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Archives of Pathology & Laboratory... Jan 2022Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios.
CONTEXT.—
Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios.
OBJECTIVE.—
To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants.
DESIGN.—
College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed.
RESULTS.—
For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, and 6.8% to 9.0% for 100-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The CV for diluted thrombin time for dabigatran was better overall (ranging from 11.6% to 17.2%, 9.3% to 12.3, and 7.1% to 11.2% for 100 ng/mL, 200 ng/mL, and 400 ng/mL, respectively). The rivaroxaban-calibrated anti-Xa assay CVs also showed variability (ranging from 11.5% to 22.2%, 7.2% to 10.9%, and 6.4% to 8.1% for 50-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed variable dose- and reagent-dependent responsiveness to DOACs: PT was more responsive to rivaroxaban and aPTT to dabigatran. The undiluted thrombin time showed maximum prolongation across all 3 dabigatran concentrations, making it too sensitive for drug-level monitoring, but supporting its use as a qualitative screening assay.
CONCLUSIONS.—
DOAC-specific assays performed reasonably well. While PT and aPTT cannot be used safely to determine DOAC degree of anticoagulation, a normal thrombin time excludes the presence of dabigatran.
Topics: Administration, Oral; Anticoagulants; Antithrombins; Blood Coagulation Tests; Dabigatran; Humans; Partial Thromboplastin Time; Pyrazoles; Pyridones; Rivaroxaban
PubMed: 34133726
DOI: 10.5858/arpa.2020-0633-CP -
JAMA Network Open Nov 2023There are no data on patient-centered outcomes and health care costs by frailty in patients with atrial fibrillation (AF) taking oral anticoagulants (OACs).
IMPORTANCE
There are no data on patient-centered outcomes and health care costs by frailty in patients with atrial fibrillation (AF) taking oral anticoagulants (OACs).
OBJECTIVE
To compare home time, clinical events, and health care costs associated with OACs by frailty levels in older adults with AF.
DESIGN, SETTING, AND PARTICIPANTS
This community-based cohort study assessed Medicare fee-for-service beneficiaries 65 years or older with AF from January 1, 2013, to December 31, 2019. Data analysis was performed from January to December 2022.
EXPOSURES
Apixaban, rivaroxaban, and warfarin use were measured from prescription claims. Frailty was measured using a validated claims-based frailty index.
MAIN OUTCOMES AND MEASURES
Outcome measures were (1) home time (days alive out of the hospital and skilled nursing facility) loss greater than 14 days; (2) a composite end point of ischemic stroke, systemic embolism, major bleeding, or death; and (3) total cost per member per year after propensity score overlap weighting.
RESULTS
The weighted population comprised 136 551 beneficiaries, including 45 950 taking apixaban (mean [SD] age, 77.6 [7.3] years; 51.3% female), 45 320 taking rivaroxaban (mean [SD] age, 77.6 [7.3] years; 51.9% female), and 45 281 taking warfarin (mean [SD] age, 77.6 [7.3] years; 52.0% female). Compared with apixaban, rivaroxaban was associated with increased risk of home time lost greater than 14 days (risk difference per 100 persons, 1.8 [95% CI, 1.5-2.1]), composite end point (rate difference per 1000 person-years, 21.3 [95% CI, 16.4-26.2]), and total cost (mean difference, $890 [95% CI, $652-$1127]), with greater differences among the beneficiaries with frailty. Use of warfarin relative to apixaban was associated with increased home time lost (risk difference per 100 persons, 3.2 [95% CI, 2.9-3.5]) and composite end point (rate difference per 1000 person-years, 29.4 [95% CI, 24.5-34.3]), with greater differences among the beneficiaries with frailty. Compared with apixaban, warfarin was associated with lower total cost (mean difference, -$1166 [95% CI, -$1396 to -$937]) but higher cost when excluding OAC cost (mean difference, $1409 [95% CI, $1177 to $1642]) regardless of frailty levels.
