【Introduction】 We report our experience treating venous thromboembolism (VTE) with DOACs at our hospital. 【Subjects and Methods】 We retrospectively reviewed patients treated with edoxaban or ...rivaroxaban for VTE from November 2014 to September 2016 at our hospital. We compared the efficacy and safety of these two DOACs. We evaluated efficacy by incidence of thromboembolic events and safety by incidence of bleeding episodes. 【Result】 92 patients with VTE received treatment with edoxaban or rivaroxaban during the study period. 71 patients (77.2%) were treated with edoxaban and 21 patients (22.8%) patients were treated with Rivaroxaban. There were more patients with temporary VTE risk factors in the edoxaban group and more cancer patients in the rivaroxaban group. Many asymptomatic DVT patients and distal DVT patients who were not covered in previous RCT were included in this study. Many patients received treatment at a reduced dose and relatively few patients received the regular dose. Thromboembolic events in the edoxaban and rivaroxaban groups occurred in 4 patients (5.6%) and no patients (0%), respectively. There was no statistically significant difference between the two groups (P=0.362). Bleeding episodes in the edoxaban and rivaroxaban groups occurred in 10 patients (14.1%) and 2 patients (9.5%), respectively. There was no statistically significant difference between the two groups (P=0.719). Major bleeding occurred in 2 patients (2.8%) in the edoxaban group and 1 patient (4.8%) in the rivaroxaban group. During the study period, 6 patients (8.5%) in the edoxaban group and 1 patient (4.8%) in the rivaroxaban group died. There were no VTE-related deaths in either group (P=0.271). Cause of death was cancer in all cases. 【Conclusion】 Although patient characteristics were different, the efficacy and safety of these two DOACs for treatment of VTE were similar in our study.
Comparing kidney disease progression among patients treated with direct oral anticoagulants (DOACs) versus warfarin has not been well studied. We hypothesized that apixaban would be associated with ...lower risks of progression of chronic kidney disease (CKD) and progression to incident kidney failure than warfarin in patients with atrial fibrillation (AF).
Retrospective cohort study.
Medicare recipients with stage 3, 4, or 5 CKD and incident AF who received a new prescription for apixaban or warfarin from 2013 through 2017.
Apixaban or warfarin.
Progression to incident kidney failure or, separately, to a more advanced stage of CKD.
Marginal structural cause-specific proportional hazards models with inverse probability weighting to estimate marginal hazard ratios (HRs) for each outcome. HRs compared apixaban to warfarin in intention-to-treat and censored-at-drug-switch analyses.
12,816 individuals met inclusion criteria (50.3% received apixaban; 49.7% received warfarin). After weighting, the mean age of the cohort was 80 ± 7 years, 51% were women, and 88% were White. Approximately 84% had stage 3, 15% had stage 4, and 1% had stage 5 CKD. In the intention-to-treat analysis, apixaban, relative to warfarin, was associated with an HR of developing incident kidney failure of 0.98 (95% confidence interval CI, 0.79-1.22) and of CKD stage progression of 0.90 (95% CI, 0.82-0.99). Corresponding HRs for censored-at-drug-switch analyses were 0.81 (95% CI, 0.56-1.17) and 0.81 (95% CI, 0.70-0.92). Results were similar for a series of subgroup and sensitivity analyses.
CKD was defined based on diagnosis codes from claims; findings may not be generalizable to non-Medicare CKD populations.
Apixaban, compared with warfarin, was associated with lower risk of CKD stage progression, but not with incident kidney failure.
Display omitted
Direct oral anticoagulants (DOACs) represent a cornerstone of adult venous thromboembolism (VTE) treatment. Recently, randomized controlled trials (RCTs) investigating DOACs in pediatrics have been ...performed.
To evaluate the efficacy and safety of DOACs in the pediatric population.
We systematically searched MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov from initiation up to August 20, 2022, for RCTs comparing DOACs to standard of care (SOC) in patients aged <18 years according to PRISMA guidelines (PROSPERO registration CRD42022353870). The primary analysis was performed according to the anticoagulation intensity and clinical setting (ie, prophylaxis in cardiac disease or treatment in VTE). Efficacy outcomes were all-cause mortality and VTE. Safety outcomes were major bleeding (MB), clinically relevant non-MB, any bleeding, serious adverse events, and discontinuation due to adverse events (AEs).
Seven RCTs were included in the systematic review and 6 in the meta-analysis (3 prophylaxis in cardiac disease and 3 treatment in VTE). DOACs showed a significant reduction of VTE recurrence for treatment (odds ratio OR = 0.42; 95% CI, 0.19–0.94) and a nonsignificant reduction in VTE occurrence in prophylaxis (OR = 0.22; 95% CI, 0.03–1.55). No differences were observed for any bleeding, serious AEs, and MB in prophylaxis. Nonsignificant trends were observed for clinically relevant non-MB, MB in treatment, and discontinuation due to AE in prophylaxis. We found a significant increase in discontinuation due to AE in treatment.
