rivaroxaban and Obesity

Obesity is an epidemic with rising prevalence, and obese patients are predisposed to comorbid conditions that increase risk for thromboembolic events. It is critical to identify safe and effective anticoagulation therapy for use in this population. Direct oral anticoagulants (DOACs) are a preferred option for anticoagulation in patients of normal weight due to many benefits and equivalent safety and efficacy to their vitamin K antagonist counterparts. However, the safety and efficacy of DOACs in obese patients is not well understood. This review describes recent studies on the pharmacokinetics, safety and efficacy, and clinical outcomes of the DOACs apixaban, rivaroxaban, edoxaban and dabigatran in obese patient populations. DOACs may be a beneficial alternative to vitamin K antagonist therapy in obese patient populations.. The incidence of obesity within the USA is on the rise, as is that of the medical conditions that often accompany it. These include conditions that can predispose individuals to forming clots in the blood, such as atrial fibrillation, which is a form of an abnormal heartbeat, and nonalcoholic fatty liver disease, which is caused by fat buildup around the liver. Therefore, it is important that we have effective medicines that can prevent clotting in an obese patient population. Direct oral anticoagulants are a new, preferred medication option for this, but it is unclear how safe or effective they are in obese people; there is some concern that because of increased body weight, individuals may not get enough medicine to effectively prevent clots from forming, which would ultimately put them at risk for clotting and serious adverse health outcomes such as stroke. This review describes recent studies on the use of the direct oral anticoagulants apixaban, rivaroxaban, edoxaban and dabigatran in obese patients, and whether they are a safe and effective form of anticoagulation in this population.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Body Mass Index; Body Weight; Dabigatran; Hemorrhage; Humans; Obesity; Pyridones; Rivaroxaban; Stroke; Vitamin K

Cardiovascular disease (CVD) remains the leading cause of death in the USA. Several risk factors have been identified, and obesity has become one of prominent concern. Excessive weight is considered a risk factor for CVD based on evidence linking it to a hypercoagulable state. Considering the prevalence of CVD and obesity in the USA, along with the increased risk for thrombus-related events, anticoagulation plays a significant role in prevention and treatment. Direct oral anticoagulants have taken the place of many traditional anticoagulants. Considering the recently approved indications and continued postmarketing studies conducted with rivaroxaban, this updated review provides data on the overall impact of obesity on this compound. This includes data obtained from both healthy obese volunteers and obese patients with various CVD conditions enrolled in rivaroxaban clinical trials, along with data obtained from postmarketing real-world evidence studies. Assessment of the clinical pharmacology and population pharmacokinetics in obese individuals revealed no clinically relevant effects of increased weight. Additionally, subgroup analyses from each of the pivotal phase III trials supporting the current approved labeling also demonstrated consistent efficacy and safety results in obese patients. Lastly, these findings are further supported by several recent real-world evidence studies assessing the continued effectiveness and safety of rivaroxaban. In conclusion, rivaroxaban's overall pharmacological and clinical profile remained consistent in obese adults when assessed in both drug development and postmarketing studies, supporting the premise that higher weight does not necessitate adjustment in either dose strength or regimen.

Topics: Anticoagulants; Area Under Curve; Body Weight; Cardiovascular Diseases; Humans; Metabolic Clearance Rate; Obesity; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Venous Thrombosis

