D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with non-vitamin K anticoagulants.
ABSTRACT: BACKGROUND:D-dimer levels measured during and after vitamin K antagonist withdrawal may be used in clinical practice to assess the individual risk of recurrent venous thromboembolism. Currently, direct oral anticoagulants (DOACs) are frequently used in venous thromboembolism treatment; however, their pharmacokinetics and pharmacodynamics characteristics are completely different than vitamin K antagonists. The present study aimed at comparing the results of D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with DOACs or warfarin. MATERIAL AND METHODS:D-dimer levels were measured in 527 patients ("cases") during DOACs treatment (T0) and after 15 (T15), 30 (T30), 60 (T60) and 90 (T90) days after their discontinuation and in 527 patients ("controls") enrolled in the DULCIS study (all treated with warfarin), matched for sex, age (+/-3 y), type of D-dimer assay and site of venous thromboembolism. Both cases and controls received anticoagulant treatment after a first venous thromboembolism event that was unprovoked or associated with weak risk factors. RESULTS:The rate of positive D-dimer results was significantly higher in cases than in controls at T0 (10.8% vs 5.1%, p = 0.002) and at T30 (18.8% vs 11.8%, p = 0.019), as well as at the other time-points, though not statistically significant. CONCLUSION:D-dimer levels during and after stopping an anticoagulant treatment for a venous thromboembolism episode differ between patients treated with a DOAC than in those treated with warfarin. Specifically designed prospective studies are warranted to reassess the use of D-dimer as predictor of the risk of recurrent venous thromboembolism in patients treated with DOACs.
Project description:Randomized clinical trials comparing direct oral anticoagulants (DOACs) to warfarin in cancer patients have not been performed. We evaluated the effectiveness and associated risk of DOACs vs warfarin, as well as comparisons of DOACs, in a large population of cancer patients with nonvalvular atrial fibrillation (AF). Using the MarketScan databases, we identified 16?096 AF patients (mean age, 74 years) initiating oral anticoagulant and being actively treated for cancer between 2010 and 2014. Anticoagulant users were matched by age, sex, enrollment date, and drug initiation date. Study end points were identified with diagnostic codes and included ischemic stroke, severe bleeding, other bleeding, and venous thromboembolism (VTE). Cox regression was used to estimate associations of anticoagulants with study end points. Compared with warfarin, rates of bleeding (hazard ratio [95% confidence interval]) were similar in rivaroxaban (1.09 [0.79, 1.39]) and dabigatran (0.96 [0.72, 1.27]) users, whereas apixaban users experienced lower rates (0.37 [0.17, 0.79]). Rates of ischemic stroke did not differ among anticoagulant users. Compared with warfarin, rate of VTE (hazard ratio [95% confidence interval]) was lower among rivaroxaban (0.51 [0.41, 0.63]), dabigatran (0.28 [0.21, 0.38]), and apixaban (0.14 [0.07, 0.32]) users. In head-to-head comparisons among DOACs, dabigatran users had lower rates of VTE than rivaroxaban users; apixaban users had lower rates of VTE and severe bleeding than rivaroxaban users. In this population of patients with AF and cancer, DOAC users experienced lower or similar rates of bleeding and stroke compared with warfarin users, and a lower rate of incident VTE.
Project description:Essentials Bleeding risk by anticoagulant choice for cancer-associated venous thrombosis (CA-VTE) is unknown. 26 894 people with CA-VTE were followed for bleeding in a claims database in the United States. Hospitalized bleeding risk was similar with direct acting oral anticoagulants vs. warfarin. Relative hospitalized bleeding risk varied by cancer type and anticoagulant choice. SUMMARY: Background Direct acting oral anticoagulants (DOACs) are associated with less bleeding than traditional venous thromboembolism (VTE) treatments in the general population but are little studied in cancer-associated VTE (CA-VTE). Objective To determine whether different anticoagulation strategies for CA-VTE have different hospitalized bleeding rates. Patients/Methods We conducted a retrospective study of patients with CA-VTE, diagnosed between 2011 and 2015, in a large administrative database. Using validated algorithms, we identified 26 894 CA-VTE patients treated with anticoagulants and followed them for hospitalized severe bleeding. Cox models were used to assess bleeding risk, adjusted for age, sex, high dimensional propensity score and frailty. Results Over 27 281 person-years of follow-up (median 0.6 years), 1204 bleeding events occurred, for a bleeding rate of 4.4% per patient-year. Bleeding rates varied by cancer type, with the highest rate for upper gastrointestinal cancers (8.6%) and the lowest for breast cancer (2.9%). In Cox models (hazard ratio [HR]; 95% confidence interval [CI]), compared with warfarin, DOACS and low-molecular-weight heparin (LMWH) had similar hazards of bleeding (HR, 0.88; 95% CI, 0.69-1.11 and 0.98; 0.85-1.13). Compared with LMWH, there was no difference in hazard of bleeding with DOACs (0.86; 0.66-1.12). There was heterogeneity in bleeding risk with DOACs by cancer type, with a higher risk of bleeding in upper gastrointestinal cancers and lower risk of bleeding in prostate cancer and hematologic cancers. Conclusions In this practice-based sample of CA-VTE patients, DOACs were associated with similar bleeding risks to warfarin and LMWH. These findings suggest a complex association of bleeding risk with anticoagulant choice in cancer patients.