DOAC treatment seems to reduce VTE compared with SOC without major safety issues in the pediatric population, whereas DOAC prophylaxis seems at least comparable to SOC.
•Recent clinical trials investigated direct oral anticoagulants (DOACs) in pediatric patients.•In RCTs, DOAC treatment reduced venous thromboembolism recurrence.•DOAC prophylaxis was at least comparable to standard of care.•The safety profile was generally comparable between DOACs and the standard of care.
Background: The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of ...Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs (Direct oral anticoagulants) in patients with COVID-19 was the basis for conducting this study. Aim: The objective of this study was to assess DOAC consumption and expenditure in the Russian Federation during the COVID-19 pandemic and to analyze whether it was supported by the domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs (Clinical practice guidelines) for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. We searched Russian databases for CPGs, published between 2020 and 2023. We identified seven relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using an AGREE II questionnaire. We calculated DOAC DDD (defined daily dose) consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020–2022. Results: Seven clinical CPGs were analyzed with the AGREE II tool. It was revealed that experts gave the highest scores for the sections on scope and purpose (from 62.98% to 100%), and clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections on stakeholder involvement (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), and editorial independence (from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores—ROPNIZ (Livzan), and ROPNIZ (Drapkina). The minimum score was registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), or 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020—26.59 DDD per patient with COVID-19; in 2021—15.75 DDD per patient with COVID-19), and in 2022—10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 it decreased to 5.48 DDD, which is 2.74 times less than recommended. Conclusions: Analysis of seven clinical recommendations revealed that such sections of clinical recommendations as scope, purpose, and clarity of presentation had the highest degree of assessment in accordance with AGREE II. The lowest scores were given for the sections on stakeholder involvement, rigour of development, applicability, and editorial independence. When comparing the total score, it was found that two clinical guidelines received the highest scores—the Russian Society for the Prevention of Non-communicable Diseases (Livzan), and the Russian Society for the Prevention of Non-communicable Diseases (Drapkina). The minimum score was registered with the Research Institute for Healthcare Organization and Medical Management of Moscow Healthcare Department clinical guideline. No guideline received a total score of more than 70%. During the pandemic, the highest DDD consumption of DOACs was in 2020, which exceeded the DOACs’ recommended DDD by Russian clinical guidelines. DOAC consumption had decreased by 2022. There was a decrease in the consumption of rivaroxaban, with an increase in apixaban’s share in the structure of DOAC consumption during the coronavirus pandemic. Obtained data indicate that in 2021 the apixaban consumption in the Russian Federation corresponded to the recommended DDD in the national guidelines, which indicates the most correct use of apixaban according to Russian GPGs.
Direct oral anticoagulants (DOACs) represent a new generation of drugs that have been increasingly used in the prevention and treatment of thromboembolic states. According to the mechanism of ...anticoagulant action, DOACs are divided into two groups: direct inhibitors of thrombin (dabigatran) and direct inhibitors of activated factor X (FXa) (rivaroxaban, apixaban, edoxaban, betrixaban). Compared to the vitamin K antagonists, DOACs are superior in terms of onset of action, pharmacokinetic and pharmacodynamics properties and fixed daily dose without the need for routine coagulation monitoring. Despite these advantages, there are clinical conditions in which laboratory measurement of DOACs should be performed. Although DOACs have an impact on screening haemostasis assays (prothrombin time, PT; activated partial thromboplastin time, aPTT; and thrombin time, TT), these tests are not appropriate for quantifying drug levels. Therefore, specific quantitative methods (LC-MS/MS as a gold standard method for all DOACs, coagulometric and chromogenic assays for dabigatran, and chromogenic anti-Xa assays with drug-specific calibrators for inhibitors of FXa) should only be used for determination of DOACs concentration. The aim of this review is to present all aspects of laboratory assessment of DOACs, including pre-analytical, analytical and post-analytical factors in the overall testing process with a special accent on the available specific quantitative methods for measurement of DOACs in circulation.
Clotting test results are currently not useful for estimating direct oral anti-coagulant (DOAC) concentrations because baseline results vary. DOAC Stop is a DOAC extracting agent with no effect on ...clotting factors. We investigated if aPTT (activated partial thromboplastin time) and dRVVT (dilute Russells viper venom time) results might correlate better with DOAC concentrations if results after DOAC extraction were used to estimate a “before/after” value (Correction Ratio).
