct oral factor Xa inhibitors: the non-interventional Dresden NOAC Registry (NCT01588119), which is based in the administrative district of Dresden (Saxony, Germany), and all locally archived data from phase 3 trials of direct oral factor Xa inhibitors done at University Hospital Carl Gustav Carus Dresden. Vaginal bleeding events were defined as any vaginal bleeding complications as reported by the patient. We collected data on type and dosage of anticoagulation; suspected or confirmed bleeding events, hospital admissions, and mortality; and pattern and management of vaginal bleeding events. For all cases of bleeding identified, we reviewed all available source data to identify examination results suggesting potential underlying anatomical causes of bleeding.. We identified 178 women of reproductive age who received direct oral factor Xa inhibitor therapy, of whom 57 had vaginal bleeding events, including 50 who received rivaroxaban, six who received apixaban, and one who received edoxaban. These 57 women had 72 vaginal bleeding events, including 59 cases of heavy menstrual bleeding and 13 bleeding events unrelated to the menstrual cycle. 51 (86%) of these heavy menstrual bleeding events (two major bleeding events, 17 clinically relevant non-major bleeding events, 32 minor bleeding events) were treated conservatively (eg, change of oral hormone therapy or reduction, temporary interruption, or discontinuation of direct oral factor Xa inhibitor) and the remaining eight (14%) events (three major bleeding events and five clinically relevant non-major bleeding events) required elective surgical or interventional treatment (hysterectomy, curettage, ovary excision, or excision of ovarian cysts). Of the 57 women, 13 (23%) had a second bleeding event and two (4%) had a third event. Nine patients had underlying anatomical abnormalities; compared with patients without abnormalities, these patients had more intense bleeding, more had recurrent bleeding (five [56%] of nine patients with abnormalities vs eight [17%] of 48 patients without abnormalities), and more needed surgical treatment for bleeding (eight [89%] of nine vs zero of 48).. Vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively, but patients with severe or recurrent vaginal bleeding complications should be assessed for underlying anatomical abnormalities, which might require surgical or interventional treatment. Further data are needed to provide guidance on prevention and treatment of vaginal bleeding complications in this patient population.. None.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hormone Replacement Therapy; Humans; Menorrhagia; Middle Aged; Progesterone; Prospective Studies; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Uterine Hemorrhage; Venous Thromboembolism

Contemporary rates of oral anticoagulant (OAC) therapy and associated outcomes among patients undergoing percutaneous coronary intervention (PCI) have been poorly described.. Using data from an integrated health care system from 2009 to 2014, we identified patients on OACs within 30 days of PCI. Outcomes included in-hospital bleeding and mortality. Of 9566 PCIs, 837 patients (8.8%) were on OACs, and of these, 7.9% used non-vitamin K antagonist agents. OAC use remained stable during the study (8.1% in 2009, 9.0% in 2014; P=0.11), whereas use of non-vitamin K antagonist agents in those on OACs increased (0% in 2009, 16% in 2014; P<0.01). Following PCI, OAC-treated patients had higher crude rates of major bleeding (11% versus 6.5%; P<0.01), access-site bleeding (2.3% versus 1.3%; P=0.017), and non-access-site bleeding (8.2% versus 5.2%; P<0.01) but similar crude rates of in-hospital stent thrombosis (0.4% versus 0.3%; P=0.85), myocardial infarction (2.5% versus 3.0%; P=0.40), and stroke (0.48% versus 0.52%; P=0.88). In addition, prior to adjustment, OAC-treated patients had longer hospitalizations (3.9±5.5 versus 2.8±4.6 days; P<0.01), more transfusions (7.2% versus 4.2%; P<0.01), and higher 90-day readmission rates (22.1% versus 13.1%; P<0.01). In adjusted models, OAC use was associated with increased risks of in-hospital bleeding (odds ratio 1.50; P<0.01), 90-day readmission (odds ratio 1.40; P<0.01), and long-term mortality (hazard ratio 1.36; P<0.01).. Chronic OAC therapy is frequent among contemporary patients undergoing PCI. After adjustment for potential confounders, OAC-treated patients experienced greater in-hospital bleeding, more readmissions, and decreased long-term survival following PCI. Efforts are needed to reduce the occurrence of adverse events in this population.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Anticoagulants; Atrial Fibrillation; Comorbidity; Dabigatran; Databases, Factual; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Length of Stay; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Patient Readmission; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stents; Stroke; Thrombosis; Venous Thromboembolism; Warfarin

Anticoagulants increase the risk of heavy menstrual bleeding (HMB). We sought to investigate the incidence, predictors and management of HMB in women on rivaroxaban compared to those on vitamin K antagonists (VKA). We addressed the issue as to whether HMB is associated with VTE recurrences. We performed a single-center prospective study in menstruating women aged 18-55years treated with rivaroxaban or VKA≥3months since the index VTE episode. Seventy six women on rivaroxaban and 45 patients on VKA were included. Patients on rivaroxaban more commonly reported HMB compared with those on VKA (31 [41%] vs. 8 [18%], p=0.009). Women treated with rivaroxaban more frequently needed interventions to reduce menstruation compared with those on VKA (29 [38%] vs. 6 [13%], p=0.004). During the median follow-up time of 13months, there were 8 (11%) recurrent VTE on rivaroxaban and 3 (7%) on VKA (p=0.5). Rivaroxaban treatment predisposed to HMB (odds ratio [OR] 3.2, 95% [confidence interval] CI 1.4-8.2, p=0.007) and the interruption of anticoagulant treatment for 2-3days (OR 3.2, 95% CI 1.1-11.6, p=0.033). HMB during the rivaroxaban treatment predisposed to recurrent VTE (OR 5.3, 95% CI 1.1-33.3, p=0.038). In menstruating women following VTE, rivaroxaban is associated with a two-fold higher risk of HMB compared with VKA. HMB predisposes to recurrent VTE episode, most likely due to the short interruptions of anticoagulation.

Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Middle Aged; Prospective Studies; Recurrence; Rivaroxaban; Uterine Hemorrhage; Venous Thromboembolism; Vitamin K; Young Adult

Topics: Adult; Anticoagulants; Enoxaparin; Hemorrhage; Humans; Morpholines; Rivaroxaban; Thiophenes; Thrombosis; Venous Thromboembolism

A prospective observational study was conducted in two clinical cohorts of patients to compare the effect of enoxaparin and rivaroxaban on rotational thromboelastometry (ROTEM), coagulation activation markers and thrombin generation.. A total of 188 consecutive patients scheduled for major orthopedic surgery receiving 40-mg enoxaparin subcutaneously or 10-mg rivaroxaban orally were evaluated. Blood samples were taken before induction of anesthesia and on day 4 after surgery [postoperative day 4 (pod 4)]. The extrinsically (EXTEM) and the intrinsically (INTEM) activated ROTEM assay, antithrombin, prothrombin fragments (F1 + 2), thrombin-antithrombin complex (TAT) and D-dimers were measured, and the thrombodynamic ratio (TDR) was calculated. Thrombin generation was determined using calibrated automated thrombography. To compare the groups, changes (Δ) in baseline versus pod 4 were calculated.. EXTEM clotting time (CT) increased more with rivaroxaban than with enoxaparin; values above the reference range were observed (median ΔEXTEM-CT 15 vs. 5 s, P ≤ 0.0001). The increase in INTEM-CT (values remained within the normal ranges) was slight with enoxaparin and significant with rivaroxaban; ΔINTEM-CT was comparable. EXTEM-TDR, unchanged with rivaroxaban, increased significantly with enoxaparin, whereas ΔINTEM-TDR was comparable. ΔAT, ΔF1 + 2 and ΔTAT were significantly lower in the rivaroxaban group. Endogenous thrombin potential (ETP), unchanged with rivaroxaban, decreased significantly with enoxaparin; the maximal rising slope (mean velocity rate index) decreased more with rivaroxaban.. Data show that prolonged CT in the extrinsic ROTEM and thrombin generation assays reflecting initiation and propagation of thrombin may be useful for detecting treatment with rivaroxaban. The significance of observed differences in markers of coagulation needs to be investigated further.

Topics: Aged; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Cohort Studies; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Orthopedic Procedures; Prospective Studies; Rivaroxaban; Thiophenes; Thrombelastography; Thrombin; Venous Thromboembolism

Rivaroxaban, a direct factor Xa inhibitor, affects laboratory clotting tests. We report here 10 venous thromboembolism patients with false-positive lupus anticoagulant during rivaroxaban therapy. Two dilute Russell Viper Venom time (dRVVT)-based integrated assays, HemosIL dRVVT Screen/HemosIL dRVVT Confirm (Instrumentation Laboratory, LA1/LA2 (Siemens, Germany) and LA1/LA2 (Siemens, Marburg, Germany), showed that the patients were lupus anticoagulant-positive. Antiphospholipid antibodies were negative except for one patient. Screening activated partial thromboplastin time-based assay PTT lupus anticoagulant was lupus anticoagulant-positive, whereas the confirmatory Staclot lupus anticoagulant (both Diagnostica Stago, France) was lupus anticoagulant-negative. Re-examination after discontinuation of rivaroxaban (>24 h) ruled out the presence of lupus anticoagulant. Our data indicate that to reliably evaluate lupus anticoagulant in patients on rivaroxaban, blood should be drawn 24 h after the last dose.

Topics: Antibodies, Antiphospholipid; Blood Coagulation Tests; Factor Xa Inhibitors; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Prothrombin Time; Rivaroxaban; Venous Thromboembolism

Rivaroxaban is non-inferior to warfarin for the treatment of venous thromboembolism, with regard to clinical efficacy and safety. The ex-vivo effects of warfarin versus therapeutic dose rivaroxaban on in-vivo markers of coagulation activation and thrombin generation remain undefined. The aim of this study was to compare the effects of warfarin and therapeutic dose rivaroxaban on ex-vivo thrombin generation (TG), and the in-vivo markers of coagulation activation, prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and D-dimer.. Eighty-five patients with venous thromboembolism were studied, 45 on warfarin, target INR 2.5 and 40 on rivaroxaban 20mg once daily.. Anticoagulation was in therapeutic range in 71% (32/45) warfarin and 65% (26/40) rivaroxaban treated patients. 8 patients on warfarin and 9 patients on rivaroxaban had subtherapeutic INR and rivaroxaban levels respectively. Both rivaroxaban and warfarin reduced endogenous thrombin potential (ETP) and peak thrombin, and prolonged lag time and time to peak, compared to normal controls (p<0.0001). The lag time and time to peak TG were longer, and peak thrombin was lower in patients receiving rivaroxaban (p<0.0001) compared with warfarin, although warfarin-treated patients had lower ETP (p=0.0008). In-vivo coagulation activation markers were within the normal ranges in all rivaroxaban-treated patients (including those with levels considered to be subtherapeutic) and in 37/45 warfarin-treated patients who had an INR≥2.0. The warfarin-treated patients with subtherapeutic INRs exhibited slightly raised F1.2 and/or TAT.. In conclusion, both rivaroxaban and warfarin provided effective anticoagulation, as assessed by inhibition of TG and makers of in-vivo coagulation activation.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

Venous thromboembolism (VTE) impacts ∼900,000 individuals annually in the US, causing up to 100,000 deaths. Patients experiencing VTE have heightened risk of recurrence. Initial parenteral anti-coagulation is standard therapy for acute VTE followed by ≥3 months of warfarin, which introduces the risk of major bleeding. Balancing increased risks of bleeding and recurrent VTE remains challenging. Recent clinical trials suggest that rivaroxaban, an oral direct inhibitor of factor Xa, provides an effective, safe, simplified approach to treatment. This study considers the economic implications of these data.. This study modeled inpatient, acute, and 1-year VTE costs for a hypothetical commercial plan with 1 million members. At baseline, all VTE patients receive standard therapy. Alternatively, 25% are instead treated with rivaroxaban. Model inputs are trial- and literature-based.. Standard therapy for VTE consumes 9474 inpatient days ($31.6 million). Added to that is treatment for 74 recurrences ($1.4 million); major and non-major bleed events ($1 million); and direct costs of anti-coagulation ($5.3 million). Alternatively, a 25% shift to oral anti-coagulation with rivaroxaban reduces inpatient days (by 5%); associated acute-care costs (by 2%); recurrences and costs (by 6%). Four major bleeding events are prevented, at the cost of one additional non-major bleeding event, which, taken together, reduce net utilization by 9%. Direct costs of anti-coagulation increase by 5%.. The reduction in inpatient utilization, recurrences, and major bleeding resulting from a 25% shift from standard therapy to rivaroxaban following acute VTE would conserve ∼$860,475 for every 1 million commercial health plan enrollees.

Topics: Anticoagulants; Computer Simulation; Cost-Benefit Analysis; Drug Therapy, Combination; Enoxaparin; Hemorrhage; Hospitalization; Humans; Models, Econometric; Pulmonary Embolism; Recurrence; Rivaroxaban; United States; Venous Thromboembolism; Vitamin K

Medical costs that may be avoided when any of the four new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF) were estimated and compared. Additionally, the overall differences in medical costs were estimated for NVAF and venous thromboembolism (VTE) patient populations combined.. Medical cost differences associated with NOAC use vs warfarin or placebo among NVAF and VTE patients were estimated based on clinical event rates obtained from the published trial data. The clinical event rates were calculated as the percentage of patients with each of the clinical events during the trial periods. Univariate and multivariate sensitivity analyses were conducted for the medical-cost differences determined for NVAF patients. A hypothetical health plan population of 1 million members was used to estimate and compare the combined medical-cost differences of the NVAF and VTE populations and were projected in the years 2015-2018.. In a year, the medical-cost differences associated with NOAC use instead of warfarin were estimated at -$204, -$140, -$495, and -$340 per patient for dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, among the hypothetical population, the medical-cost differences were -$3.7, -$4.2, -$11.5, and -$6.6 million for NVAF and acute VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, for the combined NVAF, acute VTE, and extended VTE patient populations, medical-cost differences were -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban, respectively. Medical-cost differences associated with use of NOACs were projected to steadily increase from 2014 to 2018.. Medical costs are reduced when NOACs are used instead of warfarin/placebo for the treatment of NVAF or VTE, with apixaban being associated with the greatest reduction in medical costs.

Topics: Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Costs and Cost Analysis; Dabigatran; Health Expenditures; Hemorrhage; Humans; Models, Econometric; Myocardial Infarction; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; United States; Venous Thromboembolism; 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

The oral Factor Xa inhibitor rivaroxaban (Xarelto) has been the pharmacologic agent used for venous thromboembolism (VTE) prophylaxis after primary hip and knee arthroplasty (THA/TKA) at our institution since February 2012. The purpose of our study was to compare rates of VTE and major bleeding between rivaroxaban and our previous protocol of enoxaparin after THA/TKA. A retrospective cohort study was performed including 2406 consecutive patients at our institution between 1/1/11 and 9/30/13. Patients who did not have unilateral primary THA/TKA or who received other anticoagulants were excluded. Of the 1762 patients included, 1113 patients (63.2%) received enoxaparin and 649 patients (36.8%) received rivaroxaban. This study found no demonstrable differences between these two anticoagulants in rates of VTE, infection, reoperation, transfusion, or major bleeding. Therapeutic, Retrospective comparative study, Level III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Patients with cancer account for 20 % of cases of venous thromboembolism (VTE). Cancer patients are at increased risk for VTE during the entire course of their disease, also in absence of traditional VTE risk factors. Furthermore, patients with VTE and cancer have an estimated risk of bleeding of 15-20 % per year while on anticoagulant treatment. For these reasons, treatment of acute VTE in patients with cancer remains a clinical challenge. In clinical studies, which included about 27,000 patients, new oral anticoagulants (NOACs) have been shown to be as effective and safe as conventional anticoagulation (heparin given with and followed by vitamin K antagonists) for the treatment of VTE. In these studies, 1227 patients with active cancer were enrolled. Preliminary results of subgroup analyses and meta-analyses of randomized clinical trials suggest that NOACs could represent an alternative to conventional anticoagulation in patients with active cancer. Further "ad hoc" studies evaluating the clinical benefit of treatment with NOACs in patients with VTE and cancer are needed.