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

Management of atrial fibrillation (AF) in patients with advanced chronic kidney disease (CKD) poses a complex conundrum because of higher risks for both thromboembolic and bleeding complications compared to the general population. This makes it particularly important for clinicians to carefully weigh the risks versus benefits of anticoagulation therapy to determine the individualized net clinical benefit for every patient. During the past few years, 4 non-vitamin K-dependent oral anticoagulant (NOAC) agents have supplemented warfarin in the therapeutic armamentarium for the prevention of systemic thromboembolism in nonvalvular AF. However, the use of NOACs in CKD specifically mandates a nuanced understanding due to their varying dependence on renal clearance, with resultant safety implications related to either underdosing (thromboembolism) or excessive drug exposure (bleeding). This pragmatic review highlights unique considerations pertaining to accurate estimation and temporal monitoring of kidney function in the context of NOAC use with specific clinical deliberations and variables when determining whether an NOAC is appropriate for a patient with CKD. The dependence of NOACs on renal clearance and several troubling safety signals in the published literature suggest that it is vital for nephrologists to be active members of a multidisciplinary team caring for these high-risk patients with CKD and AF.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cyclophosphamide; Dabigatran; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypertension; Male; Multimorbidity; Obesity; Prognosis; Pyrazoles; Pyridones; Renal Insufficiency, Chronic; Risk Assessment; Rivaroxaban; 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

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

The new oral anticoagulants are now a reality and are available to clinicians. Although a large number of patients have been included in the many clinical trials of these drugs, there is one population that is always underrepresented - called special populations - such as those aged more than 75 years old, the obese, and patients with renal impairment. This review aims to analyze differences in the efficacy and safety in these special populations recruited in the various trials.

Topics: Administration, Oral; Age Factors; Anticoagulants; Benzimidazoles; Contraindications; Dabigatran; Embolism; Humans; Morpholines; Obesity; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Rivaroxaban; Stroke; Thiophenes; Thrombosis

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

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

Direct acting non-Vitamin K antagonist oral anticoagulants (NOAC) are characterized by a fixed dosing regimen. Despite the potential for relative underdosing due to large distribution volumes, dose adjustments for patients with high body mass index (BMI) are not recommended. Since efficacy and safety data in obese patients are scarce, we evaluated the impact of BMI on clinical outcomes in daily care patients treated with NOAC for stroke prevention in atrial fibrillation or venous thromboembolism. Using prospectively collected data from a non-interventional registry, cardiovascular (CV), major bleeding events (MB) and all-cause mortality were evaluated according to BMI classes. All outcome events were centrally adjudicated using standard scientific definitions. Between November 1st 2011 and December 31st 2016, 3432 patients were enrolled into the registry (61.3% rivaroxaban; 20% apixaban; 10.1% dabigatran, 8.6% edoxaban; mean follow-up 998.1 ± 542.9 days; median 1004 days). With increasing BMI (range 13.7-57.2 kg/m

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Body Mass Index; Dabigatran; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Obesity; Prospective Studies; Pyrazoles; Pyridines; Pyridones; Registries; Rivaroxaban; Thiazoles; Thromboembolism; Treatment Outcome; Vitamin K

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

Drug-specific anti-Xa concentrations can be used to assess the presence of drug effects; however, there is inadequate guidance for clinicians on the interpretation and clinical application of these results. The purpose of this study is to review patients' first apixaban and rivaroxaban anti-Xa concentrations to identify indications for monitoring and common therapeutic interventions made based on the results. In addition, we compared bleeding and thrombotic outcomes between the obesity group body mass index ≥40 kg/m 2 and the standard group body mass index 25-39.9 kg/m 2 . A retrospective analysis was conducted at a large academic medical center from January 1, 2020, to December 31, 2020. Primary outcomes were indications for anti-Xa concentrations and interventions on results. A total of 180 patients were included in the analysis, with 119 patients (66%) in the apixaban group and 61 patients (34%) in the rivaroxaban group. The most common indications for anti-Xa concentrations were extreme body weight (23%) and concern for bleeding (22%). About half of the anti-Xa concentrations resulted in therapy changes including holding for procedure, switching to heparin or enoxaparin, holding for an elevated anti-Xa concentration or concern for bleeding, adjusting direct-acting oral anticoagulant dose, or switching to an alternative oral anticoagulant. There were no differences in bleeding complications (5% [2] vs. 16% [14], P = 0.11) or thrombotic complications (8% [3] vs. 9% [8], P = 0.85) between the obesity group and the standard group. Despite the lack of validation of therapeutic ranges for anti-Xa concentrations, this study showed clinical situations where anti-Xa concentration monitoring can be of value.

Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Humans; Obesity; Pyridones; Retrospective Studies; Rivaroxaban

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

Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications.. This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m. A total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups.. In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Topics: Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Humans; Obesity; Polypharmacy; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Obesity, a chronic disease established as a global epidemic by the World Health Organization, is considered a risk factor for atrial fibrillation (AF), the most common sustained cardiac arrhythmia, which has high morbidity and mortality. Although both obesity and AF are diseases associated with negative outcomes, studies have shown the presence of an obesity paradox, in which patients with a high body mass index (BMI) and AF have a better prognosis than patients with a normal BMI. Despite the fact that the mechanisms that lead to this paradox are still uncertain, adequate anticoagulation in obese patients seems to play an important role in reducing adverse events in this group. In this perspective article, the authors discuss the relationship between new oral anticoagulants (NOACs), namely, apixaban, edoxaban and rivaroxaban (factor Xa inhibitors) and dabigatran (direct inhibitor of thrombin), and the obesity paradox, seeking to deepen the understanding of the mechanism that leads to this paradox.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Humans; Obesity; Pyridones; Rivaroxaban; Stroke; Thrombin

Topics: Administration, Oral; Anticoagulants; Embolism; Factor Xa Inhibitors; Humans; Obesity; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

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

To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes.. Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models.. A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09).. In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Embolism; Hemorrhage; Humans; Obesity; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

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

Topics: Anticoagulants; Factor Xa Inhibitors; Humans; Obesity; Registries; Rivaroxaban; United Kingdom; Venous Thromboembolism

Topics: Anticoagulants; Clinical Decision-Making; Factor Xa Inhibitors; Humans; Obesity; Rivaroxaban; Uncertainty

Current evidence indicates that the pharmacokinetic profile of rivaroxaban is not significantly impacted by body weight. However, real-world data are needed to better assess the potential clinical benefits and risks associated with rivaroxaban in non-valvular atrial fibrillation (NVAF) patients with obesity. Thus, our objectives were to assess the real-world effectiveness and safety of rivaroxaban versus warfarin among NVAF patients with obesity in the US nationally representative commercially-insured population.. Health insurance claims data from the IQVIA PharMetrics Plus database (January 2010-September 2019) were used to identify NVAF patients with obesity (based on diagnosis codes) initiated on rivaroxaban or warfarin. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances between groups. Study outcomes of interest were evaluated up to 36 months post-treatment initiation and included the composite of stroke or systemic embolism (stroke/SE) and major bleeding. Outcomes were compared using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CIs).. These results suggest that rivaroxaban is an effective and safe treatment option among NVAF patients with obesity in a commercially-insured US population.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Obesity; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m. We enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs' peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found ​​below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed to identify baseline variables associated with DOACs' plasma concentration out of the expected range.. A total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme obesity (mean [SD] body mass index. 44.43 [3.54] kg/m. Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Humans; Male; Obesity; Rivaroxaban; Stroke

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Body Mass Index; Comorbidity; Factor Xa Inhibitors; Female; Heart Disease Risk Factors; Hemorrhage; Humans; Incidence; Japan; Male; Middle Aged; Myocardial Infarction; Obesity; Product Surveillance, Postmarketing; Prospective Studies; Risk Assessment; Rivaroxaban; Stroke; Thinness; Thromboembolism; Time Factors; Treatment Outcome

There is little evidence to guide the use of direct oral anticoagulants (DOACs) in patients with class III obesity. Clinicians face the dilemma that using DOACs in patients with class III obesity may not provide adequate anticoagulation, while avoiding DOACs may deprive them of a useful therapeutic option. We present 2 cases describing our experience navigating rivaroxaban use in patients with class III obesity and review available case reports of measurement of rivaroxaban levels using a calibrated anti-factor Xa assay.. In patient case 1, the rivaroxaban trough level was within the reference range, and therapy was continued. In patient case 2, the rivaroxaban trough level was below the reference range, and the patient's anticoagulation therapy was switched to warfarin. No thromboembolic events were noted in the 2 patients more than 1 year (15 and 22 months, respectively) after initiation of anticoagulation therapy. Because of the many advantages associated with use of DOACs instead of vitamin K antagonists, further research is critical to enabling clinicians to use DOACs more confidently in a broader population.. When monitoring rivaroxaban therapy in patients with class III obesity, there is uncertainty regarding clinical interpretation of drug levels that fall outside of established reference ranges, and monitoring is not standardized or widely available. In addition to case reports found in the literature, the presented cases highlight these challenges and differing clinical decisions made when evaluating rivaroxaban levels in patients with class III obesity.

