Anti-Xa Monitoring of Apixaban (ZyQuis) in Venous Thrombo-Embolism and Atrial Fibrillation.

Apixaban is a direct oral Xa inhibitor and is indicated for the treatment of venous thrombo-embolism (VTE) and prevention of stroke in atrial fibrillation (AF). Recently, a generic (ZyQuis, Zydus Lifesciences Limited, India) has received Food and Drug Administration approval. While bioequivalence has been demonstrated with Eliquis (Bristol-Myers Squibb/Pfizer, UK), it is necessary to monitor its effectiveness prior to acceptance in medical practice. This prospective study independently evaluated Apixaban (ZyQuis) at two accredited laboratories. Participants were converted from Warfarin or Rivaroxaban to Apixaban 5 mg bd for a duration of one month. Peak anti-Xa levels were measured 3-4 h post the morning dose. The samples were processed on the Atellica COAG 360 (Siemens Healthineers, Marburg, Germany) analyzers with a chromogenic anti-Xa assay (Innovance, reference interval 69-321 ng/mL). There were 26 participants; 5 men, 21 women; mean ± standard deviation age of 46 ± 12 years. Indications for anticoagulation included: VTE (88.5%) and AF (11.5%). 69.2% of the participants had at least one comorbidity. 96.2% of the anti-Xa levels were within the laboratory's 95% reference interval. Mean anti-Xa activity was 191 ± 69 ng/mL and 186 ± 68 ng/mL measured at respective laboratories. Mean differences in anti-Xa measurements represented by Bland-Altman statistics were small (bias of -2.6%, 95% confidence interval -1.11 to -4.09) and a strong correlation was observed on Deming regression analysis (0.995). Apixaban (ZyQuis) was effective for the management of VTE and AF as evidenced by anti-Xa activity.

Effectiveness and safety of rivaroxaban for anticoagulation therapy in COVID-19: A meta-analysis of randomized controlled trials.

OBJECTIVES: To evaluate the effectiveness and safety of rivaroxaban anticoagulation in COVID-19 patients. METHODS: PubMed, Embase, Cochrane Library electronic databases, and ClinicalTrials.gov were searched to identify all relevant randomized controlled trial studies from December 2019 to July 2023. RESULTS: A total of 6 randomized controlled trials, which included a total of 3323 patients, were considered for evaluation. Overall, short-term all-cause mortality and hospitalization rates were not significantly different between the rivaroxaban and control groups. Thrombotic events were significantly reduced in the rivaroxaban prophylaxis group compared to the placebo control group. However, the reduction in thrombotic events was not significantly different between rivaroxaban therapy and heparin or low-molecular-weight heparin (LMWH). Rivaroxaban prophylaxis and the therapeutic dose may be associated with a higher rate of overall bleeding rate, but major bleeding rates did not differ substantially. CONCLUSION: Rivaroxaban may reduce thrombotic events in COVID-19 patients, but it does not appear to have an advantage over heparin or LMWH, and it may increase the risk of bleeding.INPLASY Reg. No.: INPLASY 202370097.

Use of Andexanet Alfa for Factor Xa Inhibitor Reversal in US Verified Trauma Centers: A National Survey.

Direct oral factor Xa inhibitors are replacing vitamin K-dependent antagonists as anticoagulation treatment in many clinical scenarios. Trauma centers are noting an increase in patients presenting on these medications. The 2018 Food and Drug Administration approval of andexanet alfa provides an alternative anticoagulation reversal. Barriers may limit utilization of new medications including a lack of grade 1A evidence supporting the use of prothrombin complex concentrate (PCC) versus andexanet alfa and cost. To evaluate barriers of andexanet alfa utilization by trauma surgeons, a 15-question survey was conducted. There was a 9% completion rate (n = 89). The results revealed 23.5% would choose andexanet alfa as first-line treatment in children, and 25.8% as first-line treatment in adults. The majority of respondents, 64.7% and 67.4%, would use PCC preferentially in children and adults, respectively. Respondents indicated that cost burden was an overriding factor (76.3%); 42.4% cited lack of high-level efficacy data of andexanet alfa for reversal of factor Xa inhibitors. Additional double-blinded multi-institutional randomized controlled trials comparing 4F-PCC and andexanet alfa for factor Xa inhibitor reversal are needed to support efficacy especially with the increased cost associated.

[Venous thromboembolism - was is new in the revised AWMF guideline?] / Venöse Thromboembolie ­ was ist neu in der aktualisierten AWMF-Leitlinie?