Topics: Anticoagulants; Dabigatran; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism

Determination of plasma rivaroxaban concentration may be necessary in certain clinical situations. Rivaroxaban concentration can be accurately and rapidly determined using a chromogenic anti-activated factor X (factor Xa) assay with specific drug calibrator material. However, there are currently no Food and Drug Administration (FDA)-approved rivaroxaban calibrators available in the United States.. To determine whether FDA-approved commercial kits for measuring heparin anti-factor Xa activity can be used to assess rivaroxaban concentrations when calibrated for unfractionated heparin or low-molecular-weight heparins.. Trough and peak samples were taken from 30 patients taking rivaroxaban as part of their routine care for atrial fibrillation or venous thromboembolism. The samples were tested using 3 different FDA-approved commercial kits for measuring heparin anti-factor Xa activity.. There was acceptable correlation between rivaroxaban levels and heparin anti-factor Xa activity using Berichrom and COAMATIC heparin kits. The STA liquid heparin method was the most sensitive to presence of rivaroxaban.. This study demonstrates a strong correlation, but variability between kits, for assessing rivaroxaban concentrations using heparin anti-factor Xa assays. The extent of the heparin calibration curve significantly limits the measurable rivaroxaban range, and this application may be useful only for trough samples. The STA liquid heparin, being exquisitely sensitive to rivaroxaban, may be suitable for ruling out presence of the drug. The routine use of heparin-calibrated anti-factor Xa assays to quantify rivaroxaban is not advocated, and when applied, it must be used with caution and limitations clearly understood.

Topics: Atrial Fibrillation; Calibration; Chromogenic Compounds; Factor Xa; Factor Xa Inhibitors; Female; Heparin; Humans; Male; Middle Aged; Reagent Kits, Diagnostic; Rivaroxaban; United States; Venous Thromboembolism

Rivaroxaban is increasingly used to treat patients with acute venous thromboembolism (VTE), a potentially life-threatening condition. Because absorption of rivaroxaban decreases from nearly 100% to 66% under fasting conditions, it is recommended that VTE patients take rivaroxaban with a meal. However, this recommendation is based on preclinical pharmacokinetic (PK) studies in healthy volunteers. So far, no clinical evidence is available to support this recommendation. We describe a case of a compliant young patient who developed recurrent pulmonary embolism during rivaroxaban treatment. PK studies provided evidence that malabsorption of rivaroxaban 20 mg due to irregular intake of meals during shift work was the leading cause of recurrent pulmonary embolism. When the patient was instructed to take rivaroxaban with a regular meal, peak plasma concentrations increased from 115 to 318 ng mL(-1) (+ 176%). Consequently, the importance of taking rivaroxaban with food may have a greater clinical relevance than data from preclinical PK studies suggest.

Topics: Adult; Blood Coagulation Tests; Drug Monitoring; Factor Xa Inhibitors; Food-Drug Interactions; Humans; Job Description; Male; Meals; Medication Adherence; Personnel Staffing and Scheduling; Predictive Value of Tests; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Adolescent; Adult; Aged; Anticoagulants; Antiphospholipid Syndrome; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Rivaroxaban; Venous Thromboembolism; Vitamin K; Young Adult

The clinical introduction of new oral anticoagulants (NOACs) has stimulated the development of tests to quantify the effects of these drugs and manage complications associated with their use. Until recently, the only treatment choices for the prevention of venous thromboembolism in orthopedic surgical patients, as well as for stroke and systemic embolism in patients with atrial fibrillation, were vitamin K antagonists, antiplatelet drugs, and unfractionated and low-molecular-weight heparins. With the approval of NOACs, treatment options and consequent diagnostic challenges have expanded.. To study the utility of thromboelastography (TEG) in monitoring and differentiating between 2 currently approved classes of NOACs, direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban).. Blood samples from healthy volunteers were spiked with each NOAC in both the presence and absence of ecarin, and the effects on TEG were evaluated.. Both the kaolin test reaction time (R time) and the time to maximum rate of thrombus generation were prolonged versus control samples and demonstrated a dose response for apixaban (R time within the normal range) and dabigatran. The RapidTEG activated clotting time test allowed the creation of a dose-response curve for all 3 NOACs. In the presence of anti-Xa inhibitors, the ecarin test promoted significant shortening of kaolin R times to the hypercoagulable range, while in the presence of the direct thrombin inhibitor only small and dose-proportional R time shortening was observed.. The RapidTEG activated clotting time test and the kaolin test appear to be capable of detecting and monitoring NOACs. The ecarin test may be used to differentiate between Xa inhibitors and direct thrombin inhibitors. Therefore, TEG may be a valuable tool to investigate hemostasis and the effectiveness of reversal strategies for patients receiving NOACs.

Topics: Adolescent; Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Thrombelastography; Venous Thromboembolism; Young Adult

Topics: Adult; Aged; Chemical and Drug Induced Liver Injury; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Prospective Studies; Registries; Rivaroxaban; Venous Thromboembolism

For over 50 years, warfarin was the only oral anticoagulant approved in the United States. In 2011, the Food and Drug Administration (FDA) approved rivaroxaban. Since its introduction, rivaroxaban has served as an alternative to warfarin to minimize drug interactions and avoid drug monitoring. The objective of this study was to evaluate the appropriateness of rivaroxaban dosing, indication and safety in a community hospital and to identify areas for improvement in its use.. This single-centre, retrospective review evaluated patients who received at least one dose of rivaroxaban between November 2011 and July 2013. The primary outcome included appropriateness of the first day of therapy based on indication and renal function per FDA-approved dosing recommendations for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) and for the treatment or prevention of venous thromboembolism (VTE). The secondary outcome included incidence of major bleeding or non-major clinically relevant bleeding.. Of the 445 patients evaluated, 36·9% of patients treated for NVAF and 12·4% treated for VTE were on an inappropriate regimen. Major bleeding within 12 months occurred in 3·5% of patients treated for NVAF, 1·2% for VTE and 0% for off-label indications with a similar trend for non-major clinically relevant bleeding (3·8%, 1·8% and 0%, respectively).. Though offering potential advantages over warfarin, the use of rivaroxaban should be monitored to increase appropriateness of therapy and improve patient safety. Therapeutic interchanges, pharmacist-directed interventions and other initiatives can be implemented to ensure appropriate use.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Dose-Response Relationship, Drug; Embolism; Factor Xa Inhibitors; Female; Hemorrhage; Hospitals, Community; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Venous Thromboembolism

Topics: Aged; Arthroplasty, Replacement, Knee; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Patient Selection; Risk Assessment; Risk Factors; Rivaroxaban; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thromboembolism

Although data from the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1-4 trials have shown a similar postoperative bleeding risk between rivaroxban and enoxaparin in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), anecdotal observations from local institutions have suggested that postoperative bleeding rates seemed higher in patients who received rivaroxaban than those reported in the RECORD trials. Thus, the objective of this pilot study was to assess postoperative bleeding events observed in clinical practice in patients receiving rivaroxaban after undergoing THA and TKA and to compare their results with those published in the RECORD trials.. Retrospective cohort study with a comparator group of patients from the RECORD 1-4 trials.. Two institutions within a regional health care system.. Four hundred forty adults who received at least one dose of rivaroxaban 10 mg daily after undergoing THA or TKA in the two institutions between August 2011 and October 2013 (cohort group), and 6183 patients who received rivaroxaban in the RECORD 1-4 trials (comparator group).. Postoperative bleeding was assessed in the cohort patients versus the patients in the RECORD trials. The primary outcome, occurrence of any postoperative bleeding, was a composite of major and clinically relevant nonmajor bleeding as defined in the RECORD trials. Any postoperative bleeding occurred in 6.8% of the cohort patients versus 3.2% of the RECORD trial patients (p<0.0001); 1.4% of the cohort patients versus 0.38% of the RECORD trial patients suffered a major bleed (p=0.013). Within defined major bleeding, bleeding leading to reoperation and clinically overt extrasurgical site bleeding resulting in either a hemoglobin level decrease of at least 2 g/dl or transfusion of 2 units or greater of packed red blood cells were reported in 0.68% versus 0.19% (p=0.073) and 0.68% versus 0.13% (p=0.032), respectively, of the cohort patients versus the RECORD trial patients.. Overall, any postoperative bleeding in the cohort patients occurred significantly more frequently than that observed in the RECORD trial patients. The major bleeding rate was also significantly higher in the cohort patients, influenced by higher rates of bleeding leading to reoperation and clinically overt extrasurgical site bleeding resulting in either a hemoglobin decrease of at least 2 g/dl or transfusion of two units or greater of packed red blood cells. These findings from our pilot study are thought provoking and, thus, invite further investigation.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials as Topic; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Until recently, warfarin has been the primary treatment of venous thromboembolism (VTE). Limited data are available regarding physician attitudes toward anticoagulant choice in the setting of novel oral anticoagulant (NOAC) availability. This study sought to evaluate attending physician attitudes toward NOACs. A survey was sent to attending physicians from internal medicine (primary care and hospitalist medicine), family medicine, cardiology, and hematology-oncology asking about their preference and reasoning for choice of oral anticoagulant for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Warfarin was the most common choice of initial treatment of both DVT (85.6%) and PE (89%). Among the specialties surveyed, cardiologists were more likely to use rivaroxaban as initial treatment of VTE as compared to other specialties including internal medicine or hematology (p=0.011 for DVT and 0.004 for PE). Cost-effectiveness and lack of a reversal agent were cited as the major disadvantages for NOAC use.

Topics: Administration, Oral; Anticoagulants; Cardiology; Cost-Benefit Analysis; Cross-Sectional Studies; Dabigatran; Health Care Surveys; Hematology; Humans; Internal Medicine; Practice Patterns, Physicians'; Primary Health Care; Rhode Island; Rivaroxaban; Specialization; Venous Thromboembolism; Warfarin

Four direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation.. We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014.. Overall, visits with anticoagulation use increased from 2.05 (95% confidence interval [CI], 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits (P < .001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P < .001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 (P < .001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%).. Direct oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation.

Topics: Administration, Oral; Adult; Age Factors; Aged; Ambulatory Care; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Pyrazoles; Pyridones; Rivaroxaban; United States; Venous Thromboembolism; Warfarin; Young Adult

Topics: Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Patient Admission; Pilot Projects; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Deep-vein thrombosis and subsequent pulmonary embolism are major complications in total joint arthroplasty of the lower limbs. New oral anticoagulants are increasingly prescribed as thromboprophylaxis due to their simple administration and encouraging phase III marketing studies.. In this observational study, we compared the efficacy and safety of rivaroxaban with nadroparin in 1302 unselected patients receiving hip or knee arthroplasty.. Venous thrombembolism occurred in 3.3% (2.3%; 4.7%, 95% CI, n = 838) of patients receiving rivaroxaban and in 4.3% (2.7%; 6.7%, 95% CI, n = 464) of patients receiving nadroparin resulting in an absolute risk reduction (ARR) of 1.0% (-1.4%; 3.3%, 95% CI).. With an odds ratio of 0.6 (0.4; 1.0, 95% CI), rivaroxaban was associated with a decreased perioperative drop in haemoglobin exhibiting an improved thromboprophylactic profile when compared to high dose nadroparin. Furthermore, transfusion rates were 8.8% (-2.7%; 19.9%, 95% CI) lower in patients receiving rivaroxaban. However, as previous studies have shown, low preoperative haemoglobin remains the most predictive factor for postoperative transfusions (OR: 2.4 [1.3; 4.4, 95% CI]).

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Causality; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Germany; Humans; Male; Middle Aged; Nadroparin; Postoperative Complications; Prevalence; Risk Factors; Rivaroxaban; Survival Rate; Treatment Outcome; Venous Thromboembolism

Stroke and venous thromboembolism (VTE) affect millions of patients. The vitamin K antagonist, warfarin, has been the main oral anticoagulant used to treat these conditions despite many limitations associated with its use. Recently, multiple novel oral anticoagulants have been approved and are reshaping how patients with atrial fibrillation (AF) at risk of stroke and patients with VTE are treated. The direct thrombin inhibitor, dabigatran etexilate , is among these novel agents that have been developed to overcome limitations with warfarin.. In this article, authors describe the pharmacokinetic and pharmacodynamic properties of dabigatran etexilate and summarize the clinical evidence and controversy surrounding its use in the US, Canada and Europe.. Dabigatran has demonstrated similar efficacy and safety to enoxaparin for VTE prevention in patients undergoing hip and knee arthroplasty, and to warfarin for the treatment of VTE. Dabigatran (110 mg) is noninferior and dabigatran (150 mg) is superior to warfarin for stroke prevention in patients with nonvalvular AF, with a lower rate of intracranial hemorrhage reported at both doses. Apixaban, rivaroxaban and edoxaban provide alternate anticoagulant options to dabigatran. While there are many similarities, there are also significant differences to consider in agent selection based on patient-specific characteristics.

Topics: Antithrombins; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Cardiovascular Diseases; Clinical Trials as Topic; Dabigatran; Enoxaparin; Humans; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism

Rivaroxaban is a convenient oral anticoagulant for patients with venous thromboembolism (VTE). The impact of rivaroxaban and vitamin K antagonists (VKAs) on abnormal uterine bleeding (AUB) in real life has not been previously explored.. We performed a single-center retrospective study on AUB in female VTE patients of reproductive age who were treated with either rivaroxaban or VKAs.. Questionnaire results were available for 52 patients in each treatment group. Approximately two thirds of all women reported AUB after initiation of anticoagulant therapy. Patients using rivaroxaban were more likely to experience prolonged (>8days) menstrual bleeding (27 % vs. 8.3%, P=0.017). Rivaroxaban treatment increased the duration of menstrual bleeding from median 5 (IQR 3.5-6.0) days before start of treatment to 6 (IQR 4.1-8.9) days (P<0.001). VKA treatment did not lead to significant prolongation of the menstrual period. Patients on rivaroxaban more frequently reported an unscheduled contact with a physician for AUB than women using VKAs (41% vs. 25%, P=0.096). They also reported increased need for menorrhagia-related medical or surgical intervention (25% vs. 7.7%, P=0.032) and had more adaptations of anticoagulant therapy (15% vs. 1.9%, P=0.031).. AUB is frequent after initiation of anticoagulant therapy for acute symptomatic VTE. Compared to VKAs, rivaroxaban was associated with prolonged menstrual bleeding and more medical interventions and adaptation of anticoagulant treatment for AUB. These data can guide proactive discussion with patients starting anticoagulant therapy.

