Rivaroxaban's vascular dose for the neurovascular clinician.

Rivaroxaban, a direct oral anticoagulant, has proven efficacy and safety at its standard dose in the treatment and prevention of various vascular conditions. These include the treatment of venous thromboembolism and stroke prevention in non-valvular atrial fibrillation. A "very low" vascular dose of rivaroxaban, when combined with low-dose aspirin, has been demonstrated to reduce major adverse cardiovascular events, including stroke, in both acute and chronic coronary syndrome. The combination of rivaroxaban and low-dose aspirin could potentially offer an additional strategy for stroke prevention in selected non-atrial fibrillation patients who are at a high risk of stroke.

Effective Non-invasive Treatment of Lingual Hematoma in an End-Stage Renal Disease (ESRD) Patient on Rivaroxaban: A Case Report.

Lingual hematoma is a rare, life-threatening condition that can obstruct the airway. We report a 73-year-old male with end-stage renal disease (ESRD) who developed lingual hematoma while on rivaroxaban. He presented with odynophagia and significant tongue swelling. Treatment with vitamin K, dexamethasone, tranexamic acid, and prothrombin complex concentrate led to rapid improvement without the need for intubation. This case highlights the importance of prompt medical management to prevent airway obstruction in similar patients.

Unveiling May-Thurner Syndrome in a Case of Recurrent Deep Venous Thrombosis With Bilateral Pulmonary Embolism.

May-Thurner syndrome (MTS) is a rare cause of deep venous thrombosis (DVT), characterized by the external compression of the left common iliac vein by the right common iliac artery against bony structures. Risk factors for MTS include female sex (postpartum, multiparous, and using oral contraceptive pills), spinal abnormalities like scoliosis, prior aortoiliac vascular stent placement, dehydration, and hypercoagulability. MTS patients with partial obstruction can be asymptomatic, but progression to extensive symptomatic DVT and/or chronic venous insufficiency can occur. MTS can be diagnosed by non-invasive imaging studies including ultrasound (US), computed tomography (CT) scan, magnetic resonance imaging (MRI), venogram, catheter-based venogram, and intravascular US. For MTS patients with moderate to severe symptoms, we suggest thrombectomy, angioplasty, and stenting of the affected segment. In this case report, we highlight a 44-year-old male with a recent diagnosis of left-sided DVT on apixaban who presented with worsening leg swelling. DVT, pulmonary embolism (PE), and MTS were diagnosed with a lower extremity US, chest CT angiography, and abdominal/pelvic CT scan and venography, respectively. The patient underwent interventional radiology-guided local thrombolysis, thrombectomy, and venoplasty along with stent placement in the left common iliac vein. Subsequently, the patient was discharged on rivaroxaban.

Evaluating Renal Benefits of Rivaroxaban Versus Vitamin K Antagonists in Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Evidence.

Background: AF is a global health concern, with systemic complications including renal dysfunction. This systematic review and meta-analysis compares the effects of rivaroxaban, a Factor Xa inhibitor, and vitamin K antagonists (VKAs) on renal outcomes in AF patients. Methods: The study protocol is registered in PROSPERO (ID: CRD42023462756). We systematically searched the PubMed, Embase and Cochrane Library databases from 1 January 2017 to 30 June 2023 for real-world studies comparing the effects of rivaroxaban and VKAs on renal outcomes in AF patients, including acute kidney injury, a .30% decrease in estimated glomerular filtration rate, doubling of serum creatinine and worsening renal function. Subgroup analyses targeted diabetes, pre-existing kidney disease, the elderly (age .65 years) and Asian populations. The risk of bias was assessed used the Robins-I tool. HRs and 95% CIs were synthesised through a random-effects model. Two sensitivity analyses were performed, using a fixed-effects model and excluding conference abstracts. Results: We identified 1,666 records. After screening, 14 studies comparing rivaroxaban and VKAs were included. Rivaroxaban exhibited superiority over VKAs in preventing: acute kidney injury (HR 0.68; 95% CI [0.61.0.77]; p<0.00001); a .30% decrease in estimated glomerular filtration rate (HR 0.71; 95% CI [0.60.0.84]; p<0.0001); doubling of serum creatinine (HR 0.50; 95% CI [0.36.0.70]; p<0.0001); and worsening renal function (HR 0.56; 95% CI [0.45.0.69]; p<0.00001). Subgroup and sensitivity analyses consistently confirmed rivaroxaban's favourable effects on renal outcomes in diabetes, pre-existing kidney disease, the elderly and Asian populations. Conclusion: Our findings support the preference of rivaroxaban over VKAs for renal outcomes in AF. The findings endorse rivaroxaban as the preferred anticoagulant to mitigate renal complications, offering clinicians valuable insights for tailored strategies.