For the diagnosis of a lower-extremity deep vein thrombosis (LEDVT), venous duplex ultrasound is the method of first choice. If a qualified ultrasonography is not timely available, D-dimer testing, and limited ultrasound protocols (point-of-care ultrasound, POCUS) can contribute to therapeutic decision-making when clinical probability is low. A DOAC-based treatment regimen is preferable to a vitamin K antagonist for both acute therapy and secondary prophylaxis of venous thromboembolism (VTE). Treatment with DOACs is unproblematic up to a body weight (BW) of 120 kg or a body mass index (BMI) of 40 kg/m². Weight restrictions are no longer recommended for apixaban and rivaroxaban, but determination of DOAC trough and peak levels is recommended in the extremely obese and patients after bariatric surgery. In cancer-associated VTE, the direct factor Xa inhibitors are a good and safe alternative to low-molecular weight heparins (LMWH) for many patients; the adherence to oral therapy is also higher. Meaningful initial documentation and structured follow-up after LEDVT and pulmonary embolism (PE) are important in order to make an individualized risk-benefit assessment at the end of the therapy phase with regard to continued pharmacological secondary prophylaxis and to reassess patients' symptoms indicating post-thrombotic syndrome (PTS) or chronic thromboembolic pulmonary hypertension (CTEPH).

Patterns of atrial fibrillation anticoagulation with rivaroxaban - 7-year follow-up from the Dresden NOAC registry.

INTRODUCTION: Data on long-term effectiveness and safety of rivaroxaban for stroke prevention in atrial fibrillation (SPAF) are scarce and not available from randomized clinical trials. METHODS: We used data from the prospective, non-interventional DRESDEN NOAC REGISTRY to evaluate rates of stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and ISTH major bleeding, in general and changes of event patterns over time. RESULTS: Between 1st October 2011 and 31st December 2022, 1204 SPAF patients receiving rivaroxaban were followed for 6.7 ± 3.4 years with a mean rivaroxaban exposure of 4.9 ± 3.5 years. During follow up, intention-to treat rates of stroke/TIA/SE were 3.5/100 pt. years (95 % CI 2.5-4.7) in the first year and fell to 1.6/100 pt. years (95 % CI 1.2-2.0) in years 2-5 and 2.1/100 pt. years (95 % CI 1.6-2.7) after 5 years. Similarly, on-treatment event rates fell from 2.4/100 pt. years (95 % CI 1.5-3.5) to 1.1 (95 % CI 0.7-1.5) and 1.6 (95 % CI 1.0-2.3), respectively. Major bleeding rates on treatment were 3.5/100 pt. years in the first treatment year (95 % CI 2.5-4.8) and 2.7 (95 % CI 2.2-3.4) and 3.5 (95 % CI 2.7-4.6) in the periods 2-5 and > 5 years, respectively. Of note, rates of fatal bleeding were low throughout follow-up (0.2 vs. 0.2 vs. 0.1/100 pt. years). CONCLUSIONS: Our results demonstrate the long-term effectiveness and safety of rivaroxaban therapy in unselected SPAF patients in daily care. Our data indicate that patterns of cardiovascular events remain constant over many years. In contrast, bleeding patterns change over time, possibly due to effects of co-morbidities in an ageing population.

Incorporating Prior Data in Quantitative Benefit-Risk Assessments: Case Study of a Bayesian Method.

BACKGROUND: Multiple criteria decision analysis (MCDA) and stochastic multi-criteria acceptability analysis (SMAA) in their current implementation cannot incorporate prior or external information on benefits and risks. We demonstrate how to incorporate prior data using a Bayesian mixture model approach while conducting quantitative benefit-risk assessments (qBRA) for medical products. METHODS: We implemented MCDA and SMAA in a Bayesian framework. To incorporate information from a prior study, we use mixture priors on each benefit and risk attribute that mixes information from a previous study with a vague prior distribution. The degree of borrowing is varied using a mixing proportion parameter. RESULTS: A demonstration case study for qBRA using the supplementary New Drug Application (sNDA) filing for Rivaroxaban for the indication of reduction in the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD) was used to illustrate the method. Net utility scores, obtained from the randomized controlled trial data to support the sNDA, from the MCDA for Rivaraxoban and comparator were 0.48 and 0.56, respectively, with Rivaroxaban being the preferred alternative only 33% of the time. We show that with only 30% borrowing from a previous RCT, the MCDA and SMAA results are favorable for Rivaroxaban, accounting for the seemingly aberrant results on all-cause death in the trial data used to support the sNDA. CONCLUSION: Our method to formally incorporate prior data in MCDA and SMAA is easy to use and interpret. Software in the form of an RShiny App is available here: https://sai-dharmarajan.shinyapps.io/BayesianMCDA_SMAA/ .

