Chronic Limb-Threatening Ischemia ; Factor Xa Inhibitors/adverse effects* ; Humans ; Platelet Aggregation Inhibitors/adverse effects* ; Rivaroxaban/adverse effects* ; Singapore ; Treatment Outcome

Objective: This analysis was performed to evaluate the efficacy and the safety of rivaroxaban-aspirin combination therapy in secondary prevention of major adverse cardiovascular events in Chinese patients enrolled in the COMPASS trial. Methods: COMPASS was a prospective, international multi-center and randomized controlled trial. From September 2014 to February 2017, 1 086 patients with stable coronary artery disease and peripheral artery diseases were recruited from 31 centers in China. Patients were randomly assigned to separately receive the therapy of rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day,) group (n=366), rivaroxaban (5 mg twice a day) alone group (n=365), and aspirin (100 mg once a day) alone group (n=355). Baseline information such as age, sex, etc. of all three groups was collected. Finally, 1 081 patients were followed up successfully, with the follow-up rate 99.5% and the average follow-up time was 19 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction and stroke. The primary safety endpoint was major bleeding evaluated by modified International Society on Thrombosis and Haemostasis criteria. Results: Age of patients was (64.2±8.3) years and there were 293 male in rivaroxaban plus aspirin group. Age of patients was (63.8±9.0) years, and there were 301 male patients in rivaroxaban alone group. Age of patients was (63.6±8.8) years, and there were 282 male patients in the aspirin alone group. The incidences of primary efficacy endpoint occurred in 9 cases (1.5%) in rivaroxaban with aspirin group, 21 cases (3.7%) in rivaroxaban alone group and 14 cases (2.5%) in aspirin alone group. Meanwhile, the incidences of primary safety endpoint occurred in 6 cases (1.0%) in rivaroxaban with aspirin group, 9 cases (1.6%) in rivaroxaban alone group and 7 cases (1.2%) in aspirin alone group. The net clinical benefit events were 10 cases (1.7%) in rivaroxaban with aspirin group, 22 cases (3.9%) in rivaroxaban alone group and 15 cases (2.7%) in aspirin alone group (P>0.5%). Conclusions: The combination of rivaroxaban with aspirin can be safe and effectively used for the secondary prevention in Chinese patients with stable coronary artery disease and peripheral artery diseases.
Aged ; Aspirin/therapeutic use* ; Cardiovascular Diseases/prevention & control* ; China ; Drug Therapy, Combination ; Factor Xa Inhibitors/therapeutic use* ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/therapeutic use* ; Prospective Studies ; Rivaroxaban/therapeutic use* ; Secondary Prevention

Apixaban, an inhibitor of direct factor Xa, is used for the treatment of venous thromboembolic events or prevention of stroke. Unlike many other anticoagulant agents, it does not need periodic monitoring. However, monitoring is still required to determine the risk of bleeding due to overdose or surgery. Usually, apixaban concentrations are indirectly quantified using an anti-factor Xa assay. However, this method has a relatively narrow analytical concentration range, poor selectivity, and requires an external calibrator. Therefore, the goal of current study was to establish an analytical method for determining plasma levels of apixaban using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). To this end, apixaban was separated using 2.5 mM ammonium formate (pH 3.0) (A) and 100% methanol containing 0.1% formic acid (B) using the gradient method with a Thermo hypersil GOLD column. The mass detector condition was optimized using the electrospray ionization (ESI) positive mode for apixaban quantification. The developed method showed sufficient linearity (coefficient of determination [r² ≥ 0.997]) at calibration curve ranges. The percentage (%) changes in accuracy, precision, and all stability tests were within 15% of the nominal concentration. Apixaban concentration in plasma from healthy volunteers was quantified using the developed method. The mean maximum plasma concentration (C(max)) was 371.57 ng/mL, and the median time to achieve the C(max) (T(max)) was 4 h after administration of 10 mg apixaban alone. Although the results showed low extraction efficiency (~16%), the reproducibility (% change was within 15% of nominal concentration) was reliable. Therefore, the developed method could be used for clinical pharmacokinetic studies.
Ammonium Compounds ; Anticoagulants ; Calibration ; Chromatography, Liquid ; Factor Xa ; Healthy Volunteers ; Hemorrhage ; Humans ; Mass Spectrometry ; Methanol ; Methods ; Plasma ; Stroke ; Tandem Mass Spectrometry