Topics: Adult; Anticoagulants; Female; Humans; Retrospective Studies; Risk Factors; Rivaroxaban; Uterine Hemorrhage; Venous Thromboembolism; Vitamin K; Young Adult

According to guidelines, initiation of pharmacological thromboprophylaxis after total knee or hip replacement is recommended and associated with improved patient outcomes. However, data on how these recommendations are followed in clinical practice are sparse.. All patients undergoing first-time total knee or hip replacement in Denmark 2008-2011 were identified. By cross-referencing Danish nationwide registries, quantitative use of anticoagulants administered orally and subcutaneously post-discharge was assessed by number of claimed prescriptions after surgery. Logistic regression analysis was used to identify factors associated with initiation of prophylaxis.. A total of 50,389 patients were included in the study (median age 69, inter-quartile range 62-76). Novel oral anticoagulants were initiated in 14.7 % of the patients and heparins/fondaparinux in 2.3 % of the patients. The use of anticoagulants increased from 6.3 % in 2008 to 30.0 % of patients in 2011. Among patients initiating prophylaxis with a novel oral anticoagulant post-discharge, almost all were treated according to guidelines in terms of treatment duration. Factors significantly associated with an increased chance of prophylaxis among total hip replacement patients were: age (per 10-year increments) and female gender.. Use of pharmacological thromboprophylaxis after total knee or hip replacement was low, but increasing during the study period. This is probably due to increased availability of novel oral anticoagulants. Further initiatives to increase guideline recommended use of prophylactic anticoagulation after orthopaedic surgery are warranted.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dabigatran; Denmark; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Postoperative Complications; Quality Improvement; Registries; Retrospective Studies; Risk Assessment; Rivaroxaban; Statistics, Nonparametric; Survival Rate; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism (VTE) is increasingly diagnosed in pediatric patients, and anticoagulant use in this population has become common, despite the absence of US Food and Drug Administration (FDA) approval for this indication. Guidelines for the use of anticoagulants in pediatrics are largely extrapolated from large randomized controlled trials (RCTs) in adults, smaller dose-finding and observational studies in children, and expert opinion. The recently FDA-approved direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban, provide potential advantages over oral vitamin K antagonists and subcutaneous low-molecular-weight heparins (LMWHs). However, key questions arise regarding their potential off-label clinical application in pediatric thromboembolic disease. In this Perspective, we provide background on the use of LMWHs such as enoxaparin as the mainstay of treatment of pediatric provoked VTE; identify key questions and challenges with regard to DOAC trials and future DOAC therapy in pediatric VTE; and discuss applicable lessons learned from the recent pilot/feasibility phase of a large multicenter RCT of anticoagulant duration in pediatric VTE. The challenges and lessons learned present opportunities to improve evidence for anticoagulant therapies in pediatric VTE through future clinical trials.

Topics: Adult; Age Factors; Anticoagulants; Child; Child, Preschool; Clinical Trials as Topic; Dabigatran; Disease Management; Evidence-Based Medicine; Heparin, Low-Molecular-Weight; Humans; Infant; Multicenter Studies as Topic; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism

Venous thromboembolism (VTE) is one of the severe complications of total hip arthroplasty (THA) and total knee arthroplasty (TKA). The incidence of VTE could be reduced if preventive antithrombotic medicines are used; however, the incidence of bleeding may increase. Rivaroxaban is a factor Xa inhibitor that prevents VTE after THA or TKA. This study is designed to confirm the efficacy and safety of rivaroxaban in Taiwan. This is a retrospective database study based on the data of 6996 patients provided by the Taiwan National Health Insurance Research Database from 2008 to 2012. The data included the number of prescription, the cost of prescription, and case number for patients treated with antithrombotic agents for the prevention or treatment of joint arthroplasty complications (including THA, TKA, partial hip arthroplasty, revision THA and TKA), and the incidence of thrombosis and hemorrhage from year 2008 to 2012. The overall postoperative VTE rate was 0.49%. Compared with other antithrombotic drugs, rivaroxaban and heparin analogs can reduce the percentage of thrombosis. We also found that the expenditure and hospitalization was less in the rivaroxaban group than in the heparin analogs group. Because some benefits of rivaroxaban were found in our study, further cost-effective and drug safety studies are warranted. It is important to consider the cost-effective principle for the use of antithrombotic drugs in preventing thromboembolic complications after total joint arthroplasty.

Topics: Arthroplasty, Replacement, Knee; Health Expenditures; Hospitalization; Humans; Patient Discharge; Rivaroxaban; Taiwan; Venous Thromboembolism

Rivaroxaban, a selective inhibitor of active factor X, is metabolized by cytochrom P450 3A4 (CYP3A4) and is a substrate for transporter protein--P-glycoprotein (P-gp). Amiodarone, an antiarrhytmic agent, is classified as moderate CYP3A4 and P-gp inhibitor.. A 75-year-old male, who underwent lobectomy for bronchiectasis many years ago, is presented. For one year the patient was treated with rivaroxaban (20 mg/d) due to venous thromboembolism and recurrent episodes of atrial fibrillation. Two weeks after amiodarone initiation (200 mg/d) hemoptysis occurred and computed tomography revealed unilateral pulmonary infiltrates with ground-glass opacities limited to the lower lobe of the left lung. The symptoms disappeared following discontinuation of the two medications and did not recur while rivaroxaban was reintroduced in a dose of 15 mg/d; measurement of anti-Xa activity confirmed it as a therapeutic dose. Amiodarone, that had been used for a short time and well tolerated a few years before, was definitely withdrawn.. The authors suggest, that the concomitant use of rivaroxaban and amiodarone should be very careful in patients with a history of pulmonary disease.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Bronchiectasis; Drug Therapy, Combination; Factor Xa Inhibitors; Hemoptysis; Humans; Male; Radiography; Rivaroxaban; Venous Thromboembolism

We herein report a case presenting with cerebral venous sinus thrombosis (CVST) associated with primary antiphospholipid syndrome (APS). The patient developed recurrent CVST followed by a hemorrhagic ischemic stroke despite the use of warfarin during the appropriate therapeutic window. Thus, we substituted warfarin to rivaroxaban with prednisolone and obtained a good clinical course. In addition to the effect of prednisolone of inhibiting elevated lupus anticoagulants and the recurrence of arterial thrombosis, rivaroxaban may prevent CVST and inhibit hypercoagulability induced by corticosteroids. The combination of an anti-Xa inhibitor and corticosteroid may be an alternative treatment for CVST and arterial thrombus with warfarin-resistant APS.

Topics: Adrenal Cortex Hormones; Anticoagulants; Antiphospholipid Syndrome; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Male; Middle Aged; Rivaroxaban; Stroke; Thrombosis; Venous Thromboembolism; Warfarin

To compare the efficacy and safety of 3 rivaroxaban regimen in patients with venous thromboembolism (VTE).. This is a retrospective study. Thirty three inpatients with VTE received rivaroxaban were divided into 3 groups, in which 16 patients were treated with 15 mg rivaroxaban twice daily for 21 days then followed by 20 mg once per day till 3 months (group 1), 9 patients were treated with 20 mg rivaroxaban once daily for 3 months (group 2), 8 patients were treated with 10 mg rivaroxaban once daily for 3 months. The reduction rate of D-Dimer on the third therapy day, the duration of D-Dimer normalization and hospital stay as well as symptom remission, the imaging assessment results after three months treatment, rate of recurrent VTE, bleeding, liver and kidney function were compared among the 3 groups.. The reduction rates of D-Dimer on the third therapy day were significantly higher ((46.12 ± 15.42) % vs. (26.59 ± 8.11) % and (25.55 ± 14.00) %, P = 0.02, P = 0.01), and the duration of D-Dimer normalization was significantly shorter ((17.9 ± 7.7) days vs. (24.1 ± 5.1) days and (26.3 ± 6.2) d, P = 0.03, P < 0.01) in group 1 than in group 2 and 3. There was one recurrent deep-vein thrombosis in group 3, one non-major bleeding in group 1 and group 3. Major bleeding or liver and kidney dysfunction were not observed in these patients.. Venous thromboembolism can be safely and effectively treated by rivaroxaban, and does of 15 mg twice daily for 21 days followed by 20 mg once daily for 3 months are superior to the other 2 tested therapy regimen in this patient cohort.

Topics: Fibrin Fibrinogen Degradation Products; Hemorrhage; Humans; Length of Stay; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arthroscopy; Blood Loss, Surgical; Dabigatran; Factor VIII; Hemophilia A; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Single-Domain Antibodies; Venous Thromboembolism

To evaluate the efficacy and safety of three antithrombotic agents on venous thromboembolism (VTE) after unilateral total knee arthroplasty.. From November 2011 to March 2014, 149 patients undergoing unilateral total knee arthroplasty for knee osteoarthritis were reviewed. Among them, there were 66 males and 83 females, ranging in age from 48 to 76 years old. All the cases were randomly divided into three groups including Aspirin group, low-molecular-weight heparin (LMWH) group, and rivaroxaban group, according to antithrombotic agents. Deep vein thrombosis (DVT), pulmonary embolism (PE) and bleeding complication (including wound ecchymosis, hematoma and other local complications, gastrointestinal, cardiovascular, urinary hemorrhage and other major bleeding events) of antithrombotic agents were observed and analyzed statistically at the 6 week, 8 week, and 12 week after operation.. Among patients who received Aspirin (48 cases), 4 patients had DVT, in 1 patient had PE, and 2 patients had bleeding complication. Among 54 patients in low-molecular-weight heparin group, 3 patients had DVT, 1 patient had PE, and 3 patients had bleeding complication. While among those patients received the rivaroxaban (47 cases), 3 patients had DVT, 0 patient had PE, and 11 patients had bleeding complication. There were no statistically differences among three groups on DVT, and PE (P>0.05). The incidence of bleeding complication in rivaroxaban group was higher than the other two antithrombotic agents, and the difference among the three groups was statistically significant (P<0.05).. Aspirin, low-molecular-weight heparin, and rivaroxaban could effectively reduce the incidence of VTE after total knee arthroplasty, and their efficacy was similar. Rivaroxaban has a higher incidence of bleeding complication and further clinical trials are required to be conducted to assess the safety of rivaroxaban in clinical.

Topics: Aged; Arthroplasty, Replacement, Knee; Aspirin; Case-Control Studies; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

Topics: Acute Disease; Anticoagulants; Benzimidazoles; Dabigatran; Drug Approval; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism

The prevalence of venous thromboembolism (VTE) has been increasing in China. However, the treatment pattern and economic burden of these patients have not been well-understood.. The objective of this study was to examine the patient characteristics, treatment pattern, anticoagulant monitoring, and economic burden of VTE among hospitalized patients in China.. Hospitalizations with a diagnosis of VTE [including deep vein thrombosis (DVT) or pulmonary embolism (PE)] between 1 January 2010 and 30 June 2013 were included. Descriptive analysis was conducted for patients' characteristics, anticoagulant treatment, international normalized ratio (INR) monitoring, and hospitalization cost [in 2013 Chinese yuan (Y) and US dollars (US$)]. Multivariate regressions were performed to assess factors associated with oral anticoagulant use and total costs of inpatient care.. A total of 1,047 VTE-related hospitalizations were selected. The sample had a mean age of 62.4 years, with 45.9 % female. About 46.3 % of hospitalizations used heparin only, 35.0 % used warfarin, 0.8 % used rivaroxaban, and 18.0 % did not use anticoagulants. Among hospitalizations where warfarin was used, 90.8 % received at least one INR test and only 30 % had the last INR within the target therapeutic range (2-3) before discharge. The mean (standard deviation) total cost per hospitalization was Y29,114 (43,772) [US$4,757 (7,152)]. PE, VTE as primary diagnosis, female, insurance coverage, anticoagulant treatment, co-morbidities, admission condition, and surgical procedure were significantly associated with inpatient costs.. Conventional anticoagulants were most commonly used in the study sample. Under-monitoring and suboptimal care may be an issue for patients treated with warfarin. The average total inpatient cost of VTE-related hospitalizations is high.

Topics: Anticoagulants; China; Female; Health Care Costs; Heparin, Low-Molecular-Weight; Hospitalization; Humans; International Normalized Ratio; Logistic Models; Male; Middle Aged; Morpholines; Pulmonary Embolism; Retrospective Studies; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

Extended duration anticoagulation with rivaroxaban for an additional 6-12 months can reduce recurrent venous thromboembolic events (VTE) compared to placebo by ~82%, but at the detriment of increased bleeding. We sought to estimate the cost-effectiveness of extended duration prophylaxis of recurrent VTE with rivaroxaban.. A Markov model was developed to estimate the cost-effectiveness of extended duration rivaroxaban, 20mg daily, compared to placebo using a Medicare perspective, a one-monthcycle length and a 40-year time horizon. The model assumed a cohort of 58-year-old patients who had already completed an initial 6-12 months of anticoagulation with rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical equipoise with respect to the need for continued anticoagulation. Data sources included EINSTEIN-Extension and other published studies of VTE. Outcomes included direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).. Extended duration rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of bleeding and recurrent VTE, the hazard ratio of developing a recurrent event while on rivaroxaban and time horizon. Monte Carlo Simulation suggested rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a willingness-to-pay threshold of $50,000/QALY.. Despite the cost of rivaroxaban and an increased risk of bleeding, extending VTE treatment for an additional 6-12 months with rivaroxaban was found cost-effective compared to the placebo over a 40-year time horizon.