Topics: Anticoagulants; Blood Coagulation; Drug Monitoring; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Obesity; Rivaroxaban

Topics: Bariatric Surgery; Female; Humans; Male; Obesity; Rivaroxaban; Thrombin

Topics: Anticoagulants; Carbamazepine; Humans; Obesity; Pulmonary Embolism; Rivaroxaban

Topics: Anticoagulants; Bariatric Surgery; Dabigatran; Factor Xa Inhibitors; Humans; Obesity; Rivaroxaban

To compare the level of adherence of public health nurses to BP measurement guidelines based on their knowledge if the guidelines and skills in BP measurement before and after Blood Pressure Measurement Training Program (BPMTP).. An experimental pre- and post-test design using two-staged cluster randomization was conducted. 118 PHNs (mean age ± 38.45 years, mean years of experience ± 13.45 years; 84.1% women) from six districts in Manila were equally assigned to either the BPMTP group or control group. Structured instruments were used.. This study showed that Blood Pressure Measurement Training Package is feasible in improving adherence of nurses based on their increased knowledge of the BP measurement guidelines and skills in BP measurement. A larger-scale study is warranted to show that BPMTP can potentially improve clinical management of hypertension in public health clinics globally.. The fixed dose of 15 mg rivaroxaban might carry a risk of under exposure, which would lead to an increase of thromboembolic complications in patients with high BMI. Therefore, rivaroxaban dose increase was suggested for obese patients. Use of DOACs appears to have considerable safety in obese patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alzheimer Disease; Angiotensin II; Animals; Antithrombins; Atrial Fibrillation; Body Mass Index; Catheter Ablation; Cohort Studies; Dabigatran; Dogs; Embolism; Factor Xa Inhibitors; Female; Genotype; Hemorrhage; Humans; Hypertension; Hypertrophy, Left Ventricular; Incidence; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Middle Aged; Norepinephrine; Obesity; Polymorphism, Single Nucleotide; Retrospective Studies; Rivaroxaban; Stroke; Sympathectomy

Topics: Aged; Aged, 80 and over; Body Mass Index; Factor Xa Inhibitors; Humans; Laser Therapy; Male; Obesity; Prostatectomy; Prostatic Hyperplasia; Risk Factors; Rivaroxaban; Treatment Outcome

Topics: Atrial Appendage; Atrial Fibrillation; Coronary Thrombosis; Echocardiography, Transesophageal; Factor Xa Inhibitors; Humans; Hypertension; Male; Middle Aged; Obesity; Rivaroxaban

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

New oral anticoagulants, soon available in clinical practice, will deeply change the management of venous thromboembolism. The main advantage of these drugs is the route of administration. Moreover, among the new oral anticoagulants, rivaroxaban has a better efficacy than enoxaparin to prevent thromboembolic events after major orthopaedic surgery (THR and TKR). In phase III studies, safety profile seems adequate. A new era for prophylaxis of VTE is beginning with the new oral anticoagulants. However, improvement in the management of patients with renal failure, obese patients or elderly is needed considering that these patients have a high thrombotic and/or hemorrhagic risk.

Topics: Administration, Oral; Aged; Anticoagulants; Clinical Trials, Phase III as Topic; Comorbidity; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Morpholines; Obesity; Postoperative Complications; Preanesthetic Medication; Rivaroxaban; Thiophenes; Thromboembolism; Thrombophilia; Venous Thrombosis