The development of an innovative method to improve the dissolution performance of rivaroxaban.

Recent advancements in the formulation of solid dosage forms involving active ingredient-cyclodextrin complexes have garnered considerable attention in pharmaceutical research. While previous studies predominantly focused on incorporating these complexes into solid states, issues regarding incomplete inclusion prompted the exploration of novel methods. In this study, we aimed to develop an innovative approach to integrate liquid-state drug-cyclodextrin inclusion complexes into solid dosage forms. Our investigation centered on rivaroxaban, a hydrophobic compound practically insoluble in water, included in hydroxypropyl-ß-cyclodextrin at a 1:1 M ratio, and maintained in a liquid state. To enhance viscosity, hydroxypropyl-cellulose (2 % w/w) was introduced, and the resulting dispersion was sprayed onto the surface of cellulose pellets (CELLETS®780) using a Caleva Mini Coater. The process parameters were meticulously controlled, with atomization air pressure set at 1.1 atm and a fluidizing airflow maintained at 35-45 m3/h. Characterization of the coated cellets, alongside raw materials, was conducted using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. Physicochemical evaluations affirmed the successful incorporation of rivaroxaban into hydroxypropyl-ß-cyclodextrin, with the final cellets demonstrating excellent flowability, compressibility, and adequate hardness. Quantitative analysis via the HPLC-DAD method confirmed a drug loading of 10 mg rivaroxaban/750 mg coated cellets. In vitro dissolution studies were performed in two distinct media: 0.022 M sodium acetate buffer pH 4.5 with 0.2 % sodium dodecyl sulfate (mirroring compendial conditions for 10 mg rivaroxaban tablets), and 0.05 M phosphate buffer pH 6.8 without surfactants, compared to reference capsules and conventional tablet formulations. The experimental capsules exhibited similar release profiles to the commercial product, Xarelto® 10 mg, with enhanced dissolution rates observed within the initial 10 min. This research presents a significant advancement in the development of solid dosage forms incorporating liquid-state drug-cyclodextrin inclusion complexes, offering a promising avenue for improving drug delivery and bioavailability.

Prophylactic dose of rivaroxaban versus warfarin for the treatment of isolated calf muscle vein thrombosis: a retrospective propensity score-matched analysis.