Topics: Anticoagulants; Cohort Studies; Cost-Benefit Analysis; Female; Humans; Male; Markov Chains; Middle Aged; Models, Economic; Morpholines; Rivaroxaban; Thiophenes; United States; Venous Thromboembolism

Topics: Adult; Anticoagulants; Female; Humans; Necrosis; Rivaroxaban; Skin Diseases; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism is a common complication after major orthopedic surgery. When prescribing anticoagulant prophylaxis, clinicians weigh the benefits of thromboprophylaxis against bleeding risk and other adverse events. Previous benefit-risk analyses of the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) randomized clinical studies of rivaroxaban versus enoxaparin after total hip (THA) or knee (TKA) arthroplasty generally used pooled THA and TKA results, counted fatal bleeding as both an efficacy and a safety event, and included the active and placebo-controlled portions of RECORD2, which might confound benefit-risk assessments. We conducted a post hoc analysis without these constraints to assess benefit-risk for rivaroxaban versus enoxaparin in the RECORD studies.. Data from the safety population of the two THA and two TKA studies were pooled separately. The primary analysis compared the temporal course of event rates and rate differences between rivaroxaban and enoxaparin prophylaxis for symptomatic venous thromboembolism plus all-cause mortality (efficacy events) versus nonfatal major bleeding (safety events). Additionally, these rates were used to derive measures of net clinical benefit, number needed to treat (NNT), and number needed to harm (NNH) for these two end points.. After THA or TKA, and compared with enoxaparin, rivaroxaban therapy resulted in more efficacy events prevented than safety events caused, with benefits exceeding harms early and throughout treatment and follow-up. Relative to enoxaparin, rivaroxaban treatment prevented six efficacy events per harm event caused for THA, with NNT =262/NNH =1,711. For TKA, rivaroxaban treatment prevented four to five efficacy events per harm event caused, with NNT =102/NNH =442. Sensitivity analysis that included surgical-site bleeding resulted in NNH =345 for THA and NNH =208 for TKA.. In the RECORD studies, considering death, symptomatic venous thromboembolism, and major bleeding, rivaroxaban resulted in greater benefits than harms compared with enoxaparin. When incorporating surgical-site bleeding, rivaroxaban also results in greater benefit than harm for TKA and is balanced with enoxaparin for THA.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Hemorrhage; Humans; Morpholines; Patient Selection; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Combined anticoagulant and aspirin therapy is associated with increased bleeding risk in patients with atrial fibrillation, but the bleeding risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs) is poorly documented.. To estimate the bleeding risk of combined anticoagulant (rivaroxaban or enoxaparin-vitamin K antagonist [VKA]) and NSAID or aspirin therapy in patients with venous thromboembolism.. Prospective analysis of observational data from the EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and clinics in 8246 patients enrolled from 2007 to 2009.. Bleeding event rates during exposure to NSAID and aspirin therapy were compared to time without exposure.. Days of NSAID or aspirin use and nonuse, clinically relevant bleeding event and major bleeding event rates by patient-years, and hazard ratios.. During NSAID-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 37.5 per 100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID-anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years, compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51-3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]). Major bleeding in aspirin-anticoagulant-treated patients occurred with an event rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA anticoagulation regimens.. Among patients with venous thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or aspirin is associated with an increased risk of clinically relevant and major bleeding.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Drug Therapy, Combination; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Rivaroxaban; Thiophenes; Venous Thromboembolism

The purpose of this drug utilization study was to describe the use of rivaroxaban in Germany during a time period in which approval was limited to the prevention of venous thromboembolism following hip or knee replacement. Additionally, we explored the feasibility of reconstructing inpatient drug use of rivaroxaban in a database where with a few exceptions inpatient prescribing information is not available.. Source of data was one statutory health insurance providing data on about seven million insurants throughout Germany. Analyses were based on a cohort of rivaroxaban users from launch (October 2008) to December 2009 and encompassed potential indications for rivaroxaban use, treatment duration, and co-prescribing of potentially interacting drugs. Start of rivaroxaban treatment was defined by the date of surgery.. During the study period, 425 rivaroxaban users were identified contributing 440 treatment periods. For more than 82% of these episodes labelled indications could be determined. Treatment durations exceeded recommendations in 95% of the episodes following knee replacement whereas rivaroxaban use after elective hip surgery was found to be longer than recommended in 56%. Prescribing of potentially interacting medication was rare except for non-steroidal anti-inflammatory drugs.. Overall, no important off-label use of rivaroxaban was identified. Based on several assumptions that have to be considered in the interpretation of the results our study describes a database approach to reconstruct inpatient drug use for a drug started after a coded hospital procedure, when treatment continues after hospital discharge and no change in drug use is expected in the outpatient setting.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Databases, Factual; Drug Utilization; Factor Xa Inhibitors; Female; Germany; Hospitals; Humans; Male; Middle Aged; Morpholines; Off-Label Use; Rivaroxaban; Thiophenes; Venous Thromboembolism; Young Adult

Patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery are at high risk of developing venous thromboembolism (VTE). Thromboprophylaxis with low-molecular-weight heparin, such as enoxaparin, is standard of care in these patients. Recently, three direct oral anticoagulants (DOACs; dabigatran, rivaroxaban and apixaban), have been approved for this indication, but their cost effectiveness is still unclear as it has usually been extrapolated from surrogate venographic outcomes in clinical trials.. To conduct a pharmacoeconomic evaluation of the DOACs versus subcutaneous (SC) enoxaparin for the prevention of VTE after THR or TKR surgery.. A decision-tree model was developed using TreeAge Pro 2011 to compare the cost utility and cost effectiveness of the DOACs with SC enoxaparin, with separate models for THR and TKR over a 3-month postoperative time horizon from the perspective of the Spanish National Health System. The probabilities of events (symptomatic VTE, clinically relevant bleedings, heparin-induced thrombocytopenia and deaths) were derived from a systematic review and meta-analysis. We used local cost estimates (€2013) and utility values were obtained from the literature. We reported costs, quality-adjusted life-years (QALYs) and symptomatic VTE events. We conducted sensitivity analyses to evaluate parameter uncertainty.. The average costs per 1,000 patients treated with enoxaparin were higher than costs incurred by dabigatran, rivaroxaban and apixaban in THR (€435,208 vs. €283,574, €257,900 and €212,472, respectively) and TKR (€336,550 vs. €219,856, €251,734 and €201,946, respectively), with cost savings ranging from €151,634 to €222,766 in THR, and from €84,816 to €134,604 in TKR. Cost differences were largely driven by differences in costs associated with drug administration. The average QALYs per 1,000 patients treated were very similar for enoxaparin, dabigatran, rivaroxaban and apixaban in THR (199.34, 198.83, 199.08 and 199.68, respectively) and TKR (198.95, 199.41, 198.75 and 199.97, respectively). Rivaroxaban (in TKR and THR) and apixaban (in THR) avoided additional symptomatic VTE events compared with enoxaparin. Sensitivity analyses generally supported the robustness of the analysis to changes in model parameters.. Our model suggests, based on its underlying assumptions and data, that the DOACs are cost-saving alternatives to SC enoxaparin for the prevention of VTE after THR or TKR, in the Spanish healthcare setting.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Dabigatran; Decision Trees; Economics, Pharmaceutical; Enoxaparin; Models, Economic; Pyrazoles; Pyridones; Rivaroxaban; Spain; Treatment Outcome; Venous Thromboembolism

Topics: Enoxaparin; Female; Heart Failure; Humans; Male; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute symptomatic VTE.. Open follow-up study of a cohort of patients aged 18 and over diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) treated with rivaroxaban from December 2011 to January 2014.. The total number of patients treated with rivaroxaban was 103. The mean age was 58+/-17 years. The most frequent co-morbidities were: hypertension (30.0%), dyslipidemia (23.3%) and respiratory disease (25.2%). The type of thromboembolic event treated was: DVT (64.1%), PE (18.4%), DVT+PE (17.5%). Of the rivaroxaban-treated patients, 30% did so from the initial anticoagulant therapy and the other 70% in long-term or extended anticoagulant therapy. The median time of treatment with rivaroxaban was 6 months [corrected]. There was one recurrence and no deaths occurred. Six patients had bleeding, one of which was severe.. Rivaroxaban provides a therapeutic alternative in a group of patients with VTE with advantages over VKAs, because of the convenience in dosing, lack of requirements for periodic monitoring and limited interaction with other drugs.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Selection; Pulmonary Embolism; Recurrence; Risk Factors; Rivaroxaban; Spain; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Topics: Administration, Oral; Adult; Anticoagulants; Antiphospholipid Syndrome; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Administration, Oral; Chromatography, High Pressure Liquid; Drug Overdose; Factor Xa; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Suicide, Attempted; Tandem Mass Spectrometry; Thiophenes; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Drug Substitution; Enoxaparin; Female; Humans; Infant, Newborn; Live Birth; Male; Morpholines; Pregnancy; Pregnancy Complications, Cardiovascular; Recurrence; Risk Factors; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Young Adult

Rivaroxaban is increasingly used to prevent venous thromboembolism after hip or knee arthroplasty. Studies evaluating the effectiveness of rivaroxaban compared to low molecular weight heparin after orthopedic surgery in routine practice are scarce.. We conducted a retrospective cohort study in 121 hospitals in Ontario, Canada, between 2002 and 2012. We included patients aged 66 years or older (median age 73 years) who received an outpatient prescription for subcutaneous low molecular weight heparin (n = 11 471) or oral rivaroxaban (n = 12 850) on hospital discharge after a total knee or hip arthroplasty. The two coprimary outcomes assessed within 30 days of the prescription date were emergency department visit or hospitalization with venous thromboembolism (either deep vein thrombosis or pulmonary embolism; primary efficacy outcome) and a hospitalization with non-traumatic major hemorrhage (primary safety outcome).. Rivaroxaban use increased over the study period. Compared to low molecular weight heparin, rivaroxaban was associated with a lower 30-day risk of hospitalization with venous thromboembolism (0.47% vs. 0.81%; relative risk 0.58; 95% confidence interval 0.42-0.81; P = 0.001) with no significant difference in hospitalizations for major bleeding (0.18% vs. 0.20%; relative risk 0.89; 95% confidence interval 0.50-1.59; P = 0.700).. In routine practice, anticoagulant prophylaxis with rivaroxaban compared to low molecular weight heparin after hospital discharge from total hip or knee arthroplasty is associated with a lower risk of symptomatic venous thromboembolism with no difference in the risk of bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Hip; Humans; Male; Molecular Weight; Morpholines; Ontario; Retrospective Studies; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

This study evaluated differences in medical costs associated with clinical end-points from randomized clinical trials that compared the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, to standard therapy for treatment of patients with venous thromboembolism (VTE).. Event rates of efficacy and safety end-points from the clinical trials (RE-COVER, RE-COVER II, EINSTEIN-Pooled, AMPLIFY, Hokusai-VTE trial) were obtained from published literature. Incremental annual medical costs among patients with clinical events from a US payer perspective were obtained from the literature or healthcare claims databases and inflation adjusted to 2013 costs. Differences in total medical costs associated with clinical end-points for the NOACs vs standard therapy were then estimated. One-way and Monte Carlo sensitivity analyses were carried out.. A lower rate of major bleedings was associated with use of any of the NOACs vs standard therapy. Except for dabigatran, use of NOACs was also associated with a lower rate of recurrent VTE/death. As a result of the reduction in clinical event rates, the overall medical cost differences were -$146, -$482, -$918, and -$344 for VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively, vs patients treated with standard therapy.. When any of the four NOACs are used instead of standard therapy for acute VTE, treatment medical costs are reduced. Apixaban is associated with the greatest reduction in medical costs, which is driven by medical cost reductions associated with both efficacy and safety end-points. Further evaluation may be needed to validate these results in the real-world setting.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Fees, Pharmaceutical; Health Expenditures; Hemorrhage; Humans; Models, Econometric; Monte Carlo Method; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiazoles; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Thiophenes; Venous Thromboembolism

Hypercoagulability, resulting in thromboembolic events, can be a life-threatening complication of nephrotic syndrome (NS). Conventional anticoagulants, such as warfarin, have been the standard of care for more than 50 years; however, the availability of target-specific oral anticoagulants (TSOACs) have provided additional options for the treatment and prevention of thromboembolic events. Documented use of the TSOACs in patients with NS and hypercoagulability is currently limited.. We present the case of an 18-year-old young woman with NS and renal vein thrombosis who was readmitted with bilateral pulmonary emboli on therapeutic doses of warfarin, with a goal international normalized ratio of 2.0 to 3.0. The decision was made to transition the patient from warfarin to rivaroxaban, an oral factor Xa inhibitor.. Rivaroxaban was the first of the emerging TSOACs to be FDA approved for both prevention and treatment of venous thromboembolism. With favorable safety and efficacy data compared with warfarin in addition to a predictable pharmacokinetic profile and the lack of requirement of routine monitoring, rivaroxaban provides a useful alternative in this patient population.. While on therapeutic anticoagulation, a patient previously diagnosed with NS and renal vein thrombosis experienced pulmonary emboli on a conventional anticoagulant and was switched to a target-specific oral anticoagulant with documented completion of 6 months of therapy without recurrent thromboembolism.

Topics: Administration, Oral; Adolescent; Anticoagulants; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Morpholines; Nephrotic Syndrome; Pulmonary Embolism; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism; Warfarin

Oral anticoagulation (OAC) with coumarins and new anticoagulants are highly effective in preventing thromboembolic complications. However, some studies indicate that over- and under-treatment with anticoagulants are fairly common. The aim of this paper is to assess the appropriateness of treatment in patients with a long-term indication for OAC, and to describe the corresponding characteristics of such patients on the basis of screening results from the cluster randomized PICANT trial.. Randomly selected family practices in the federal state of Hesse, Germany, were visited by study team members. Eligible patients were screened using an anonymous patient list that was generated by the general practitioners' software according to predefined instructions. A documentation sheet was filled in for all screened patients. Eligible patients were classified into 3 categories (1: patients with a long-term indication for OAC and taking anticoagulants, 2: patients with a long-term indication for OAC but not taking anticoagulants, 3: patients without a long-term indication for OAC but taking an anticoagulant on a permanent basis). IBM SPSS Statistics 20 was used for descriptive statistical analysis.. We screened 2,036 randomly selected, potentially eligible patients from 52 family practices. 275 patients could not be assigned to one of the 3 categories and were therefore not considered for analysis. The final study sample comprised 1,761 screened patients, 1,641 of whom belonged to category 1, 78 to category 2, and 42 to category 3. INR values were available for 1,504 patients of whom 1,013 presented INR values within their therapeutic ranges. The majority of screened patients had very good compliance, as assessed by the general practitioner. New antithrombotic drugs were prescribed in 6.1% of cases.. The screening results showed that a high proportion of patients were receiving appropriate anticoagulation therapy. The numbers of patients with a long-term indication for OAC therapy that were not receiving oral anticoagulants, and without a long-term indication that were receiving OAC, were considerably lower than expected. Most patients take coumarins, and the quality of OAC control is reasonably high.. Current Controlled Trials ISRCTN41847489.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Coumarins; Dabigatran; Family Practice; Female; Germany; Guideline Adherence; Heart Diseases; Heart Valve Prosthesis; Humans; International Normalized Ratio; Male; Mass Screening; Middle Aged; Morpholines; Practice Guidelines as Topic; Process Assessment, Health Care; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Thrombosis; Venous Thromboembolism

To address common "what if" questions that arise relating to the long-term clinical follow-up and management of patients receiving the new oral anticoagulants (NOACs).. For this narrative review, we searched the PubMed database for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation and for the treatment of acute venous thromboembolism. We used this evidence base to address prespecified questions relating to NOAC use in primary care settings.. Dabigatran and rivaroxaban should be taken with meals to decrease dyspepsia and increase absorption, respectively. There are no dietary restrictions with any of the NOACs, beyond moderating alcohol intake, and rivaroxaban and apixaban can be crushed if required. The use of acid suppressive therapies does not appear to affect the efficacy of the NOACs. As with warfarin, patients taking NOACs should avoid long-term use of nonsteroidal anti-inflammatory and antiplatelet drugs. For patients requiring surgery, generally NOACs should be stopped 2 to 5 days before the procedure, depending on bleeding risk, and the NOAC should usually be resumed at least 24 hours after surgery. Preoperative coagulation testing is generally unnecessary. In patients who develop bleeding, minor bleeding typically does not require laboratory testing or discontinuation of NOACs; with major bleeding, the focus should be on local measures to control the bleeding and supportive care, and coagulation testing should be performed. There are currently no antidotes to reverse NOACs. The NOACs should not be used in patients with valvular heart disease, prosthetic heart valves, cancer-associated deep vein thrombosis, or superficial thrombophlebitis.. Management of "what if" scenarios for patients taking NOACs have been proposed, but additional study is needed to address these issues, especially periprocedural management and bleeding.