Rivaroxaban, a factor Xa inhibitor, is one of the newly developed direct oral anticoagulants (DOAC). In recent times, it has been increasingly used in the prevention of pulmonary embolism in patients undergoing orthopedic surgery. This report describes a case of epidural hematoma in an elderly patient who underwent combined spinal epidural anesthesia for total knee arthroplasty; the patient received rivaroxaban postoperatively for 7 days to prevent pulmonary embolism. Additionally, the epidural hematomas developed on the 5th postoperative day but the patient recovered well with conservative treatment. Although rivaroxaban has a low need for monitoring and is easily administered, the guidelines should be carefully checked for the postoperative administration schedule in patients undergoing regional anesthesia. In addition, rivaroxaban should be used with caution, especially in elderly patients.
Aged ; Anesthesia, Conduction ; Anesthesia, Epidural ; Anticoagulants ; Appointments and Schedules ; Arthroplasty, Replacement, Knee* ; Factor Xa ; Hematoma* ; Hematoma, Epidural, Spinal ; Humans ; Orthopedics ; Pulmonary Embolism ; Rivaroxaban*

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031–3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.
Colorectal Neoplasms ; Drug Therapy ; Factor Xa Inhibitors ; Gastrointestinal Tract ; Hemorrhage ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Mortality ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Rivaroxaban ; Stomach Neoplasms ; Venous Thromboembolism

Anticoagulant-related nephropathy (ARN) was initially described in patients on warfarin (as warfarin-related nephropathy) and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis). Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI). A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts. Only one out of 68 glomeruli with open capillary loops had small segmental cellular crescent. Therefore, there was major discrepancy between the degree of glomerular injury and the glomerular hematuria. Considering that the onset of this AKI was associated with apixaban treatment initiation, we propose that this patient had ARN associated with factor Xa inhibitor (apixaban), which has not previously been described. Monitoring of kidney function is recommended after initiation of anticoagulant therapy.
Acute Kidney Injury* ; Biopsy ; Capillaries ; Dabigatran ; Erythrocytes ; Factor Xa ; Hematuria ; Humans ; Kidney ; Necrosis ; Warfarin

Regulatory approvals of non-vitamin K antagonist oral anticoagulants (NOACs) have been based on large randomized phase III trials evaluating dabigatran, rivaroxaban, apixaban, or edoxaban relative to warfarin for atrial fibrillation (AF). The results of the trials showed that all NOACs were at least non-inferior to warfarin in the prevention of stroke/thromboembolism and showed lower rates of intracranial bleeding than those associated with warfarin. However, the trials were designed differently, varied in the inclusion/exclusion criteria, and used either one dose or a low/high dose of the NOAC drug. Some of these differences have challenged the ability to directly compare various NOACs, and comparative data on effectiveness and intracranial bleeding are sparse in “real-world” patients. Real-world data complement data from large randomized phase III trials by providing new aspects of the “real-world” absolute risks of ischemic and hemorrhagic stroke associated with NOACs vs. warfarin. Moreover, “real-world” fragile patients might have been included (e.g., patients with increased risk of bleeding, liver disease, and chronic kidney disease), although these patients would be less represented in trials. This paper introduces recently published real-world data of NOACs and further suggests the recommended dosage of NOACs for Korean patients.
Anticoagulants* ; Atrial Fibrillation ; Complement System Proteins ; Dabigatran ; Factor Xa Inhibitors ; Hemorrhage ; Humans ; Kidney ; Liver Diseases ; Rivaroxaban ; Stroke ; Warfarin