BACKGROUND: Prophylactic dose of rivaroxaban is often used in treatment of isolated calf muscle vein thrombosis (ICMVT), nevertheless, its effect is less reported. This study aims to evaluate short-term outcomes in patients with ICMVT who received prophylactic dose of rivaroxaban or warfarin therapy. METHODS: A retrospective analysis of 472 ICMVT patients who received two different treatment regimens was undertaken. Propensity score matching method was used to balance the confounding effect of baseline clinical data. Chi-squared test and logistic regression analysis were used to compare outcomes (venous thromboembolism events, bleeding events, complete clot resolution) according to the type of treatment regimens before and after propensity score matching. Univariate and multivariable analysis were used to investigate risk factors for incomplete clot resolution of ICMVT after propensity score matching. RESULTS: 242 ICMVT patients received prophylactic dose of rivaroxaban (rivaroxaban group, RG), and 230 received warfarin (warfarin group, WG). After propensity score matching, 156 patients were included in each group; Venous thromboembolism (VTE) events occurred in 14 (9.0%) patients in the RG and 10 (6.4%) in the WG (P = 0.395); No major bleeding events occurred in each group, and clinically relevant non-major bleeding events occurred in 5 (3.2%) patients in the RG and 10 (6.4%) in the WG (P = 0.186); Complete clot resolution at 3 months occurred in 80 (51.3%) patients in the RG and 100 (64.1%) in the WG (P = 0.022). Logistic regression analysis showed that there were no significant differences between RG and WG in VTE events (odds ratio 1.439, 95% confidence interval 0.619 to 3.347, P = 0.397) and clinically relevant non-major bleeding events (odds ratio 0.483, 95% confidence interval 0.161 to 1.449, P = 0.194); it revealed that complete clot resolution rate at 3 months was different in the two groups (odds ratio 0.589, 95% confidence interval 0.375 to 0.928, P = 0.022). Treatment regimens (prophylactic dose of rivaroxaban), thrombosis (maximum diameter >7 mm) and risk factors for VTE (non-surgery risk factors, mainly referring to active malignancy) were risk factors for incomplete clot resolution of ICMVT (P < 0.05). CONCLUSIONS: In this retrospective study with a short-term follow-up, ICMVT patients who received prophylactic dose of rivaroxaban had no significant differences in VTE and bleeding events compared to those who received warfarin therapy (the overall INR > 2.0 for >50% of the time); but it was not conducive to complete clot resolution.

Comparison of warfarin, rivaroxaban, and dabigatran for effectiveness and safety in atrial fibrillation patients with different CHA2DS2-VASc scores: a retrospective cohort study.

BACKGROUND: This retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected. RESULTS: Patients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0-1, 2-3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0-1 (20.0%) than those with score 2-3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0-1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2-3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0-1 and 2-3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy. CONCLUSION: Compared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0-1.

Evaluation of the efficacy and safety of rivaroxaban compared to warfarin in patients with left ventricular apical thrombus: a randomized clinical trial.

INTRODUCTION: This research is one of the pioneering randomized clinical trials (RCTs) aimed at assessing the effectiveness and safety of rivaroxaban in treating left ventricular thrombus (LVT) in patients who have experienced acute coronary syndrome (ACS). MATERIALS AND METHODS: This is a randomized, controlled, interventional, open-label study. The patients were randomly divided into warfarin and rivaroxaban groups. We performed transthoracic echocardiography at the start of the study and again after three months to measure the thrombus area in square millimeters. The morphology of the thrombus was categorized into mural and round, and the mobility was classified into immobile, semi-mobile and hypermobile. We also monitored for adverse events including bleeding, systemic embolic occurrences, rehospitalization, and major adverse cardiac events (MACE). RESULTS: The study included fifty-two patients in the intention-to-treat analysis, with an equal split between the rivaroxaban and warfarin groups (26 patients each). The average follow-up duration was three months. The thrombus resolution rates in the rivaroxaban (76.9%) and warfarin (69.2%) groups, as well as the thrombus size reduction, did not show statistical significance between groups. All semi-mobile or hypermobile thrombi transformed into immobile and all of the round LVTs changed into a mural in both rivaroxaban and warfarin groups. No significant difference was observed in bleeding complications and rehospitalization between the two groups. CONCLUSION: The trial demonstrated that rivaroxaban is as effective as warfarin in terms of thrombus resolution rate, reduction in thrombus size, bleeding risk, and rehospitalization rate. Our findings suggest that rivaroxaban is a viable alternative to warfarin for managing left ventricular thrombus.

Effect of Peripheral Interventions in Patients with Peripheral Artery Disease Receiving Rivaroxaban and Aspirin: Analyses from the XATOA Registry.