Topics: Acute Disease; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Family Practice; Hemorrhage; Humans; Morpholines; Preoperative Care; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Time Factors; Venous Thromboembolism

The percentage of time during which the patients have the INR within the target values (i.e. Time in Therapeutic Range [TTR]) is a measure of anticoagulation quality with Vitamin K Antagonists (VKA). To evaluate the quality of anticoagulation using TTR according to the Rosendaal method, we performed an observational, retrospective study. We included all outpatients who attended the cardiology anticoagulation clinic of a Portuguese hospital (2011-2013), whose target INR was 2.0-3.0.. 377 VKA-treated patients were evaluated. Of these, 72.4% had non-valvular atrial fibrillation. Patients were followed for a mean period of 471 days. The mean TTR was 60.3% (SD 19.3%) and 44.3% of the patients had a mean TTR<60%. Patients were at high risk of bleeding (INR>4.5) and at high thrombotic risk (INR<1.5) during, respectively, 1.7% and 4.7% of the time.. Anticoagulation control needs to be improved. These results are informative for all stakeholders: patients, health care professionals, and policymakers.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Hemorrhage; Hospitals; Humans; International Normalized Ratio; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Venous Thromboembolism; Warfarin

Topics: Administration, Oral; Anticoagulants; Chemoprevention; Costs and Cost Analysis; Humans; Morpholines; Orthopedic Procedures; Orthopedics; Outcome Assessment, Health Care; Postoperative Complications; Retrospective Studies; Rivaroxaban; Russia; Secondary Prevention; Thiophenes; Traumatology; Venous Thromboembolism

Rivaroxaban is the first licensed oral direct inhibitor of factor Xa. Recent studies from the RECORD trials suggest rivaroxaban has superior efficacy compared to enoxaparin in preventing venous thromboembolism (VTE) with no significant increase in the major bleeding risk. Concerns remain regarding the incidence of minor bleeding, consequent delayed wound healing and subsequent risk of infection. The aim of this observational study was to assess the incidence of post-operative complications in patients receiving either rivaroxaban or enoxaparin thromboprophylaxis following elective hip and knee arthroplasty.. A total of 258 patients undergoing elective total hip or knee arthroplasty within one NHS Trust were included. A total of 202 subjects (mean age, 70.7 years ± 10.0, 43 % men) received a daily dose of 10 mg of oral rivaroxaban and 56 (mean age, 70.9 years ± 9.8, 39 % men) had a daily subcutaneous injection of 40 mg of enoxaparin as thromboprophylaxis. Endpoints included VTE (deep vein thrombosis and pulmonary embolism), haemorrhagic wound complications, hospital re-admission, requirement for blood transfusion, minor and major bleeding and death.. There were no significant differences in the incidence of VTE, requirement for blood transfusion and readmission rate between rivaroxaban and enoxaparin-treated patients. The incidence of minor bleeding (2.0 vs. 0 %) and haemorrhagic wound complications (5.0 vs. 1.8 %) were non-significantly higher in the rivaroxaban-treated group. There were no cases of pulmonary embolism, major bleeding or death in either group.. Our experience with rivaroxaban in elective hip and knee arthroplasty showed no significant difference in the incidence of VTE or major bleeding. There was, however, a tendency to greater risk of minor bleeding and wound complications that were largely haemorrhagic in nature, which may have reached significance in a larger study.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Chemoprevention; Elective Surgical Procedures; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Osteoarthritis, Hip; Osteoarthritis, Knee; Outcome and Process Assessment, Health Care; Postoperative Complications; Rivaroxaban; Thiophenes; United Kingdom; Venous Thromboembolism; Wound Healing

Rivaroxaban is a direct factor Xa inhibitor, which is rapidly absorbed in the upper gastrointestinal (GI) tract. In large trials, it has been shown to be effective and safe in VTE treatment. However, in these trials patients with morbid obesity were not reported and it is unknown if the standard dosage of 20 mg rivaroxaban is sufficient for bariatric patients, especially after bariatric surgery, which may impact the resorption of rivaroxaban. We report the case of a bariatric patient with high venous thromboembolism risk and instable INR after recent bariatric surgery, who was switched from Vitamin-K antagonists to rivaroxaban. After intake of 20 mg rivaroxaban, plasma concentration were repeatedly measured until 3 h after the second dose using a commercially available chromogenic aXa-assay. Furthermore, INR and aPTT were measured. Peak concentrations of 224.22 ng/ml were observed. After 6 h, plasma concentration decreased to 86.9 ng/ml and remained stable until 12 h (86.32 ng/ml). After 24 h, a trough level of 35.54 ng/ml was observed. The patients INR did immediately increase and remained significantly elevated throughout the day with a slow decrease. Since peak values of rivaroxaban plasma concentrations were in the expected range of published data, we conclude that resorption of rivaroxaban was immediate and not significantly impaired by bariatric surgery of the upper GI tract. Consequently, no dose adjustments seem to be necessary in this high-risk population.

Topics: Adult; Anticoagulants; Bariatric Surgery; Female; Humans; International Normalized Ratio; Morpholines; Obesity, Morbid; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K

Pharmacologic prophylaxis with low-dose unfractionated heparin, low molecular weight heparin or fondaparinux has clearly demonstrated to reduce the rate of thromboembolic events in surgical patients. In the last decade, several novel oral anticoagulants have been tested in surgical patients, but only in the setting of major orthopedic surgery. Based on the results of the studies, dabigatran, rivaroxaban and apixaban have been approved by the European Medicines Agency for the prevention of venous thromboembolism after elective hip or knee replacement surgery. The novel anticoagulants represent an appealing alternative to current prophylaxis strategies that are mostly based on subcutaneous injection of low molecular weight heparin and have also been recommended by recently updated guidelines. Their role in other settings, such as hip fracture surgery, or in non-orthopedic surgery, may deserve future evaluation.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Rivaroxaban is a direct inhibitor of activated factor X, and dabigatran is a direct inhibitor of thrombin. These new oral anticoagulants have demonstrated to be effective and safe in clinical trials on the treatment of venous thromboembolic disease (deep vein thrombosis and pulmonary thromboembolism).

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed. This has resulted in unacceptable rates of morbidity and mortality.. The Southern African Society of Thrombosis and Haemostasis held a meeting to update the previous guideline and review new literature including guidelines from other societies. The following specialties were represented on the committees: anaesthetics, cardiology, clinical haematology, critical care, obstetrics and gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery and pulmonology. A draft document was presented at the meeting, which was then revised by consensus agreement. To avoid local bias, the guideline was adjudicated by recognised international external experts.. A concise, practical updated guideline for thromboprophylaxis and treatment in medical and surgical patients has been produced for South African conditions. It is hoped that this guideline will continue to improve anticoagulation practice in this country, which we believe will directly benefit patient outcomes.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Chemoprevention; Dabigatran; Disease Management; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Monitoring; Drug Substitution; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Morpholines; Preoperative Care; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Thiophenes; Time Factors; Vena Cava Filters; Venous Thromboembolism

Pulmonary embolism is a leading cause of fatality in elective orthopaedics. Recently introduced oral thromboprophylaxis (rivaroxaban) has a logistic advantage but has also raised early concerns amongst arthroplasty surgeons. The aim of this study was to evaluate the impact of rivaroxaban as a chemical thromboprophylaxis following knee arthroplasty in reference to radiologically diagnosed PE and return to theatre following wound complication.. Following the introduction of new NICE guidelines in our institute 266 consecutive TKR receiving rivaroxaban were studied prospectively and compared with retrospectively collected consecutive 596 TKR prior to adoption of the guidelines. Both of these groups were studied for radiologically diagnosed symptomatic VTE episodes within 90days and return to theatre following wound complication.. A total of 862 cases were studied, out of which 596 were in the retrospective control group and 266 were in the prospective rivaroxaban group. Both the groups had a female predominance with a mean age at the time of surgery as 68 and 69 in control and prospective cohort respectively. There were 24 radiologically diagnosed symptomatic PE and one DVT in the control group whereas, the rivaroxaban prospective group had 2 PE and 2 DVT cases. The return to theatre following wound complication was 2 and 7 in control and prospective group respectively.. Following the introduction of rivaroxaban the number of symptomatic radiologically confirmed PE events declined (p=0.0084) but the return to theatre rate due to wound complications increased (p=0.0049).. III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Case-Control Studies; Female; Follow-Up Studies; Humans; Middle Aged; Morpholines; Postoperative Complications; Primary Prevention; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Rivaroxaban; Survival Rate; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Oral anticoagulants block the coagulation cascade either by an indirect mechanism (e.g., vitamin K antagonists) or by a direct one (e.g., the novel oral anticoagulants). Vitamin K antagonists are widely used as treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. Although low molecular weight heparin remains the first line in venous thromboembolism prophylaxis, more recently the novel oral anticoagulants such as dabigatran (initial dose of 110 mg within 1-4 h after surgery, followed by the full dose of 220 mg once daily), rivaroxaban (dose of 10 mg once daily, with the first dose administered 6-10 h after the surgery), and apixaban (dose of 2.5 mg twice daily, starting 12-24 h after surgery, but available only in Europe) are approved for prophylaxis in patients undergoing major orthopedic surgery. The period in which thromboembolic risk abates remains uncertain, and trials of extended therapy are still ongoing. After showing at least noninferiority to warfarin in RE-LY, ROCKET-AF, and ARISTOTLE trials, dabigatran (110 or 150 mg twice daily), rivaroxaban (20 or 15 mg once daily), and apixaban (5 mg twice daily), respectively, were approved also for stroke prevention in patients with atrial fibrillation. While awaiting long-term safety data, the choice among all these available therapies should be based on patient preferences, compliance, and ease of administration, as well as on local factors affecting cost-effectiveness.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Humans; Morpholines; Orthopedic Procedures; Practice Guidelines as Topic; Prognosis; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Humans; Male; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Long-Term Care; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Secondary Prevention; Thiophenes; Venous Thromboembolism

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Interactions; Humans; Medication Adherence; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Rivaroxaban (with initial increased dosage) may be used as a stand-alone therapy in patients with venous thrombo-embolism. The development of new anticoagulant drugs opened several options in the management of venous thrombo-embolism. The efficacy and safety of these new oral anticoagulants in specific population as elderly and those with renal impairment deserve future research. At that time, only rivaroxaban is licensed in France, in the treatment of deep venous thrombosis.

Topics: Administration, Oral; Anticoagulants; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Several new oral anticoagulants are now on the Swiss market and the general practitioner faces new challenges regarding the management of these new drugs. This consensus document aims to answer to the most frequently asked questions regarding rivaroxaban and covers different topics such as indications, initiation of treatment, drug-drug interactions and perioperative management.

Topics: Administration, Oral; Anticoagulants; General Practice; Humans; Morpholines; Orthopedic Procedures; Rivaroxaban; Switzerland; Thiophenes; Treatment Outcome; Venous Thromboembolism

Rivaroxaban is an oral direct factor Xa inhibitor that is noninferior to warfarin in the prevention of recurrent venous thromboembolism (VTE). Whether rivaroxaban is cost-effective in the prevention of recurrent VTE, however, is not known.. To assess the cost effectiveness of rivaroxaban compared with warfarin in the prevention of recurrent VTE, we built a Markov state-transition model over a 10-year time horizon. The base case analysis consisted of a hypothetical cohort of 60-year-old patients with an initial VTE who received secondary prophylaxis with either rivaroxaban or warfarin for 3 to 12months. Cost estimates were derived from the Healthcare and Utilization Project and other sources. Probabilities were based on literature values. Outcomes included costs in 2011 United States dollars, quality-adjusted life-years (QALYs), and incremental cost effectiveness ratios (ICERs) over 10years from a societal perspective.. Compared with warfarin, the rivaroxaban strategy cost less ($3,195 vs. $6,188) and was more effective (9.29 QALYs vs 9.14 QALYs). Our results were highly robust in sensitivity analyses. Warfarin was no longer dominated by rivaroxaban when the risk of major bleeding with rivaroxaban exceeds 3.8% (base case estimate: 0.96%).. In summary, prophylactic anticoagulation with rivaroxaban appears to be a cost effective, and perhaps cost saving, alternative to warfarin for the prevention of recurrent VTE.

Topics: Anticoagulants; Cohort Studies; Cost-Benefit Analysis; Female; Humans; Male; Markov Chains; Middle Aged; Morpholines; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; United States; Venous Thromboembolism; Warfarin

After 60 years in which warfarin has been the only practical oral anticoagulant, a number of new oral anticoagulants are entering practice. These drugs differ in a several important respects from warfarin; most notably they have a reliable dose-response effect which means they can be given without the need for monitoring. Their simpler metabolism and mode of action also results in fewer interactions with other drugs and with diet. However, some of their other properties such as renal clearance (to varying degrees), short half-life and lack of an available antidote may slow their rate of introduction. Large trials have established their non-inferiority to warfarin in a number of indications and in some cases their superiority. To date they have been licensed for prophylaxis following high risk orthopaedic procedures, non-valvular atrial fibrillation and treatment of venous thromboembolism, but is not clear that they will supplant warfarin in all areas.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Canada; Contraindications; Dabigatran; Drug Dosage Calculations; Drug Interactions; Humans; Morpholines; Postoperative Complications; Pyridines; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis

No routine coagulation laboratory test is recommended during rivaroxaban or dabigatran treatment. However measuring drug concentration and/or anticoagulant activity can be desirable in some special clinical settings, such as bleeding, thrombosis recurrence or emergency surgery. The effects of dabigatran etexilate and rivaroxaban on various coagulation assays have been previously studied in normal plasma spiked with increasing concentrations of the drug. In contrast, few data are available in routinely treated patients. In order to perform and to interpret the results of these tests, it is necessary to determine the usual responses of patient's plasma. We have used several coagulation tests in a prospective study including 106 patients receiving thromboprophylactic treatment with dabigatran 150 or 220 mg od and rivaroxaban 10 mg od for major orthopaedic surgery. The most common tests--prothrombin time (PT) and activated partial thromboplastin time (aPTT)--give results, which vary according to the reagent used. To overcome this limitation, we advocate the use of plasma calibrators, which decreases the inter-laboratory heterogeneity of results. Anti-Xa measurement and Hemoclot, a thrombin diluted clotting assay, are specific assays which have been proposed for rivaroxaban and dabigatran respectively. These tests, conventional PT, aPTT and thrombin generation (TG) have been performed. We demonstrated that measurements of both drugs can determine reliably the drug concentration in patients' plasmas. PT is more prolonged with rivaroxaban than with dabigatran. Interestingly, the pattern of TG was clearly different in relation to the difference in the mechanism of action of the two new anticoagulants. A significant inter-individual variability of response is detected. Rivaroxaban--mean Cmax 140 ng/mL (extremes 0-412) induces a greater increase of PT than dabigatran. aPTT is sensitive to dabigatran. Rivaroxaban concentrations were in good agreement with two other studies while unexplained lower than expected concentrations were found in dabigatran patients receiving 220 mg once a day [mean Cmax 60 ng/mL (extremes 0-320)]. An interference by pantoprazole, a drug which reduces dabigatran absorption, could explain the observed lower than expected results.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Blood Coagulation Tests; Dabigatran; Female; Humans; Male; Middle Aged; Morpholines; Orthopedic Procedures; Primary Prevention; Rivaroxaban; Thiophenes; Venous Thromboembolism