CONCLUSIONS AND RELEVANCE
In older adults with AF, apixaban was associated with increased home time and lower rates of clinical events than rivaroxaban and warfarin, especially for those with frailty. Apixaban was associated with lower total cost compared with rivaroxaban but higher cost compared with warfarin due to higher OAC cost. These findings suggest that apixaban may be preferred for older adults with AF, particularly those with frailty.
Topics: United States; Humans; Aged; Female; Male; Atrial Fibrillation; Warfarin; Rivaroxaban; Cohort Studies; Frailty; Medicare; Anticoagulants; Health Care Costs
PubMed: 37943558
DOI: 10.1001/jamanetworkopen.2023.42264 -
BMC Neurology Feb 2021New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events...
BACKGROUND
New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events due to their lower bleeding risk. There is a lack of evidence on the effectiveness and safety of Rivaroxaban in Cerebral venous thrombosis (CVT). This study aims to assess the effectiveness and bleeding risk of Rivaroxaban in comparison with Warfarin for the treatment of CVT.
MATERIALS AND METHODS
36 patients with diagnosis of CVT were included. Clinical and background information was assessed on admission and patients were followed for at least 12 months. Measured outcomes were modified Rankin Scale (mRS), evidence of recanalization on contrast-enhanced Brain MR venography (MRV) and major or minor bleeding. Patients were divided into two groups according to the type of oral anticoagulant (Rivaroxaban vs Warfarin). Groups were compared in terms of final outcomes and side effects.
RESULT
Overall, 13 (36.11%) patients received Warfarin and 23 (63.89%) received Rivaroxaban. Optimal mRS score (0-1) was attained in 9 of 10 (90%) of patients treated with Rivaroxaban and 19 of 22 (86.36%) of patients received Warfarin. MRV showed complete or partial recanalization in 12 of 14 (85.71%) patients treated with Rivaroxaban and all patients in the Warfarin group. There was no significant difference between the two groups in terms of major and minor hemorrhage.
CONCLUSION
Rivaroxaban holds promise for the treatment of CVT.
Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin
PubMed: 33588777
DOI: 10.1186/s12883-021-02091-1 -
Clinical and Applied... 2024To examine the effectiveness of rivaroxaban compared to enoxaparin in patients diagnosed with cancer and venous thromboembolism. (Meta-Analysis)
Meta-Analysis Comparative Study Review
OBJECTIVE
To examine the effectiveness of rivaroxaban compared to enoxaparin in patients diagnosed with cancer and venous thromboembolism.
METHODS
A search of Pub Med, Scopus, and Google Scholar, from inception through April 2023 was conducted. Articles comparing rivaroxaban with enoxaparin in patients with cancer and VTE/PE/DVT were included. Review Manager Version 5.2 was utilised for the analysis of the following outcomes; VTE, PE, DVT, major bleeding, and mortality.
RESULTS
A total of 8 articles and 2276 patients were included in the final analysis. Pooled analysis showed that rivaroxaban had a statistically insignificant reduced association with VTE occurrence (RR:0.83, 95% CI:0.58-1.18, P:0.3) as well as a statically insignificant reduction in major bleeding (RR:0.79, 95% CI:0.53-1.18, P:0.25). Analysis showcased that there was an insignificant reduction of mortality rivaroxaban as compared to enoxaparin (RR:0.74, 95% CI: 0.46-1.20, P:0.23).
CONCLUSION
Rivaroxaban can serve as a viable alternative to enoxaparin, with no appreciable drawbacks, for preventing and managing VTE in patients with malignancy.