OBJECTIVE: To assess the characteristics and clinical outcomes of patients with lower extremity peripheral artery disease (PAD) in XATOA receiving dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin according to lower extremity revascularisation (LER) history. METHODS: XATOA is an international, multicentre, prospective, single arm registry study. This subanalysis investigated patients with lower extremity PAD according to LER history. Patients with coronary artery disease, PAD, or both, receiving DPI were followed for 12 or more months. Baseline characteristics and clinical outcomes were assessed according to LER history. A time dependency analysis assessed outcomes by time between the most recent LER procedure and the start of DPI. A multivariate analysis assessed the influence of patient characteristics on clinical outcomes. RESULTS: In XATOA (n = 5 532), 2 820 (51.0%) patients had lower extremity PAD, of whom 1 736 (61.6%) had prior LER and 1 084 (38.4%) had no prior LER. Baseline characteristics were generally similar between patients with or without prior LER. A higher proportion of patients with prior LER experienced any treatment emergent clinical events compared with those without prior LER (15.0% vs. 9.4%, respectively), with greater differences observed between incidence rates of limb events, including major adverse limb events (9.06 vs. 4.09 events per 100 patient years, respectively). Similar rates of myocardial infarction, stroke, and major bleeding were observed in both subgroups. Clinical event rates were generally higher in patients who had previous LER for six months or less compared with patients who had previous LET for more than six months before starting DPI, regardless of LER type. Multivariate analyses showed that prior LER was predictive of limb events. CONCLUSION: This subanalysis of XATOA found that prior LER was associated with increased rates of limb events, consistent with results of COMPASS and VOYAGER PAD. Rates of bleeding were also low regardless of LER history and consistent with the findings from these trials.

Rivaroxaban and Aspirin in Drug-Coated Balloon Angioplasty for Femoropopliteal In-Stent Restenosis: a retrospective cohort study.

BACKGROUND: After drug-coated balloon (DCB) treatment of the femoropopliteal artery in-stent restenosis (ISR), a certain proportion of patients also experience target lesion restenosis. The purpose of this study was to explore the efficacy and safety of rivaroxaban combined with aspirin in the treatment of ISR after DCB intervention. METHODS: Patients who underwent DCB treatment for ISR after femoropopliteal artery intervention at our center from March 2017 to February 2022 were included consecutively. According to the drug treatment after DCB intervention of ISR, the patients were divided into rivaroxaban and aspirin group (RA Group) and dual antiplatelet therapy (DAPT) group. The outcomes of two groups during the 12-month follow-up after DCB intervention were compared. RESULTS: A total of 92 patients were included in final analysis, with 43 in RA group and 49 in DAPT group. During 12-month follow-up, a total of 15 cases of recurrent ISR were detected, and the recurrence rate of ISR and clinically driven TLR in the RA group were lower than those in the DAPT group (P<0.05). The vascular patency rate in the RA group was higher than that in the DAPT group at 6 and 12 months of follow-up (P<0.05). During the follow-up, there were no adverse events such as death, myocardial infarction, stroke, amputation, or major bleeding, and only a total of 5 cases of minor bleeding occurred. CONCLUSION: Compared with the standard DAPT regimen, rivaroxaban combined with aspirin can safely improve the follow-up outcome after DCB for femoropopliteal ISR.

Effectiveness of Novel Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.