We report on a 61-year-old female patient who developed a spontaneous spinal epidural haematoma (SSEH) after being treated by rivaroxaban, a new agent for the prevention of venous thromboembolic events in orthopaedic surgery. Although the pathogenesis of SSEH is unclear, anticoagulant therapy is a known risk factor. The patient sustained a sudden onset of severe back pain in the thoracic spine, followed by paraplegia below T8, 2 days after proximal tibial osteotomy and rivaroxaban therapy. Magnetic resonance imaging (MRI) of the whole spine demonstrated a ventral SSEH from C2 to T8. Whilst preparing for the emergency evacuation of the SSEH, the neurological symptoms recovered spontaneously 4 h after onset without surgery. After monitored bed rest for 48 h the MRI was repeated and the SSEH was no longer present. This rare condition of spinal cord compression and unusually rapid spontaneous recovery has not previously been reported following rivaroxaban therapy.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Hematoma, Epidural, Spinal; Humans; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Major orthopaedic surgery, such as total hip replacement (THR) and total knee replacement (TKR), is associated with an increased risk of venous thromboembolism (VTE).. Clinical trials have demonstrated the efficacy of rivaroxaban, a once-daily, orally administered Factor Xa inhibitor, for the prevention of VTE in patients undergoing THR or TKR. This analysis evaluated the cost effectiveness of rivaroxaban compared with enoxaparin, from a U.S. payer's perspective.. A decision-analytic model was developed to compare the costs and outcomes associated with rivaroxaban and enoxaparin for the prevention of VTE. The model replicated short-term clinical outcomes from the phase III RECORD trials. RECORD1 and RECORD2 compared rivaroxaban 10 mg daily (qd), given for 35 days, with enoxaparin 40 mg qd, given for 35 days or 10 to 14 days, respectively, in patients undergoing THR. RECORD3 compared 10 mg of rivaroxaban qd for 10 to 14 days versus 40 mg of enoxaparin qd for 10 to 14 days in patients undergoing TKR. The decision-analytic model also included data on long-term complications and sequelae as captured in observational studies and databases. It also included direct year 2010 medical costs over 1-year and 5-year time horizons. A series of sensitivity analyses were performed to determine the impact of different factors on the results of the model. Results of the cost-effectiveness analysis were reported in terms of symptomatic VTE events avoided.. Rivaroxaban was associated with cost savings of $US 511.93 per patient and prevented an average of 0.0145 symptomatic VTE events per patient in the THR population, compared with enoxaparin. For a TKR population, 10 to 14 days of rivaroxaban prophylaxis was associated with cost savings of $US 465.74 and prevented an average 0.0193 symptomatic VTE events per patient. Sensitivity analysis suggested that the results of the model were robust, with cost savings ranging from $US 133.96-629.57 in the THR population and $US 293.01-848.68 in the TKR population, depending on the variables used. Sensitivity analysis also suggested that the economic profile of rivaroxaban is improved when the time horizon of the model is extended from 1 year to 5 years. A probabilistic sensitivity analysis confirmed the findings of baseline results, showing that rivaroxaban was less costly and more effective in all model simulations for both populations.. This decision-analytic model analysis, from the U.S. payer's perspective, concluded that rivaroxaban may be cost saving in both the THR and the TKR populations, when compared with enoxaparin in the U.S.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Enoxaparin; Humans; Middle Aged; Models, Economic; Morpholines; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; United States; Venous Thromboembolism

This study assesses the use of new anticoagulants for the prevention of venous thromboembolism (VTE) in patients undergoing elective orthopedic surgery using traditional cost-effectiveness analysis and efficiency frontier methodology.. Efficiency frontier methodology has the potential to systematically improve the information used in policy and decision making, though it is still relatively uncommon in health economics. Anticoagulation in elective orthopedic surgery provides a fitting and timely case study for examining the influence of choosing one methodology over another.. An economic model was developed to capture the relative benefits and consequences of choosing one anticoagulation strategy over another in the context of orthopedic surgery. Three novel oral anticoagulants (apixaban, rivaroxaban, dabigatran) are compared with enoxaparin 40 mg daily from the UK National Health Service perspective using traditional cost-effectiveness estimates (cost/quality-adjusted life years, cost/life years gained) and the efficiency frontier. The latter explicitly includes embolic and bleeding events as outcomes. A 5-year time horizon was adopted.. Total discounted costs ranged from about £200 000 to £431 000 over 5 years per 1000 patients undergoing elective total hip arthroplasty, and from £243 000 to £463 000 per 1000 patients for elective total knee arthroplasty. Analysis of the efficiency frontier demonstrates that apixaban and rivaroxaban are the preferred choices, depending on the outcome examined and the type of surgery. In terms of safety, apixaban is associated with more bleeding events avoided; yet, rivaroxaban demonstrated better VTE outcomes.. Traditional cost-effectiveness analysis systematically excludes information related to the safety profiles of these anticoagulants. The efficiency frontier approach presented in this study provides critical information, without substantial effort, to permit a fully informed decision by taking into account all relevant outcomes as they relate to the costs associated with treatment choice.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Decision Trees; Drug Costs; Elective Surgical Procedures; Enoxaparin; Female; Humans; Male; Markov Chains; Models, Economic; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Rivaroxaban; State Medicine; Thiophenes; United Kingdom; Venous Thromboembolism

Several key reports from the American Heart Association meeting, held in Orlando (FL, USA) in November 2011, are presented related to anti-thrombotic therapy in acute coronary syndrome and the use of dronedarone in permanent atrial fibrillation is discussed in this brief (and selective) overview of this meeting. A summary of the ATLAS-TIMI-51, TRACER and PALLAS trials is provided.

Topics: Acute Coronary Syndrome; American Heart Association; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Dronedarone; Fibrinolytic Agents; Humans; Lactones; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Treatment Outcome; United States; Venous Thromboembolism

Topics: Anticoagulants; Female; Humans; Male; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

A cost-effectiveness model for rivaroxaban evaluated the cost-effectiveness of prophylaxis with rivaroxaban (a once-daily, orally administered Factor Xa inhibitor) vs enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR). This Canadian analysis was conducted using the Ontario Ministry of Health perspective over a 5-year time horizon. The model combined clinical data and builds upon existing economic models.. The model included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with 1-year cycles) phases. The model allowed VTE event rates, quality-adjusted life expectancy and direct medical costs to be estimated over a 5-year time horizon, based on current approved practice patterns in Canada. A number of one-way sensitivity analyses were performed on the baseline assumptions, including a comparison of rivaroxaban with dalteparin, and probabilistic sensitivity analyses were performed to address any uncertainty concerning model inputs.. When comparing equal durations of therapy, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more benefit at a lower cost. Rivaroxaban was cost-effective when comparing 35 days' prophylaxis with 14 days' prophylaxis with enoxaparin following THR. One-way and probabilistic sensitivity analyses demonstrated that the results of the economic analysis were robust to variations in key inputs. Rivaroxaban remained dominant during one-way sensitivity analyses comparing rivaroxaban with dalteparin after THR or TKR.. Although clinical trial data were used in the prophylaxis module, assumptions and values used in the post-prophylaxis and long-term complication (LTC) modules were based on several different literature sources; it was not always possible to source Canadian data.. This economic analysis suggests that the use of rivaroxaban for the prophylaxis of VTE after THR or TKR in Canada was cost-effective.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Cost-Benefit Analysis; Humans; Morpholines; Ontario; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Interactions; Humans; Morpholines; Postoperative Complications; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Aged; Anesthesia, Conduction; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Administration Schedule; Female; Hip Prosthesis; Humans; Morpholines; Obesity; Postoperative Complications; Postoperative Hemorrhage; Practice Guidelines as Topic; Premedication; Prosthesis Failure; Recurrence; Reoperation; Risk; Risk Factors; Rivaroxaban; Stockings, Compression; Thiophenes; Venous Thromboembolism

Topics: Acute Disease; Anticoagulants; Evidence-Based Medicine; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

The National Centre for Pharmacoeconomics, in collaboration with the Health Services Executive, considers the cost effectiveness of all new medicines introduced into Ireland. Health Technology Assessments (HTAs) are conducted in accordance with the existing agreed Irish HTA guidelines. These guidelines do not specify a formal analysis of value of information (VOI).. The aim of this study was to demonstrate the benefits of using VOI analysis in decreasing decision uncertainty and to examine the viability of applying these techniques as part of the formal HTA process for reimbursement purposes within the Irish healthcare system.. The evaluation was conducted from the Irish health payer perspective. A lifetime model evaluated the cost effectiveness of rivaroxaban, dabigatran etexilate and enoxaparin sodium for the prophylaxis of venous thromboembolism after total hip replacement. The expected value of perfect information (EVPI) was determined directly from the probabilistic analysis (PSA). Population-level EVPI (PEVPI) was determined by scaling up the EVPI according to the decision incidence. The expected value of perfect parameter information (EVPPI) was calculated for the three model parameter subsets: probabilities, preference weights and direct medical costs.. In the base-case analysis, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. PSA indicated that rivaroxaban had the highest probability of being the most cost-effective strategy over a threshold range of &U20AC;0-&U20AC;100 000 per QALY. At a threshold of &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy was 67%. At a threshold of &U20AC;45 000 per QALY, assuming a 10-year decision time horizon, the PEVPI was &U20AC;11.96 million and the direct medical costs subset had the highest EVPPI value (&U20AC;9.00 million at a population level). In order to decrease uncertainty, a more detailed costing study was undertaken. In the subsequent analysis, rivaroxaban continued to dominate both comparators. In the PSA, rivaroxaban continued to have the highest probability of being optimal over the threshold range &U20AC;0-&U20AC;100 000 per QALY. At &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy increased to 80%. At &U20AC;45 000 per QALY, the 10-year PEVPI decreased to &U20AC;3.58 million and the population value associated with the direct medical costs fell to &U20AC;1.72 million.. This increase in probability of cost effectiveness, coupled with a substantially reduced potential opportunity loss could influence a decision maker's confidence in making a reimbursement decision. On discussions with the decision maker we now intend to incorporate the use of VOI into our HTA process.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Decision Making; Enoxaparin; Guidelines as Topic; Health Care Costs; Humans; Ireland; Models, Economic; Morpholines; Pyridines; Quality-Adjusted Life Years; Rivaroxaban; Technology Assessment, Biomedical; Thiophenes; Time Factors; Venous Thromboembolism

Patients undergoing major orthopedic surgery, including total hip arthroplasty (THA) and total knee arthroplasty (TKA), are at high risk for developing venous thromboembolism (VTE). Although largely a preventable complication, VTE develops in a significant proportion of patients, highlighting the need for improved methods of VTE prevention. Current thromboprophylactic options are limited by unpredictable pharmacokinetics and pharmacodynamics (vitamin K antagonists), parenteral/subcutaneous administration (heparin and low-molecular-weight heparins), complicated dosing, and increased risk of bleeding.Rivaroxaban is an oral, direct Factor Xa inhibitor that has recently received marketing authorization in the United States for prophylaxis of deep vein thrombosis in patients undergoing hip or knee replacement surgery. The clinical pharmacology of rivaroxaban supports a convenient, oral, once-daily dosing regimen without the need for routine coagulation monitoring after THA or TKA. A comprehensive phase II and III study program supports its safety and efficacy for VTE prevention after THA or TKA. Phase III results have demonstrated the superior efficacy of rivaroxaban regimens compared with enoxaparin regimens, with similar rates of major bleeding. This article provides an overview of the phase II and III results that support the use of this agent for the prevention of VTE after elective total hip or knee replacement.

Topics: Administration, Oral; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism is a frequent and potentially life-threatening complication of orthopedic surgery. Rivaroxaban is an oral direct factor Xa inhibitor, which was shown to be effective for the prevention of venous thromboembolism after elective hip and knee arthroplasty in the RECORD study program. Rivaroxaban has the potential to overcome the limitations of the current standards of care in the prevention of venous thromboembolism. XAMOS (Xarelto(®) in the prophylaxis of post-surgical venous thromboembolism after elective major orthopedic surgery of hip or knee) is an international, noninterventional, parallel-group study to gain insight into the safety (major bleeding, side effects) and effectiveness (prevention of symptomatic thromboembolic events) of rivaroxaban in daily clinical practice. XAMOS will follow 15,000 patients after major orthopedic surgery in approximately 200 centers worldwide, with about 7500 patients receiving rivaroxaban and about 7500 standard of care. XAMOS will supplement the clinical data obtained in the Phase III RECORD 1, 2, 3, and 4 trials in which rivaroxaban was shown to be superior for the primary efficacy endpoints, and with a safety profile similar to that of enoxaparin after hip or knee replacement surgery. XAMOS was started in 2009 and will complete recruitment and follow-up in 2011.

Topics: Anticoagulants; Hemorrhage; Hip Joint; Humans; Knee Joint; Morpholines; Orthopedic Procedures; Registries; Research Design; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Patients undergoing major orthopaedic surgery (MOS), such as total hip (THR) or total knee replacement (TKR), are at high risk of developing venous thromboembolism (VTE). For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG) system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI) and the German hospital perspective.. To assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI) perspective and to analyse financial incentives from the German hospital perspective.. Based on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR) and two perspectives (SHI and hospital) per setting.. Prophylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR) compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (€27.3 saving per patient treated). However, the cost-effectiveness after THR (€17.8 cost per person) remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by €20.6 (TKR) and €31.8 (THR) per case respectively.. Based on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Databases, Factual; Decision Trees; Enoxaparin; Germany; Humans; Morpholines; Multicenter Studies as Topic; National Health Programs; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Thromboprophylaxis with rivaroxaban (R) is superior to enoxaparin in patients undergoing major orthopedic surgery (MOS). However, rivaroxaban has never been directly compared with fondaparinux (F), which also shows superior efficacy over enoxaparin. The clinical impact of switching from fondaparinux to rivaroxaban thromboprophylaxis is unclear.. To evaluate the efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in unselected patients undergoing MOS.. This is a monocentric, retrospective cohort study in 5061 consecutive patients undergoing MOS at our centre, comparing rates of symptomatic VTE, bleeding and surgical complications, length of hospital stay and risk factors for VTE.. Rates of symptomatic VTE were 5.6% (F) and 2.1% (R; P < 0.001), with rates for distal DVT being 3.9 vs. 1.1% (P < 0.001). Rates of major VTE were numerically higher with fondaparinux (1.8 vs. 1.1%), but not statistically significant. Rates of severe bleeding (bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban compared with fondaparinux (2.9 vs. 4.9%; P = 0.010). The mean length of hospital stay was significantly shorter in the rivaroxaban group (8.3 days, 95% CI 8.1-8.5 vs. 9.3 days, 9.1-9.5; P < 0.001).. Based on an indirect comparison of two consecutive cohorts, our data suggest that thromboprophylaxis with rivaroxaban is associated with less VTE and bleeding events than fondaparinux in unselected patients undergoing MOS. Prospective comparisons are warranted to confirm our findings.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Tests; Drug Administration Schedule; Female; Fondaparinux; Germany; Humans; Kaplan-Meier Estimate; Logistic Models; Longevity; Male; Middle Aged; Morpholines; Orthopedic Procedures; Polysaccharides; Postoperative Hemorrhage; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

Approximately 6 million Americans are treated with chronic anticoagulation. Of these, 10% of patients will require temporary anticoagulation interruption for an invasive procedure each year. Anticoagulation management during this period requires a formal strategy in order to limit both bleeding and thromboembolic complications. This article will give health care providers a stepwise approach to this process. The first step is to determine whether warfarin discontinuation is necessary for the planned procedure. For procedures requiring warfarin discontinuation, the second step is to determine the appropriate timing. The third step is to identify the patient-specific thromboembolic risk in order to determine which patients require bridging therapy with parenteral anticoagulants. The fourth step is both the most complicated and most critical step in this management strategy. This decision-making step involves choosing the appropriate anticoagulant regimen, dose, and timing of reinitiation that is best tailored to a specific patient, as well as determining procedural variables, in order to limit bleeding and thrombotic complications.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Coronary Restenosis; Dabigatran; Heart Valve Prosthesis; Hemorrhage; Humans; Morpholines; Neoplasms; Perioperative Care; Risk Assessment; Rivaroxaban; Stents; Thiophenes; Venous Thromboembolism; Warfarin

Post-operative complications after total hip or knee replacement can delay recovery, prolong hospitalisation, increase rates of re-admission and, in the most severe cases, lead to long-term disability or even death. In this analysis of pooled data from four large, randomised, phase III clinical trials that compared the oral, direct Factor Xa inhibitor rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement (n = 12,729), the incidence of complications, including bleeding and adverse events related to surgery (such as wound infection, wound dehiscence and haemarthrosis) are reported. Interventions and procedures relating to surgery are also compared between the groups. Bleeding events, including excessive wound haematoma and surgical-site bleeding, occurred at similar rates in the rivaroxaban and enoxaparin groups. Over the total study duration, adverse surgical events occurred at a similar rate in the rivaroxaban group compared with the enoxaparin group after total knee replacement (2.26% vs. 2.69%, respectively) and total hip replacement (1.48% vs. 1.65%, respectively). Blood loss, wound drainage and transfusion requirements were also similar between the two groups. This analysis shows that the incidence of adverse surgical events with rivaroxaban was similar to enoxaparin.