Topics: Humans; Anticoagulants; Enoxaparin; Hemorrhage; Neoplasms; Recurrence; Rivaroxaban; Venous Thromboembolism
PubMed: 38870350
DOI: 10.1177/10760296241261364 -
Therapeutic Advances in Cardiovascular... Oct 2016Being overweight or obese is associated with a higher individual risk of venous thromboembolism and poorer postprocedural outcomes after hip or knee replacement surgery.... (Review)
Review
Being overweight or obese is associated with a higher individual risk of venous thromboembolism and poorer postprocedural outcomes after hip or knee replacement surgery. In addition, there is evidence that obesity represents a significant driving factor for the current and projected prevalence of atrial fibrillation. Rivaroxaban and other direct oral anticoagulants offer fixed-dose regimens for these indications. They do not require therapeutic drug monitoring or dose adjustment according to the weight of the patient. However, primary care physicians seem to be hesitant to accept the concept of a fixed-dose regimen for patients at extremes of weight, perhaps because of familiarity with weight-based dosing of other drugs including low molecular weight heparins. The main concerns related to unadjusted dosing are increased exposure in underweight patients leading to a risk of excessive bleeding and conversely to underanticoagulation of overweight patients. Rivaroxaban has shown similar efficacy and a similar or better safety profile compared with standard treatment for several venous and arterial indications, including venous thromboembolism, nonvalvular atrial fibrillation, and acute coronary syndrome. Prespecified subgroup analyses of patients stratified by weight or body mass index demonstrated outcomes that were consistent with the overall analysis and within each weight and body mass index group. The results suggest that standard-dose rivaroxaban can be safely prescribed in adult patients of all weights.
Topics: Body Mass Index; Body Weight; Clinical Trials, Phase III as Topic; Factor Xa Inhibitors; Humans; Rivaroxaban
PubMed: 27090286
DOI: 10.1177/1753944716643645 -
Critical Care (London, England) Aug 2016Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on... (Review)
Review
BACKGROUND
Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on encouraging results for efficacy and safety in clinical studies. An initial limitation of these new drugs was the absence of an adequate strategy to reverse the effect if a bleeding event occurs or an urgent invasive procedure has to be carried out.
MAIN TEXT
Specific reversing agents for DOACs have become available, however, and are now evaluated in clinical studies. For the anti-factor Xa agents (rivaroxaban, apixaban, and edoxaban) a number of studies have shown that the administration of prothrombin complex concentrate resulted in a correction of the prolonged prothrombin time and restored depressed thrombin generation after rivaroxaban treatment in a controlled trial in healthy human subjects. In view of the relatively wide availability of prothrombin complex concentrates, this would be an interesting option if the results can be confirmed in patients on oral factor Xa inhibitors who present with bleeding complications. More specific reversal can be achieved with andexanet, a new agent currently in development that competitively binds to the anti-factor Xa agents. For the direct thrombin inhibitor dabigatran, the administration of prothrombin complex concentrates showed variable results in various volunteer trials and efficacy at relatively high doses in animal studies. Recently, a Fab fragment of a monoclonal antibody (idarucizumab) was shown to be an effective reversal agent for dabigatran in human studies.
CONCLUSION
For the new generation of DOACs, several reversal strategies and specific antidotes are under evaluation, although most interventions need further evaluation in clinical trials.
Topics: Administration, Oral; Anticoagulants; Disease Management; Factor Xa Inhibitors; Hemorrhage; Humans; Incidence; Prothrombin Time; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Thiazoles
PubMed: 27543264
DOI: 10.1186/s13054-016-1413-3 -
Human Genomics Jul 2023The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly...
BACKGROUND
The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients.
PATIENTS AND METHODS
This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications.
RESULTS
A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (C/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the C/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci.
CONCLUSION
This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the C/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.