Anticoagulant agents are used to reduce the risk of thromboembolic complications in patients with atrial fibrillation or deep vein thrombosis. Several new generation of oral anticoagulants have been approved. These novel oral anticoagulants (NOACs) include direct thrombin inhibitors, dabigatra etexilate, and the direct factor Xa inhibitors, rivaroxaban, apixaban and edoxaban. This review evaluates NOACs-related gastrointestinal bleeding and summarizes the ideal management strategies based on the guideline suggested by American Society for Gastrointestinal Endoscopy.
Anticoagulants* ; Antithrombins ; Atrial Fibrillation ; Endoscopy ; Endoscopy, Gastrointestinal ; Factor Xa Inhibitors ; Gastrointestinal Hemorrhage ; Hemorrhage ; Humans ; Rivaroxaban ; Thromboembolism ; Venous Thrombosis

For the last half century, vitamin K antagonists (VKAs) have been used for treatment and prevention of venous thromboembolism and stroke prevention in patients with atrial fibrillation. However, their fragile pharmacokinetics, need for routine laboratory monitoring and dose adjustments complicated the use of these drugs. Recently, new oral anticoagulants (NOACs) have overcome the limitation of VKA therapy and shows favorable outcomes and better safety, especially for patients with intracranial hemorrhage, both in phase III clinical trials and real-world registry. Currently available NOACs are one thrombin inhibitor, dabigatran, and three Xa inhibitors, rivaroxaban, apixaban, and edoxaban. This review covers the pharmacokinetics, published pivotal clinical trials, and dose adjustments in chronic kidney disease. The reimbursement criteria, discontinuation during elective surgical procedure, issues on reversal agents are also discussed.
Anticoagulants* ; Atrial Fibrillation ; Dabigatran ; Elective Surgical Procedures ; Factor Xa ; Humans ; Intracranial Hemorrhages ; Pharmacokinetics ; Renal Insufficiency, Chronic ; Rivaroxaban ; Stroke ; Thrombin ; Venous Thromboembolism ; Vitamin K

INTRODUCTIONThis study aimed to compare medication adherence and treatment persistence of patients on warfarin versus rivaroxaban in Singapore. A secondary objective was to identify significant covariates influencing adherence.

MATERIALS AND METHODSA retrospective cohort study was conducted where data from September 2009 to October 2014 was retrieved from the hospital electronic databases. Prescription records of rivaroxaban patients with 3 months or more of continuous prescription were extracted and compared against those of patients on warfarin. Primary outcome of adherence was determined based on the medication possession ratio (MPR), while treatment persistence was determined by outpatient clinic appointment gaps.

RESULTSA total of 94 rivaroxaban and 137 warfarin users were analysed by complete case analysis. The MPR of warfarin patients was lower than rivaroxaban patients by 10% (95% CI, 6.4% to 13.6%; P <0.0001). Also, there were more warfarin patients who had gaps in treatment persistence compared to those prescribed rivaroxaban (8.0% vs 1.1%; P = 0.03). Significant factors affecting medication adherence were age and duration of anticoagulant use. For every 10-year increase in age, MPR increased by 1.7% (95% CI, 0.7% to 2.8%). Similarly, for every year increase in duration of use, MPR increased by 1.8% (95% CI, 0.6% to 3.0%). Race, gender, concomitant medication and type of residence were not found to be significant covariates in the multivariable analysis.

CONCLUSIONPatients on rivaroxaban are likely to be more adherent to their prescribed oral anticoagulant with increasing age and duration of treatment influencing adherence.

Adult ; Age Factors ; Anticoagulants ; therapeutic use ; Databases, Factual ; Factor Xa Inhibitors ; therapeutic use ; Female ; Humans ; Male ; Medication Adherence ; statistics & numerical data ; Middle Aged ; Pulmonary Embolism ; drug therapy ; Retrospective Studies ; Rivaroxaban ; therapeutic use ; Singapore ; Venous Thrombosis ; drug therapy ; Warfarin ; therapeutic use