Topics: Anticoagulants; Arthroplasty, Replacement, Ankle; Arthroplasty, Replacement, Knee; Clinical Trials, Phase III as Topic; Enoxaparin; Hemarthrosis; Hemorrhage; Humans; Morpholines; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

For the last 60 years, heparin and vitamin K antagonists have been the cornerstone of anticoagulation. Nowadays, the new anticoagulants, such as dabigatran, rivaroxaban and apixaban, show potential advantages over classical treatments. These agents inhibit specific coagulation factors and are administered orally at fixed doses. Furthermore, heparin and vitamin K antagonists have a fast onset of action, short-duration and predictable therapeutic effects. No interactions with foods have been described, although some drug-drug interactions have been reported. At the moment, no antidotes are available. However, due to the short half-life of these agents, antidotes are less essential. The new anticoagulants are at least as effective and safe as traditional treatments in the prevention of venous thromboembolism after orthopedic surgery, as well as in the prevention of stroke and systemic embolism in non-valvular atrial fibrillation. Dabigatran and rivaroxaban have also been shown to be effective in the treatment of acute venous thromboembolism. Due to their properties, these drugs could gradually replace heparin and especially vitamin K antagonists. Hopefully, many of our patients will be able to discontinue classical anticoagulant treatment and others will never begin it.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Venous Thromboembolism; Warfarin

Rivaroxaban is a direct oral anticoagulant targeting factor Xa. Efficacy and safety of rivaroxaban were evaluated through the phase 3 EINSTEIN program, consisting in three clinical trials regarding the treatment of deep vein thrombosis (EINSTEIN DVT), pulmonary embolism (EINSTEIN PE), and in secondary prevention after a first episode of venous thromboembolic disease (EISNTEIN EXT). Rivaroxaban was recently approved both by the European and the French Health agencies for the treatment of DVT and prevention of deep vein thrombosis recurrence. This report addresses the use of rivaroxaban in clinical practice in such indications.

Topics: Age Factors; Anticoagulants; Drug Interactions; Factor Xa; France; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamins

New oral anticoagulants are already or will be soon available. They have shown good efficacy and safety in various studies (prevention and treatment of venous thromboembolism, atrial fibrillation). Their arrival will probably modify the prescription of the current anticoagulant agents. However some precaution should be given in their use pending post marketing studies. Although these new drugs are intended to replace mostly vitamin K antagonists, a place will remain for "old" anticoagulants during the next years.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Evidence-Based Medicine; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Clinical Trials as Topic; Humans; Morpholines; Practice Guidelines as Topic; Rivaroxaban; South Africa; Thiophenes; Thrombectomy; Venous Thromboembolism

Due to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement.. Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources.. 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%.. Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of 547,422 Euro over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to 270,068 Euro.. According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxis.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Budgets; Cost Control; Dabigatran; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Morpholines; Polysaccharides; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Spain; State Medicine; Thiophenes; Venous Thromboembolism

For decades, parenteral drugs, such as the low molecular weight heparins and unfractionated heparins or vitamin K antagonists, have been used as anticoagulants for prevention of venous thromboembolism following major lower limb surgery. However, these regiments have limitations that rendered the quest for new anticoagulants mandatory. Recently, research has been focused on the development of orally active small molecules that directly target thrombin or activated factor X (FXa). These regiments exhibit a number of characteristics that an "ideal" anticoagulant should possess. Currently, two agents, dabigatran etexilate and rivaroxaban, which inhibit thrombin and FXa, respectively have been approved in the European Union and Canada for venous thromboprophylaxis in patients undergoing elective hip- or knee-replacement surgery. Other agents are at an early or late stage of clinical evaluation. In this study, we summarize the current evidence for these new developed or under development drugs regarding their applications in the filed of lower limb orthopaedic surgery.

Topics: Anticoagulants; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Drugs, Investigational; Factor Xa Inhibitors; Humans; Lower Extremity; Morpholines; Orthopedic Procedures; Pyridines; Rivaroxaban; Thiophenes; Thrombin; Venous Thromboembolism

Four phase III studies compared oral rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA or TKA). A pooled analysis of these studies compared the effect of rivaroxaban with enoxaparin on symptomatic VTE plus all-cause mortality and bleeding events, and determined whether these effects were consistent in patient subgroups. Patients (N=12,729) aged ≥18 years and scheduled for elective THA or TKA received rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily or 30 mg every 12 hours. The composite of symptomatic VTE and all-cause mortality, the prespecified primary efficacy endpoint and adjudicated bleeding events were analysed in the day 12± 2 active treatment pool. Subgroup analyses of these outcomes were performed over the total treatment period. In the day 12± 2 pool, the primary efficacy endpoint occurred in 29/6,183 patients receiving rivaroxaban (0.5%) versus 60/6,200 patients receiving enoxaparin (1.0%; p=0.001). Major bleeding occurred in 21 (0.3%) versus 13(0.2%) patients, p=0.23; major plus non-major clinically relevant bleeding in 176(2.8%) versus 152 (2.5%) patients, p=0.19; and any bleeding in 409 (6.6%) versus 384 (6.2%) patients, p=0.38, respectively. The reduction of symptomatic VTE plus all-cause mortality was consistent across prespecified subgroups (age, gender, body weight, creatinine clearance) in the total treatment period. Compared with enoxaparin regimens, rivaroxaban reduces the composite of symptomatic VTE and all-cause mortality after elective THA or TKA, with a small increase in bleeding, no signs of compromised liver safety and fewer serious adverse events.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials, Phase III as Topic; Double-Blind Method; Enoxaparin; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Morpholines; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Although currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low molecular weight heparin and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa. The new agents produce such a predictable anticoagulant response that they can be given in fixed doses without monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Drug Discovery; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombin; Venous Thromboembolism; Vitamin K

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Drug Interactions; Hemorrhage; Humans; Kidney Diseases; Morpholines; Pyridines; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

To compare the efficacy, in the prevention of venous thromboembolism (VTE), and safety, of rivaroxaban and dabigatran relative to the common comparator enoxaparin.. Two randomized clinical trials of dabigatran, one after total hip replacement (THR), RE-NOVATE, and one after total knee replacement (TKR), RE-MODEL, were identified as using the same enoxaparin regimen (40 mg once daily given the evening before surgery) and being of comparable duration to two rivaroxaban trials, RECORD1 and RECORD3. Indirect comparisons were performed on both efficacy and safety endpoints. To enable comparisons, symptomatic VTE results were based on the total study duration period, i.e. including the follow-up period. Major bleeding included surgical-site bleeding events.. After THR, rivaroxaban 10 mg once daily significantly reduced total VTE and symptomatic VTE relative to dabigatran 220 mg once daily (relative risk 0.34 and 0.19, respectively). After TKR, rivaroxaban significantly reduced total VTE versus dabigatran (relative risk 0.53); symptomatic VTE was not different between dabigatran and rivaroxaban. There was no significant difference in the rates of major bleeding for patients receiving rivaroxaban or dabigatran.. Based on the indirect comparisons, rivaroxaban was estimated to be more efficacious than dabigatran in the prevention of total VTE after THR and TKR. Our analysis relied upon published data for dabigatran and did not have the advantages of more detailed comparative data obtained directly from a randomized trial, as was the case with rivaroxaban. Further comparative research may be of value, but until available our conclusions represent the best available evidence.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Female; Health Care Costs; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Risk; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Health Care Costs; Humans; Morpholines; Rivaroxaban; Thiophenes; United States; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Anticoagulant drugs reduce the risk of venous thromboembolic events after total hip and knee arthroplasty. However, the use of current drugs, such as low-molecular-weight heparins, is hampered by their subcutaneous administration. The use of a vitamin K antagonist, such as warfarin, is hampered by the required routine coagulation monitoring and dose titration to provide effective anticoagulation without an increased risk of bleeding. Numerous possible food and drug interactions must also be considered. New classes of oral anticoagulant agents have been developed that have a fixed dose, do not require coagulation monitoring, do not have food and drug interactions, and demonstrate similar or better efficacy and safety profiles when compared with current agents.

Topics: Anticoagulants; Antithrombin Proteins; Arthroplasty, Replacement, Knee; Benzimidazoles; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Orthopedic Procedures; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Clinical data on the risk factors, incidence, consequences and current treatment options of venous thromboembolism are reviewed. Current guidelines advise anticoagulant treatment for a few weeks or months in immobilized patients treated in hospital, and after major surgery. The initial treatment is based on heparin, followed by vitamin K antagonist treatment. Recently a number of new, partially orally administered medications have undergone clinical investigations and based on the results three of them were also registered for the prevention and treatment of venous thromboembolism. Direct thrombin inhibitors, direct and indirect Factor Xa inhibitors exhibited proven non-inferiority or superiority compared with traditional treatment options. The superior efficacy or non-inferiority was not accompanied with an increase in the bleeding risk. Results of the most important clinical trials are reviewed. Based on these results, prevention and treatment of venous thromboembolism will change substantially in the near future.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Drug Costs; Drugs, Investigational; Factor Xa Inhibitors; Humans; Hungary; Morpholines; Oligosaccharides; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thiophenes; Thrombin; Venous Thromboembolism

It was the objective of this study to quantify the effects of rivaroxaban administration on global coagulation parameters associated with routine clinical procedures, we collected plasma samples from patients undergoing major orthopaedic surgery receiving rivaroxaban at various time points after drug administration. Forty-seven patients received rivaroxaban (10 mg daily) for venous thromboembolism prophylaxis. Blood samples were collected at four different time points: A) before surgery; B) before drug administration at day 4-5 after surgery (steady state of rivaroxaban); C) 2 hours (h) after drug administration and D) 12 h after drug administration. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), antithrombin (AT) level, fibrinogen level by Clauss method (FibC), and derived fibrinogen (dFIB) level were assessed with various reagents. At 2 h after rivaroxaban administration, the PT and aPTT clotting times were significantly prolonged to different extents up to 1.4 fold, whereas 12 h after drug administration, no significant effect was observed. Rivaroxaban administration had no influence on the TT or the FibC concentration. The dFIB assay was differentially affected by rivaroxaban when different reagents were tested. The AT assay dependent on thrombin activity was not influenced by rivaroxaban, whereas the AT levels dependent on factor Xa activity were significantly increased by rivaroxaban. Clinicians should be aware of the time-dependent influence of rivaroxaban on factor Xa-dependent routine coagulation assays. Therefore, routine coagulation parameters should be assessed directly before drug administration to keep the interaction of rivaroxaban low.

Topics: Aged; Anticoagulants; Antithrombins; Blood Coagulation; Blood Coagulation Tests; Clinical Protocols; Drug Interactions; Factor Xa Inhibitors; Female; Fibrinogen; Humans; Male; Middle Aged; Morpholines; Orthopedic Procedures; Postoperative Complications; Rivaroxaban; Thiophenes; Time Factors; Venous Thromboembolism

Vitamin K antagonists (VKA) are the only registered oral anticoagulants for the treatment of venous thromboembolism (VTE). VKA have an unpredictable and highly variable effect on coagulation, with a high risk of under- and over-treatment. Novel anticoagulants, such as dabigatran and rivaroxaban, could be a very welcome replacement for VKA, as they show a predictable anticoagulant effect. Results of several phase II and III studies have shown the efficacy and safety of dabigatran and rivaroxaban in the prophylaxis and treatment of VTE, and for the prevention of stroke in atrial fibrillation. It remains to be shown whether these new anticoagulants have the same safety profile in daily clinical practice, where more vulnerable patients will be treated. Lack of information on the proper monitoring method or antidote in case of bleeding may also hinder the translation from science to clinical practice.