The effectiveness and safety of Rivaroxaban and Edoxaban in the treatment of lower extremity deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) is a medical condition characterized by forming a blood clot, or thrombus, in one of the deep veins, typically in the legs. It is a type of venous thromboembolism (VTE), which refers to the formation of blood clots in the veins. It is caused by Virchow's triad (stasis, hypercoagulation, and endothelial injury). OBJECTIVE: Our main objective is to explore the effectiveness and safety of Rivaroxaban and Edoxaban in treating lower extremity deep vein thrombosis. METHODS: We conducted a retrospective study involving 406 patients subjected to DVT treatment using DOACs (Edoxaban and Rivaroxaban) at our hospital. We recruited adult patients (18 years and above) diagnosed with lower extremity deep vein thrombosis and received treatment with either Rivaroxaban or Edoxaban as the primary anticoagulant therapy for DVT. We excluded patients who received treatment with other anticoagulant medications (warfarin heparin) as the primary therapy for DVT. RESULTS: The groups showed statistically significant differences in red blood cell count and haemoglobin levels, with the Edoxaban group having high values. However, the two groups observed no statistically significant differences in creatinine clearance, white blood cell count, platelet count, C-reactive protein, and D-dimer levels. The difference in the incidence of PE between the two groups was statistically significant (P value < 0.001). The Edoxaban group had fewer PE patients than the rivaroxaban group. The reduction in recurrent thrombosis was significantly higher in the rivaroxaban group compared to the Edoxaban group. There were no significant differences in the major bleeding at various sites across the two treatment groups (p > 0.05). CONCLUSION: Rivaroxaban's pharmacokinetic profile includes rapid absorption and a relatively short half-life. It means that once administered, Rivaroxaban quickly reaches its peak concentration in the blood and is subsequently eliminated from the body within a relatively short period. Edoxaban's pharmacokinetic profile may include slower absorption and a longer half-life than Rivaroxaban. It can result in a slower rate of achieving peak concentration and a more prolonged presence in the bloodstream. These results emphasize the need for careful consideration of anticoagulant therapy in patients with underlying cancer and underscore the importance of managing risks while providing adequate anticoagulation to prevent thrombotic events.

Full Dose Rivaroxaban in Patients with a History of Bariatric Surgery: Bridging the Knowledge Gap through a Phase 1 Study.

BACKGROUND: Bariatric surgery (BS) induces significant changes in gastrointestinal anatomy, potentially influencing the pharmacokinetics of orally administered drugs such as rivaroxaban. OBJECTIVES: This Phase 1 study aimed to assess the pharmacokinetics and safety of full-dose rivaroxaban in post-BS patients. METHODS: The ABSORB study was a single-center, non-randomized, multiple-dose, parallel-design bioequivalence trial. Adult patients with stable weight post Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were compared with subjects with class III obesity and healthy controls. Participants received 20 mg of rivaroxaban daily for 8 days. RESULTS: Post-BS patients exhibited altered rivaroxaban pharmacokinetics, suggesting reduced absorption. Mean AUC0-24h (area under the concentration-time curve from time 0 to 24 hours) after the first dose (RYGB: 1806.8 ng.h/mL; SG: 1648.9 ng.h/mL) was lower compared to controls (1893.5 ng.h/mL). At steady-state (AUCss), AUC values remained lower in BS groups (RYGB: 2129.9 ng.h/mL; SG: 1946.4 ng.h/mL) than controls (2224.8 ng.h/mL). The maximum concentration after the first dose was lower in post-RYGB subjects (214.9 ng/mL) than controls (264.1 ng/mL). This difference was less pronounced at steady-state (RYGB: 256.9 ng/mL vs. controls: 288.8 ng/mL). Neither BS group met bioequivalence criteria compared to controls, whereas the group with class III obesity met bioequivalence criteria compared to controls at steady state. CONCLUSION: Rivaroxaban displayed minor pharmacokinetic variations in post-BS patients. Given reported inter-individual variability in the general population, these variations are unlikely to be of clinical significance. Our findings support rivaroxaban use in BS patients, emphasizing the need for further research in this area.

Prothrombin complex concentrate for emergency surgery in patients on oral Xa-inhibitors.