Topics: Humans; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; Atrial Fibrillation; Cytochrome P-450 CYP3A; Neoplasm Proteins; Polymorphism, Genetic; Prospective Studies; Rivaroxaban
PubMed: 37420302
DOI: 10.1186/s40246-023-00506-3 -
Journal of Thrombosis and Thrombolysis Apr 2023Rivaroxaban is a direct, oral factor Xa inhibitor that is used for the prevention and treatment of various thromboembolic disorders. Several preclinical and clinical... (Review)
Review
Rivaroxaban is a direct, oral factor Xa inhibitor that is used for the prevention and treatment of various thromboembolic disorders. Several preclinical and clinical studies have utilized specific molecules as biomarkers to investigate the potential role of rivaroxaban beyond its anticoagulant activity and across a range of biological processes. The aim of this review is to summarize the existing evidence regarding the use of blood-based biomarkers to characterize the effects of rivaroxaban on coagulation and other pathways, including platelet activation, inflammation and endothelial effects. After a literature search using PubMed, almost 100 preclinical and clinical studies were identified that investigated the effects of rivaroxaban using molecular biomarkers. In agreement with the preclinical data, clinical studies reported a trend for reduction in the blood concentrations of D-dimers, thrombin-antithrombin complex and prothrombin fragment 1 + 2 following treatment with rivaroxaban in both healthy individuals and those with various chronic conditions. Preclinical and also some clinical studies have also reported a potential impact of rivaroxaban on the concentrations of platelet activation biomarkers (von Willebrand factor, P-selectin and thrombomodulin), endothelial activation biomarkers (matrix metalloproteinase-9, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and inflammation biomarkers (interleukin-6, tumor necrosis factor-α and monocyte chemoattractant protein-1). Based on the results of biomarker studies, molecular biomarkers can be used in addition to traditional coagulation assays to increase the understanding of the anticoagulation effects of rivaroxaban. Moreover, there is preliminary evidence to suggest that rivaroxaban may have an impact on the biological pathways of platelet activation, endothelial activation and inflammation; however, owing to paucity of clinical data to investigate the trends reported in preclinical studies, further investigation is required to clarify these observations.
Topics: Humans; Rivaroxaban; Blood Coagulation; Factor Xa Inhibitors; Inflammation; Biomarkers; Anticoagulants
PubMed: 36746885
DOI: 10.1007/s11239-023-02776-z -
Journal of the American College of... Jul 2021
Topics: Humans; Peripheral Arterial Disease; Rivaroxaban
PubMed: 34294269
DOI: 10.1016/j.jacc.2021.05.023 -
Polish Archives of Internal Medicine Aug 2023Isolated distal deep vein thrombosis (IDDVT) is a frequent manifestation of venous thromboembolism (VTE), accounting for up to 50% cases of lower‑extremity deep vein... (Review)
Review
Isolated distal deep vein thrombosis (IDDVT) is a frequent manifestation of venous thromboembolism (VTE), accounting for up to 50% cases of lower‑extremity deep vein thrombosis (DVT). As compared with proximal DVT, IDDVT is more frequently associated with transient risk factors and less often occurs unprovoked or in the presence of permanent risk factors. IDDVT generally carries a significantly lower risk of proximal extension, post‑thrombotic syndrome, and recurrence than proximal DVT. Nevertheless, some patient subgroups, such as those with active cancer, other predisposing permanent risk factors, prior VTE, unprovoked IDDVT, persistently restricted mobility, and trifurcation or bilateral involvement, exhibit a non‑negligible recurrence risk. Unlike in proximal DVT, the optimal therapeutic management of IDDVT remains uncertain. In clinical practice, the vast majority of IDDVT patients are managed with anticoagulation rather than with surveillance serial compression ultrasonography, which tends to be reserved to individuals at a high bleeding risk. Available data seem to favor anticoagulant therapy over no anticoagulation, thanks to a significant reduction in the risk for proximal extension and recurrence, without increased bleeding risk. Recent results of the RIDTS (Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis) randomized clinical trial with rivaroxaban further support the use of anticoagulant therapy for 3 months over shorter durations (eg, ≤6 weeks). In this review, we offer an updated overview of the epidemiology, risk factors, and clinical course of IDDVT, with a focus on the therapeutic management in light of current guideline recommendations and most recent evidence. We also present real‑life clinical cases of IDDVT with proposed therapeutic approaches, and highlight major challenges and gaps in this field.
Topics: Humans; Venous Thromboembolism; Rivaroxaban; Recurrence; Venous Thrombosis; Anticoagulants; Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37548526
DOI: 10.20452/pamw.16543