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Significant Tricuspid Regurgitation.

BACKGROUND: There are limited data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation with significant tricuspid regurgitation (TR), which can lead to hepatic dysfunction and intestinal malabsorption. We aimed to compare the efficacy and safety of DOACs and warfarin for patients with atrial fibrillation with significant (moderate to severe) TR. METHODS AND RESULTS: A total of 1215 patients with significant TR and atrial fibrillation who were treated with warfarin (N=491) or DOACs (N=724) were retrospectively analyzed. The primary outcomes were ischemic stroke, systemic embolic events, and hospitalization for major bleeding. The secondary outcomes were intracranial hemorrhage, hospitalization for gastrointestinal bleeding, all-cause mortality, and a composite outcome. The median follow-up duration was 2.4 years. In the inverse probability treatment weighting-adjusted cohort, DOACs and warfarin had a similar risk for ischemic stroke and systemic embolic events (adjusted hazard ratio [aHR], 0.95 [95% CI, 0.67-1.36]; P=0.79) and major bleeding (aHR, 0.78 [95% CI, 0.57-1.06]; P=0.11). For the secondary outcomes, relative to warfarin, DOACs had a lower risk of intracranial hemorrhage and the composite outcome, and a comparable risk for gastrointestinal bleeding and all-cause mortality. In the subgroup analysis, the effects of DOACs on ischemic stroke and systemic embolic events were comparable to the effects of warfarin, even in patients with inferior vena cava plethora (increased right atrial pressure) or severe TR. CONCLUSIONS: In this study, relative to warfarin, DOACs demonstrated comparable efficacy for ischemic stroke and systemic embolic events and major bleeding, with a lower intracranial hemorrhage risk in patients with significant TR and atrial fibrillation, indicating their effectiveness and safety.

Four-factor prothrombin complex concentrate versus andexanet alfa for the reversal of traumatic brain injuries.

BACKGROUND: Andexanet alfa was approved in 2018 for reversal of direct oral anticoagulants but due to issues of cost and access, four-factor prothrombin complex concentrate (4F-PCC) continues to be used for this indication. The objective of this study is to evaluate outcomes of reversal with these agents in patients with isolated traumatic brain injuries (TBI). METHODS: This is a retrospective review of 35 trauma centres from 2014 to 2021. Patients were included with an Abbreviated Injury Scale (AIS)>2 for head and having received andexanet alfa or 4F-PCC within 24 hours of admission. Patients were excluded if P2Y12 inhibitor use or AIS>2 outside of head. Primary outcome includes rate of mortality/hospice at hospital discharge. Secondary outcomes include a composite of serious hospital complications. A subgroup analysis of severe TBI patients (AIS head 4 or 5) was completed. Multivariable logistic regression was used to account for differences in comorbidities and TBI severity. RESULTS: 4F-PCC was given to 265 patients with another 59 receiving andexanet alfa. Patients in the andexanet alfa group were more likely to have an AIS head score of 5 (47.5% vs 26.1%; p<0.005). After adjusting for severity of TBI and comorbidities with regard to tomortality/hospice, there were 15 (25.4%) patients in the andexanet alfa group and 49 (18.5%) in the 4F-PCC group (OR 1.34; 95% CI 0.67 to 2.71). This remained consistent when looking at severe patients with TBI with 12 (28.6%) andexanet alfa patients and 37 (28.7%) 4F-PCC patients (OR 0.93 (95% CI 0.40 to 2.16)). Severe hospital complications were also similar between groups with 5 (8.5%) andexanet alfa patients as compared with 21 (7.9%) 4F-PCC patients (OR 1.01; 95% CI 0.36 to 2.88). CONCLUSION: There was no firm conclusion on the treatment effect in mortality/hospice or serious complications among isolated TBI patients reversed with 4F-PCC as compared with andexanet alfa.

Comparison of the Correlation Between Coagulation Indices and Rivaroxaban Concentrations.