BACKGROUND: It is uncertain whether prothrombin complex concentrate (PCC) improves hemostasis in patients on treatment with oral factor Xa-inhibitors (XaI) who require emergency surgery. OBJECTIVES: To evaluate whether, in patients with therapeutic levels of oral XaI, preoperative PCC prevents excessive bleeding during and after emergency surgery and is not associated with thrombotic complications. METHODS: We conducted a prospective cohort study wherein a fixed 2000 IU dose of 4-factor PCC was given to patients taking oral XaI with plasma XaI levels of at least 75 ng/mL before the emergency surgery with an expected blood loss of at least 50 mL. Patients were followed for 30 days. The primary efficacy outcome was the incidence of normal or mildly abnormal surgical hemostasis, as assessed by the surgeon; primary safety outcome was the incidence of thromboembolic events within 7 days. RESULTS: We included 20 patients, 50% were female, on apixaban (75%) or rivaroxaban (25%) with median XaI level of 128 ng/mL (range 77-497). The median duration of surgery was 2h 42 min (15 min to 8h 17 min). Normal or mildly abnormal hemostasis was observed in 16 patients (80%), 2 patients had moderately abnormal and 2 had severely abnormal hemostasis, 1 each of those was considered due to local or technical factors. There were 4 deaths (20%) secondary to underlying disease and 1 incidental pulmonary embolism in a patient with cancer. CONCLUSION: A fixed dose PCC appears to control hemostasis in patients with therapeutic plasma levels of apixaban or rivaroxaban requiring emergency surgery.

Results of the COMPASS trial analysed using win ratio compared with conventional analytic approaches.

BACKGROUND: Win ratio (WR) is a newer analytic approach for trials with composite endpoints that accounts for the relative importance of individual components. Our objective was to compare the results of the COMPASS trial analysed using WR compared with conventional statistical approaches. METHODS: We used an unmatched WR analysis for first and total (first plus recurrent) events to examine effects of rivaroxaban plus aspirin and rivaroxaban alone versus aspirin alone on primary efficacy (cardiovascular death, stroke, myocardial infarction), safety (modified International Society on Thrombosis and Haemostasis major bleeding), and net clinical benefit (primary efficacy plus fatal or critical organ bleeding) endpoints. We compared the WR results with those obtained using Cox proportional hazards regression model for first events and Anderson-Gill method for total events. We calculated the win difference to estimate absolute treatment effects. RESULTS: The WR approach produced results consistent with those obtained using conventional statistical methods for the primary composite endpoint (first event: WR 1.32, 95% CI: 1.14 to 1.52; Cox HR 1.32, 95% CI: 1.16 to 1.52; total [first plus recurrent] events: WR 1.32, 95% CI: 1.14 to 1.52; Anderson-Gill HR 1.32, 95% CI: 1.16 to 1.54) as well as for main safety and NCB endpoints. The absolute benefits of the combination of rivaroxaban and aspirin compared with aspirin alone calculated using the win difference were greatest in those with multiple high-risk features. CONCLUSION: Re-analysis of the COMPASS trial results using WR produced results that were consistent with those obtained by conventional statistical approaches.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study.

Introduction: Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Methods: Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. Results: A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. Conclusion: In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.

Cost-Effectiveness and Budget Impact Analysis of Apixaban and Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Non-Valvular Atrial Fibrillation (NVAF) in Iran.

INTRODUCTION: This study evaluates the cost-effectiveness of Apixaban and Rivaroxaban, compared to Warfarin, for stroke prevention in patients with non-valvular atrial fibrillation in Iran. METHOD: A Markov model with a 30-year time horizon was employed to simulate and assess different treatment strategies' cost-effectiveness. The study population comprised Iranian adults with NVAF, identified through specialist consultations, hospital visits, and archival record reviews. Direct medical costs, direct nonmedical, and indirect costs were included. Quality-adjusted life years (QALY) were assessed using an EQ-5D questionnaire. This study utilized a cost-effectiveness threshold of $11 134 per QALY. RESULTS: Apixaban demonstrated superior cost-effectiveness compared to Rivaroxaban and Warfarin. Over 30 years, total costs were lower in the Apixaban and Rivaroxaban groups compared to the Warfarin group ($126.18 and $109.99 vs. $150.49). However, Apixaban showed higher total QALYs gained compared to others (0.134 vs. 0.133 and 0.116). The incremental cost-effectiveness ratio for comparing Apixaban to Warfarin was calculated at -1332.83 cost per QALY, below the threshold of $11 134, indicating Apixaban's cost-effectiveness. Sensitivity analyses confirmed the robustness of the findings, with ICER consistently remaining below the threshold. Over 5 years (2024-2028) of Apixaban usage, the incremental cost starts at USD 70 250 296 in the first year and gradually rises to USD 71 770 662 in the fifth year. DSA and PSA were assessed to prove the robustness of the results. CONCLUSION: This study shows that Apixaban is a cost-effective option for stroke prevention in non-valvular atrial fibrillation patients in Iran compared to Warfarin.