We used activated partial thromboplastin time (aPTT, PTT-LA) and dilute Russells viper venom time clotting test (dRVVT) results previously recorded on DOAC patient plasmas (25 dabigatran, 15 apixaban, 19 rivaroxaban) without known thrombotic risk factors before and after DOAC extraction. DOAC concentrations had been determined by standard chromogenic assays.
Correlations between aPTT and dabigatran, apixaban, and rivaroxaban concentrations were initially poor (0.64, 0.15 and 0.39 respectively). However, they improved significantly to 0.94, 0.89 and 0.80 when the ratios of initial aPTT to the aPTT obtained after DOAC extraction were plotted against DOAC concentration. Still better correlations (0.99, 0.97, 0.95) and much higher sensitivities to the DOACs were obtained when dRVVT (LA Confirm) tests were used following this procedure on the same samples.
The correlations of aPTT and dRVVT tests with DOAC concentrations were significantly improved by using the ratio of result “before” to those “after” DOAC extraction. The results indicate that dRVVT (especially LA Confirm) and similar tests might be useful for determining DOAC concentrations more reliably and with better sensitivity than currently possible with clotting tests.
•Extraction of DOACs by DOAC Stop allows baseline clotting test results to be estimated•The “Correction Ratio” is the clotting test result before divided by that after DOAC extraction.•The CR correlated much better with DOAC concentration than initial results.•The best test for this was high phospholipid dRVVT reagent.•This procedure permits quick estimation of DOACs from simple clotting tests via appropriate calibration curves.
This guidance document focuses on the diagnosis and treatment of venous thromboembolism (VTE). Efficient, cost effective diagnosis of VTE is facilitated by combining medical history and physical ...examination with pre-test probability models, D dimer testing and selective use of confirmatory imaging. Clinical prediction rules, biomarkers and imaging can be used to tailor therapy to disease severity. Anticoagulation options for acute VTE include unfractionated heparin, low molecular weight heparin, fondaparinux and the direct oral anticoagulants (DOACs). DOACs are as effective as conventional therapy with LMWH and vitamin K antagonists. Thrombolytic therapy is reserved for massive pulmonary embolism (PE) or extensive deep vein thrombosis (DVT). Inferior vena cava filters are reserved for patients with acute VTE and contraindications to anticoagulation. Retrievable filters are strongly preferred. The possibility of thoracic outlet syndrome and May-Thurner syndrome should be considered in patients with subclavian/axillary and left common iliac vein DVT, respectively in absence of identifiable triggers. The optimal duration of therapy is dictated by the presence of modifiable thrombotic risk factors. Long term anticoagulation should be considered in patients with unprovoked VTE as well as persistent prothrombotic risk factors such as cancer. Short-term therapy is sufficient for most patients with VTE associated with transient situational triggers such as major surgery. Biomarkers such as D dimer and risk assessment models such the Vienna risk prediction model offer the potential to customize VTE therapy for the individual patient. Insufficient data exist to support the integration of bleeding risk models into duration of therapy planning.
Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. ...The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern.
We evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study.
Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio HR = 1.14; 0.55–2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34–1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51–1.00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40–1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66–4.79), and death occurred in 87 (26.2%) and 66 (26.7%) patients, respectively (HR = 0.85; 0.62–1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4.
In our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.
•Anticancer agents did not influence rates of primary outcomes during anticoagulation.•No interaction between apixaban and CYP3A4 or permeability glycoprotein inducers or inhibitors was found.•Anticancer agents can be concomitantly administered to apixaban-treated patients with venous thromboembolism.•An increased risk of clinically relevant non-major bleeding was observed in apixaban-treated patients with colorectal and lung cancer.
Deep vein thrombosis (DVT) is a major preventable cause of morbidity and mortality worldwide. Venous thromboembolism (VTE), which includes DVT and pulmonary embolism (PE), affects an estimated 1 per ...1,000 people and contributes to 60,000–100,000 deaths annually. Normal blood physiology hinges on a delicate balance between pro- and anti-coagulant factors. Virchow’s Triad distills the multitude of risk factors for DVT into three basic elements favoring thrombus formation: venous stasis, vascular injury, and hypercoagulability. Clinical, biochemical, and radiological tests are used to increase the sensitivity and specificity for diagnosing DVT. Anticoagulation therapy is essential for the treatment of DVT. With few exceptions, the standard therapy for DVT has been vitamin K-antagonists (VKAs) such as warfarin with heparin or fractionated heparin bridging. More recently, a number of large-scale clinical trials have validated the use of direct oral anticoagulants (DOACs) in place of warfarin in select cases. In this review, we summarize the pathogenesis, diagnosis, and medical management of DVT, with particular emphasis on anticoagulation therapy and the role of DOACs in the current treatment algorithm.
PDF