BACKGROUND: Rivaroxaban has predictable pharmacokinetics and pharmacodynamics. However, monitoring rivaroxaban concentrations should be provided for special patients with hepatic insufficiency, high bleeding risk, and high thrombotic risk. OBJECTIVE: This study aimed to correlate chromogenic anti-Xa assay, prothrombin time (PT), activated partial thromboplastin time (APTT), thromboelastogram reaction time (TEG R-time), and rivaroxaban concentration measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) (MS-Riva). METHODS: Peripheral venous blood was collected from recruited patients 30 minutes before and 2 to 4 hours after drug administration. High-performance liquid chromatography-tandem mass spectrometry and chromogenic anti-Xa assay measured rivaroxaban concentration. Different assays were compared by Pearson correlation coefficient and Bland-Altman analysis. RESULTS: A total of 104 patients with 191 plasma were included in the study. Overall analysis shows that chromogenic anti-Xa assay, PT, APTT, and TEG R-time strongly correlated with MS-Riva (r = 0.986; r = 0.884; r = 0.741; r = 0.739; P < 0.001). Rivaroxaban peak concentration detected by HPLC-MS/MS (MS-peak) showed a very strong correlation with the chromogenic anti-Xa assay (r = 0.977, P < 0.001) and moderate correlation with PT, APTT, and TEG R-time (r = 0.670; r = 0.571; r = 0.481, P < 0.001). Rivaroxaban trough concentration detected by HPLC-MS/MS (MS-trough) correlated strongly with the chromogenic anti-Xa assay (r = 0.884, P < 0.001), weakly with APTT (r = 0.313; P = 0.043), and not significantly with PT and TEG R-time (P = 0.140; P = 0.341). CONCLUSION AND RELEVANCE: High-performance liquid chromatography-tandem mass spectrometry/MS is the preferred choice for monitoring peak and tough concentrations, followed by anti-Xa, while PT is only suitable for peak concentrations. This study can help the clinicians to better adjust the medication regimen and reduce the risk of recurrence of thrombosis as well as the risk of bleeding.

Use of apixaban in children awaiting heart transplantation.

BACKGROUND: The use of apixaban in the pediatric cardiac population is expanding. We describe our apixaban dosing and monitoring strategy in children and young adults awaiting heart transplantation, along with outcomes related to bleeding and thrombosis during wait-list and early post-transplant periods. METHODS: This study is a retrospective, single-center analysis of all patients receiving apixaban while awaiting cardiac transplantation. Weight-based dosing was monitored with peak drug-specific anti-Xa chromogenic analysis. Significant post-operative bleeding defined by chest tube output or need for surgical intervention. RESULTS: From September 2020 to December 2022, 19 patients, median age 13.5 years (6.1, 15.8 years), weighing 48.9 kg (15.4, 67.6) received apixaban while awaiting transplant. Indication for apixaban was prophylaxis (n = 18, 3 with ventricular assist devices) and treatment of thrombus (n = 1). There were no clinically relevant non-major or major bleeding, nor thrombotic events while awaiting transplant. The median time from last apixaban dose to arrival in the operating room was 23.2 h (15.6-33.8), with median random apixaban level of 37 ng/mL (28.3, 59), 6.3 h (4.8, 8.4) prior to arrival in the operating room. In this study, 32% of patients had significant post-operative bleeding based on chest tube output post-transplant or need for intervention. No patients meeting criteria for significant post-operative bleeding were thought to be attributable to apixaban. CONCLUSIONS: Careful use of apixaban can be safe and effective while awaiting heart transplant. There was no appreciable increase in peri-operative bleeding. The use of apixaban is promising in providing safe, predictable and efficacious anticoagulation while avoiding additional patient stressors.

Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

An extension of biorelevant fed-state dissolution tests to clinical pharmacokinetics - A study on gastrointestinal factors influencing rivaroxaban exposure and efficacy in atrial fibrillation patients.

A direct oral anticoagulant rivaroxaban fails to prevent stroke and systemic embolism in one-to-several percent of patients with nonvalvular atrial fibrillation (NVAF), but the reasons are unknown. The study used semi-mechanistic in vitro-in vivo prediction (IVIVP) modeling to explore the reasons for ineffective thrombosis prevention in NVAF patients. Steady-state drug concentrations in plasma were measured at 0 h (Ctrough), 3 h (C3h), and 12 h post-dosing in thirty-four patients treated with 20 mg rivaroxaban daily. The clinical data were compared against "virtual twins" generated with a novel IVIVP model that combined drug dissolution modeling, mechanistic description of gastric drug transit, and population pharmacokinetics defining the variability of drug disposition. The nonresponders had significantly lower C3h and Ctrough than the responders (p < 0.001) and the covariates included in the population pharmacokinetic submodel did not fully explain this difference. Simulations involving varied gastrointestinal parameters in the "virtual twins" revealed that lower small intestinal effective permeability (Peff), rather than a slower stomach emptying rate, could explain low rivaroxaban exposure in the nonresponders. IVIVP modeling was effectively used for exploring pharmacotherapy failure. Low Peff, found as a major determinant of ineffective rivaroxaban treatment, encourages further research to find (pato)physiological factors influencing suboptimal absorption.