Efficacy and safety of rivaroxaban versus warfarin in the management of unusual site deep vein thrombosis: a retrospective cohort study.

Background: Unusual site deep vein thrombosis (DVT) was defined as venous thromboembolism (VTE) occurring outside the conventional deep veins of the lower extremity or pulmonary arteries. However, the optimal anticoagulation therapy for unusual site DVT remained unclear. This study aims to evaluate the efficacy and safety of rivaroxaban in unusual site DVT. Methods: This retrospective cohort study enrolled consecutive patients at Nanjing Drum Tower Hospital between January 2011 and December 2021 who were diagnosed with unusual site DVT. Patients were divided into two groups based on their ultimate medication choice: the warfarin group and the rivaroxaban group. The demographic characteristics were recorded for all enrolled patients. Clinical outcomes included recurrent VTE, bleeding complications and major bleeding. Results: A total of 1,088 patients were divided into warfarin (n = 514) and rivaroxaban (n = 574) groups. After the stabilized inverse probability of treatment weighting, Hazard Ratios for warfarin vs. rivaroxaban of recurrent VTE, bleeding complications and major bleeding were 0.52(95% CI: 0.25-1.08), 0.30(95% CI: 0.14-0.60), and 0.33 (95% CI, 0.13-0.74), respectively. Risk of clinical outcomes in specified subgroups for age, gender, renal function, thrombosis sites and diagnosis were assessed. The interaction of gender and treatment on major bleeding was significant (P for interaction = 0.062). Otherwise, there was no significant interaction between the other subgroups and the treatment group in terms of clinical outcomes. Conclusion: Compared with warfarin, rivaroxaban exhibited comparable efficacy for the anticoagulant treatment of unusual site DVT, associated with a lower risk of bleeding complications and major bleeding.

Effect of a 3-Month Single-Drug Approach Using Rivaroxaban for Symptomatic Proximal Deep Vein Thrombosis.

Background: Factor Xa inhibitors, such as rivaroxaban, are increasing the convenience of treatment for deep vein thrombosis (DVT). Limited evidence exists regarding clot evaluation at 3 months after treatment for DVT. Methods and Results: We retrospectively analyzed the clinical course of symptomatic proximal DVT in patients who received 3 months of anticoagulation treatment at our hospital. Patients treated with the rivaroxaban single-drug approach were classified as group A (n=42). Patients treated with unfractionated heparin (UFH) or subcutaneous fondaparinux followed by vitamin K antagonist comprised group B (n=60) as an historical cohort. The quantitative ultrasound thrombosis (QUT) score was used to quantify clot burden before and after treatment. No significant differences were observed in patient characteristics between the groups. Serum D-dimer levels in both groups significantly improved after treatment. Clot volume assessed using QUT also reduced significantly in both groups. The QUT score in groups A and B improved from 7.5 [4.8, 12.0] to 3.0 [1.8, 5.0; P=0.000] and 7.0 [4.0, 9.8] to 3.0 [2.0, 5.0; P=0.000], respectively. The change in QUT (∆QUT) was significantly greater in group A compared with group B (-4.5 [-8.25, -2.0] vs. -2.0 [-6.0, 0.0]; P=0.005). Conclusions: We were able to demonstrate the effectiveness of DVT treatment using rivaroxaban over a period of 3 months from onset, in terms of clot regression evaluated using the QUT score.

Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE.

BACKGROUND: Risks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented. METHODS: Subgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6-12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles. RESULTS: 367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding. CONCLUSIONS: Rivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions. TRIAL REGISTRATION: NCT00439725 and NCT02064439.