Topics: Acute Coronary Syndrome; Anticoagulants; Arthroplasty, Replacement, Hip; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Diet; Drug Interactions; Factor VIIa; Factor Xa Inhibitors; Humans; Kidney; Life Style; Monitoring, Physiologic; Morpholines; Recombinant Proteins; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

The objective of this study was to evaluate the cost-effectiveness of rivaroxaban versus the low-molecular-weight heparins (LMWH) enoxaparin and dalteparin for the prevention of venous thromboembolism (VTE) after total hip replacement and total knee replacement in Sweden.. The model included acute venous thromboembolic events and long-term complications over a 5-year time horizon represented by an acute and a chronic phase with 1-year cycles. Transition probabilities were derived from the Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism (RECORD) clinical trials.. In patients undergoing total hip replacement, the incremental cost per additional quality-adjusted life-year of extended prophylaxis for 35 days with rivaroxaban versus 14 days of prophylaxis with enoxaparin or dalteparin was SEK29,400 and SEK35,400, respectively. In total knee replacement patients, 14 days of rivaroxaban dominated 14 days of LMWH as prophylaxis for VTE.. The results of the economic model consistently showed that, over a 5-year period, rivaroxaban is a cost-effective alternative to 14 days of LMWH for VTE prophylaxis in Sweden.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Heparin; Humans; Models, Economic; Morpholines; Rivaroxaban; Sweden; Thiophenes; Venous Thromboembolism

The objective of this analysis was the evaluation of the outcomes and costs associated with rivaroxaban and enoxaparin for the prevention of postsurgical venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) and total knee replacement (TKR) from the US payer perspective.. VTE event rates have been reported in three Phase III clinical trials that compared rivaroxaban and enoxaparin for VTE prevention after orthopedic surgery during the prophylaxis (≤35 days for THR patients and 10-14 days for TKR patients) and post-prophylaxis periods (≤90 days following surgery). These data were used in this decision-analytic model to estimate and compare health outcomes and costs associated with rivaroxaban and enoxaparin. The base-case analysis considered the number and costs of symptomatic VTE events during the prophylaxis period only. A 90-day horizon was considered in the sensitivity analysis.. Following THR, when extended durations of prophylaxis (35 days) were compared, rivaroxaban was associated with lower costs than enoxaparin, with total saving costs of $695/patient. When an extended duration of rivaroxaban prophylaxis (35 days) was compared with a short duration (10-14 days) of enoxaparin prophylaxis, rivaroxaban was estimated to prevent 9.9 additional symptomatic VTE events per 1000 patients, while saving $244/patient (rate/1000 patients). In the TKR population, short duration of rivaroxaban prophylaxis was estimated to prevent 13.1 additional symptomatic VTE events per 1000 patients. It was also less costly than short duration enoxaparin prophylaxis, with a saving of $411/patient (rate/1000 patients).. Only statistically significant differences were captured in the base-case economic analysis, and, therefore, differences in pulmonary embolism (PE) and bleeding events were not captured.. In this model, rivaroxaban reduced total treatment payer costs vs enoxaparin for the prevention of VTE in THR or TKR patients.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials, Phase III as Topic; Costs and Cost Analysis; Enoxaparin; Health Services; Humans; Morpholines; Rivaroxaban; Thiophenes; United States; Venous Thromboembolism

Extended thromboprophylaxis is vital in patients undergoing total hip arthroplasty (THA) because of the prolonged risk of venous thromboembolism (VTE). Despite evidence that extended prophylaxis can reduce the incidence of symptomatic VTE in this high-risk patient population and the evidence-based guideline recommendations, a large proportion of patients still do not receive an adequate duration of thromboprophylaxis. This is partly due to the limitations of conventional anticoagulants, such as the subcutaneous route of administration or the requirement for routine coagulation monitoring and dose adjustment. New oral anticoagulants (such as the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitor rivaroxaban) could address the current unmet need. Phase III clinical studies in VTE prevention in patients undergoing THA and total knee arthroplasty (TKA) showed that dabigatran etexilate was non-inferior to the EU regimen of enoxaparin, but did not achieve non-inferiority to the US regimen of enoxaparin. In contrast, rivaroxaban demonstrated superiority to both enoxaparin regimens for the prevention of VTE after THA and TKA, without a significant increase in major bleeding rates. Their convenient, once-daily, fixed dosing, with no need for routine coagulation monitoring, could facilitate adherence to evidence-based guideline recommendations of extended thromboprophylaxis after THA.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Benzimidazoles; Dabigatran; Elective Surgical Procedures; Humans; Morpholines; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) is a common, sometimes even fatal though preventable complication after surgical interventions, especially in orthopaedic surgery. The risk can be reduced by more than 50 % by mechanical means and different anticoagulant drugs. However, only few patients receive adequate treatment. Medicamentous options are limited and somewhat difficult. Most anticoagulant substances act indirectly, therefore their efficacy can easily be impaired. For some, the pharmacokinetics are quite unfavourable. Furthermore, these drugs can cause severe adverse reactions; and since drug therapy either needs daily injections or routine blood checks, its acceptance is limited even further. Fortunately, new substances have reached phase III and will shortly be released. They have a broad therapeutic index, favourable pharmacodynamics and -kinetics and seem to cause only few adverse events. Rivaroxaban, for example, is approved for orthopaedic interventions like total hip or knee replacement. Orally administered, it interacts directly with factor Xa. It proved to be superior compared to the standard therapy with Enoxaparin, has a similar risk profile and needs no routine blood checks. The following article gives a critical survey of the problem, therapeutic options, current guidelines and new possibilities. Hopefully, these new simplified therapy options will increase the acceptance of VTE prophylaxis so that the rate of fatal complications after orthopaedic interventions can further be reduced.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Coagulation Tests; Combined Modality Therapy; Drug Approval; Drug Interactions; Early Ambulation; Enoxaparin; Factor Xa Inhibitors; Humans; Intermittent Pneumatic Compression Devices; Morpholines; Orthopedic Procedures; Postoperative Care; Postoperative Complications; Practice Guidelines as Topic; Rivaroxaban; Stockings, Compression; Thiophenes; Treatment Outcome; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Morpholines; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Topics: Fibrinolytic Agents; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

The peak incidence of venous thrombo-embolism (VTE) occurs 3 weeks following hip arthroplasty surgery and current guidelines proposing VTE prophylaxis continuing for 4 weeks after surgery. This study first compares the duration of treatment and satisfaction between patients prescribed low molecular weight heparin (LMWH) and rivaroxaban, a new oral Factor Xa inhibitor, following elective hip arthroplasty; and second, surveys the duration of LMWH use in other units.. An international survey detailing the use of LMWH was performed. A prospective audit was performed of 100 hip replacements, with 50 prescribed 40 mg once daily of subcutaneous enoxaparin and subsequently 50 patients prescribed 10 mg once daily of oral rivaroxaban. The duration of treatment, patient satisfaction and complications for both cohorts was quantified and compared against published evidence-based guidelines.. The survey demonstrated that four out of 39 (10.2%) units that routinely prescribe LMWH do so for at least 4 weeks following surgery. The audit demonstrated that rivaroxaban afforded a superior mean duration of postoperative VTE prophylaxis (35 days vs 5.4 days; P < 0.05) and superior patient satisfaction. There was no difference in the incidence of bleeding, wound infection or thrombotic complications.. This study demonstrates that patients are exposed to an increased VTE risk following hip replacement surgery due to the inadequate prescription of LMWH. This is poor clinical practice, contrary to current evidence-based guidelines and has potential medicolegal implications. The prescription of rivaroxaban affords a superior patient compliance compared with subcutaneous LMWH, thus ensuring that patients receive VTE prophylaxis for the current recommend period of time.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Drug Administration Schedule; Epidemiologic Methods; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Morpholines; Patient Satisfaction; Postoperative Care; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Clinical Trials as Topic; Cost-Benefit Analysis; Dabigatran; Enoxaparin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Models, Economic; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Quality-Adjusted Life Years; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Apixaban and other factor Xa (FXa) inhibitors are in late-stage clinical development for prevention and treatment of thromboembolic diseases. Although routine monitoring will not be required, in certain situations assessment of drug level may be helpful. This study evaluated the suitability of commercially available prothrombin time/international normalised ratio (PT/INR) and anti-FXa activity assays to measure FXa inhibitors in plasma. Twelve PT (ISI 0.89-1.88) and three anti-Xa assays were evaluated in vitro using human plasma spiked with four FXa inhibitors (0-2,000 ng/ml). Assay variability and correlation with drug plasma exposure were evaluated in patients with venous thromboembolism (VTE) treated with apixaban. All FXa inhibitors prolonged PT; however, assay sensitivity was dependent on thromboplastin reagents used and FXa inhibitors tested. To achieve a doubling of PT, the concentration of each FXa inhibitor varied 2.6- to 8-fold between thromboplastin reagents. The rank order of a FXa inhibitor's effect on PT ratio varied across thromboplastin reagents. Conversion to INR increased variability. Different anti-Xa assays showed different dynamic ranges for each FXa inhibitor; however, their rank order was consistent. For apixaban, the dynamic range of <7.8-240 ng/ml, and inter- and intra-assay precision of <6% coefficient of variation by Rotachrom assay appeared suitable for the anticipated apixaban plasma concentrations with 2.5 and 5 mg bid clinical doses. The stronger correlation between apixaban plasma concentration and anti-Xa activity (r2 = 0.88-0.89) compared with PT/INR (r2 = 0.36) in patients undergoing VTE treatment suggested that anti-Xa activity was the better indicator of apixaban plasma concentrations.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Drug Monitoring; Factor Xa Inhibitors; Humans; International Normalized Ratio; Isoxazoles; Morpholines; Predictive Value of Tests; Prothrombin Time; Pyrazoles; Pyridones; Reproducibility of Results; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Arthroplasty, Replacement, Hip; Drug Administration Schedule; Fibrinolytic Agents; Humans; Morpholines; Postoperative Care; Postoperative Complications; Retrospective Studies; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Clinical Trials as Topic; Dabigatran; Fibrinolytic Agents; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Benzimidazoles; Dabigatran; Enoxaparin; Fibrinolytic Agents; Humans; Morpholines; Pyridines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Topics: Anticoagulants; Cost of Illness; Enoxaparin; Evidence-Based Medicine; Humans; Length of Stay; Morpholines; Orthopedic Procedures; Risk Reduction Behavior; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Drug Interactions; Elective Surgical Procedures; Humans; Morpholines; Netherlands; Patient Selection; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Patients undergoing total hip or knee arthroplasty face an increased risk for venous thromboembolism in the days and weeks following surgery. Hence, the routine application of prophylactic strategies is currently recommended. These include parenteral anticoagulants such as the low-molecular-weight heparins or fondaparinux and oral anticoagulants such as warfarin. New anticoagulant drugs are rapidly becoming available, including drugs that are administered orally, at fixed doses and without laboratory monitoring. Rivaroxaban is the first of a new class of anticoagulants: the selective, direct Factor Xa inhibitors. It has completed clinical evaluation in the setting of major orthopedic surgery and is now approved in many countries for the prevention of venous thromboembolism in patients undergoing total knee and hip arthroplasty. In this paper, we will review the trial data now supporting the clinical use of rivaroxaban and will discuss the potential role of this agent in daily clinical practice.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Design; Factor Xa Inhibitors; Humans; Morpholines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Oral factor Xa (FXa) inhibitors are a promising alternative to current anticoagulants. This paper reviews the latest developments of oral direct FXa inhibitors and focuses on those which have been approved for the prevention of venous thromboembolism (VTE) after total hip or knee replacement or are in advanced development and have passed phase II (proof of principle) testing. The most advanced drugs are apixaban, betrixaban, edoxaban, eribaxaban, rivaroxaban, LY517717, TAK-442, and YM150. Rivaroxaban (Xareltoâ) is the first direct FXa inhibitor which has recently been approved for the prevention of VTE in adult patients after elective hip or knee replacement in several countries, including the European Union and Canada. Rivaroxaban has a flat dose-dependent anticoagulant response with a wide therapeutic window and low potential for drug-drug and drug-food interactions. Rivaroxaban can be given in fixed doses without coagulation monitoring. This review describes the pharmacodynamic and pharmacokinetic profiles and the results of clinical trials with FXa inhibitors in the prevention and treatment of thromboembolic disorders.

Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Glycine; Hemostasis; Humans; Morpholines; Piperazines; Pyrazoles; Pyridones; Pyrrolidines; Rivaroxaban; Thiophenes; Venous Thromboembolism

It has been estimated that major orthopaedic surgery has the highest risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) when compared with other surgery. Two new orally active anticoagulants have recently become licensed in Ireland for the primary prevention of venous thromboembolism in adult patients undergoing elective total hip replacement (THR) or total knee replacement (TKR). Rivaroxaban (Xarelto) is a direct factor Xa inhibitor and dabigatran etexilate (Pradaxa) is a prodrug of the active compound dabigatran, which inhibits thrombin.. To evaluate the cost effectiveness of rivaroxaban and dabigatran etexilate compared with enoxaparin sodium for the prophylaxis of venous thromboembolism in patients undergoing elective THR and TKR in the Irish healthcare setting.. The evaluation was conducted from the Irish health-payer perspective. A static decision-tree model was developed with a 180-day post-surgery time horizon. Separate models for the disease states THR and TKR were run to accommodate the different venous thromboembolism risks associated with each procedure. Outcome measures were QALYs and life-years gained (LYG). Costs were valued in euro, year 2008 values. One-way sensitivity analysis of all probabilities in the model was performed. A probabilistic sensitivity analysis using second-order Monte Carlo simulation was performed to determine the probability of cost effectiveness at euro 45,000 per QALY threshold.. In the THR base-case model, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. The incremental cost-effectiveness ratios for dabigatran etexilate relative to enoxaparin were euro 23,934 per LYG and euro 17,835 per QALY. In the TKR base-case model, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. Dabigatran etexilate also dominated enoxaparin sodium. In the one-way sensitivity analysis, the THR model was robust to all but four probability variations; the TKR model was robust to all variations. At a cost-effectiveness threshold of euro 45,000 per QALY, the probability that rivaroxaban was the most cost-effective strategy after THR was 39%, followed by dabigatran etexilate at 32% and enoxaparin sodium at 29%. The probability that rivaroxaban was the most cost-effective strategy after TKR was 46%, followed by dabigatran etexilate at 30% and enoxaparin sodium at 24%.. Base-case analysis indicates that when both rivaroxaban and dabigatran etexilate are compared with enoxaparin sodium, rivaroxaban is the less costly and more effective option after THR and TKR. Probabilistic sensitivity analysis indicates that rivaroxaban is the most cost-effective strategy at a cost-effectiveness threshold of euro 45,000 per QALY; however, there is uncertainty regarding this strategy being more cost effective than dabigatran etexilate when both are compared with enoxaparin sodium.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Cost-Benefit Analysis; Dabigatran; Decision Trees; Enoxaparin; Fibrinolytic Agents; Humans; Ireland; Models, Economic; Monte Carlo Method; Morpholines; Pyridines; Quality-Adjusted Life Years; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) is a major cause of death in hospitalized patients. In particular, patients undergoing elective major lower-limb orthopaedic surgery are at high risk of developing post-operative VTE. Rivaroxaban, a new oral anticoagulant, has been shown to be more effective than enoxaparin in reducing total and symptomatic VTE with similar major and non-major bleeding rates in patients undergoing elective total hip or total knee replacement.

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Morpholines; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Benzimidazoles; Blood Loss, Surgical; Cesarean Section; Contraindications; Dabigatran; Europe; Evidence-Based Medicine; Female; Fetus; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Morpholines; Polysaccharides; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Pyridines; Rivaroxaban; Societies, Medical; Thiophenes; Thrombophilia; United States; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Benzimidazoles; Dabigatran; Enoxaparin; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Clinical Trials as Topic; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

Most hospitalized patients present risk factors for venous thromboembolism (VTE). Deep vein thrombosis and pulmonary embolism are relevant causes for morbidity and mortality in the perihospital phase, with a possibly fatal outcome. Surgical as well as nonsurgical patients with acute medical illness are at risk and show comparatively high rates of VTE. Because of this, an effective and safe prophylaxis for hospitalized patients is necessary. Definition of different risk categories and treatment of patients according to the individual risk profile is standard in VTE prophylaxis. For VTE prophylaxis various medical and mechanical options are available.

Topics: Anticoagulants; Factor Xa; Humans; Inpatients; Laparoscopy; Morpholines; Reoperation; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Body Weight; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Antidotes; Arthroplasty, Replacement; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Pulmonary Embolism; Risk; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Thromboembolic complications are frequent after orthopaedic surgery of the limbs. Strategies to minimize these complications go from recognize the risk factors of the patient to introduce new antithrombotic drugs, and including general medical care, regional anaesthesia and early mobilization. Based in epidemiological studies, prophylaxis must be extended 4-6 weeks in total hip and knee arthroplasty and in surgery of the hip fracture.

Topics: Anesthesia, Conduction; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Early Ambulation; Enoxaparin; Fibrinolytic Agents; Hip Fractures; Humans; Intraoperative Care; Morpholines; Orthopedics; Postoperative Care; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiophenes; Time Factors; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Azetidines; Benzimidazoles; Benzylamines; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dabigatran; Drug Delivery Systems; Drug Design; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Hemorrhage; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Warfarin