Dose-Related Effectiveness of Andexanet Alfa for Reversal of Apixaban Anticoagulation in a Porcine Polytrauma Model.

BACKGROUND: Andexanet alfa (andexanet) is a reversal agent for use in patients with life-threatening or uncontrolled bleeding treated with oral factor Xa (FXa) inhibitors. There are limited data on the dose-response relationship of andexanet and FXa inhibitor-related bleeding. OBJECTIVE: The aim of this study was to assess the dose-related effectiveness of andexanet in reducing blood loss, improving survival, and reversing apixaban anticoagulation in a porcine polytrauma model. METHODS: Apixaban was given orally to 40 male pigs for 3 days at a dose of 20 mg/d. On day 3, following bilateral femur fractures and blunt liver injury, animals (n = 8/group) received andexanet (250-mg bolus, 250-mg bolus + 300-mg 2-hour infusion, 500-mg bolus, or 500-mg bolus + 600-mg 2-hour infusion) or vehicle (control). Total blood loss was the primary endpoint. Coagulation parameters were assessed for 300 minutes or until death. Data were analyzed with a mixed-model analysis of variance. RESULTS: Administration of 250-mg bolus + 300-mg infusion, andexanet 500-mg bolus, and 500-mg bolus + 600-mg infusion significantly decreased total blood loss by 37, 58, and 61%, respectively (all p < 0.0001), with 100% survival. Andexanet 250-mg bolus was ineffective in reducing total blood loss (6%) and mortality (63% survival) versus controls. Andexanet 500-mg bolus ± infusion neutralized anti-FXa activity to less than 50 ng/mL. Andexanet neutralization of thrombin generation and thromboelastometry parameters was dose and infusion time dependent. CONCLUSION: In a porcine polytrauma model with major bleeding on apixaban, andexanet dose dependently decreased anti-FXa activity. Lower anti-FXa levels (<50 ng/mL) with andexanet 500-mg bolus ± infusion were correlated with 60% less blood loss and 100% survival versus controls.

Real life results of direct-acting oral anticoagulants recommended-dose in obese vs normal-weight patients with venous thromboembolism.

BACKGROUND: There is scarce evidence on the effectiveness and safety of recommended-dose direct acting oral anticoagulants (DOACs) in obese patients with venous thromboembolism (VTE). MATERIAL AND METHODS: We used the data in the RIETE registry to compare the rates of VTE recurrences and major bleeding during long-term therapy with DOACs at recommended doses in patients with body mass index ≥30 kg/m2 (obese) vs. those with BMI 18.5-24.9 kg/m2 (normal weight). We performed regression models with competing risks for death. RESULTS: From January 2013 through October 2022, 2885 obese patients and 2676 with normal weight in RIETE received rivaroxaban (n = 3020), apixaban (n = 1754), edoxaban (n = 636) or dabigatran (n = 151). Median age was 63 years and 52 % were female. At baseline, obese patients were more likely to have diabetes (18.6 % vs. 8.4 %), hypertension (51.9 % vs. 31.4 %) or pulmonary embolism (67.7 % vs. 61 %), and less likely to have renal insufficiency (5.3 % vs. 16 %) or anaemia (21.8 % vs. 28 %%). During anticoagulation (median, 147 vs. 101 days), the obese had a similar rate of VTE recurrences (1.71 vs. 2.14 events per 100 patients-years; hazard ratio (HR): 0.81; 95 % CI: 0.49-1.34) or major bleeding (1.45 vs. 1.76 per 100 patients-years; HR: 0.91; 95 % CI: 0.52-1.59) than those with normal weight. These findings persisted after multivariable analysis (recurrent VTE, HR: 0.80; 95 % CI: 0.48-1.32; major bleeding, HR: 1.11; 95 % CI: 0.60-2.07). CONCLUSION: The use of DOACs at recommended doses in obese patients with VTE was associated with similar rates of VTE recurrences or major bleeding than in patients with normal weight.