Project description:Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism.Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016.Setting Community based, using healthcare data from six jurisdictions in Canada and the United States.Participants 59?525 adults (12?489 DOAC users; 47?036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis.Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites.Results Of the 59?525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients.Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment.Trial registration Clinical trials NCT02833987.
Project description:Oral anticoagulants used for the primary treatment of venous thromboembolism (VTE) include warfarin and the more recently introduced direct oral anticoagulants (DOACs), including rivaroxaban, apixaban, dabigatran and edoxaban. Information on the comparative safety of these medications in routine clinical practice is lacking. We identified patients with diagnoses for VTE and prescriptions for oral anticoagulants using claims data from a large U.S. insurance database from 2012 to 2017. Marginal structural logistic models were used to examine associations between type of oral anticoagulant and risk of all-cause mortality. Of 62,431 enrolees in this analysis, 51% were female and the mean age was 61.9 years. Initial oral anticoagulant prescriptions were for warfarin (n?=?35,704), rivaroxaban (n?=?21,064) and apixaban (n?=?5,663). A total of 1,791 deaths occurred within 6 months of the initial oral anticoagulant prescription. Risk of all-cause mortality was not associated with having a prescription for warfarin versus any DOAC or between any head-to-head DOAC comparisons. Also, associations generally did not vary when stratified by VTE type, sex, age, co-morbidities (including renal disease) or anti-platelet medication use. In this observational study, the associations with all-cause mortality comparing DOACs versus warfarin agree with results from previous clinical trials and observational studies, while the associations for head-to-head DOAC comparisons provide new information on the comparative safety of DOACs. Our findings suggest that other criteria such as patient preference, cost, recurrent VTE risk or bleeding risk should be used when determining the choice of anticoagulant for the primary treatment of VTE.
Project description:BACKGROUND:Warfarin is an anticoagulant medication proven effective in the initial treatment and secondary prevention of venous thromboembolism. Anti-Xa direct oral anticoagulants are alternatives to warfarin; however there is limited data assessing satisfaction after switching from warfarin to an anti-Xa direct oral anticoagulant in patients for treatment of venous thromboembolism. OBJECTIVES:To assess medication satisfaction in patients requiring anticoagulation for venous thromboembolism after conversion from warfarin to an anti-Xa direct oral anticoagulant. METHODS:A retrospective cohort study with prospective assessment of satisfaction and review of adverse events following anti-Xa direct oral anticoagulant replacement of warfarin for treatment of venous thromboembolism. Out of 165 patients who had switched from warfarin to rivaroxaban or apixaban from an outpatient haematology practice, 126 patients consented for a survey of patient's relative satisfaction of anti-Xa direct oral anticoagulant therapy compared with previous warfarin therapy using the Anti-Clot Burden and Benefits Treatment Scale and SWAN Score. RESULTS:The mean Anti-Clot Burden and Benefits and SWAN Score was 93% (56/60) and 83% (24.8/30) respectively reflecting high satisfaction with anti-Xa direct oral anticoagulants. 120 patients stated preference for anti-Xa direct oral anticoagulants over warfarin. Leading perceptions driving this was the reduction in frequency of medical contact and fewer bleeding side effects. Thirteen patients (10.3%) experienced an adverse event after the anti-Xa direct oral anticoagulant switch (majority were non-major bleeding) but most remained on anti-Xa direct oral anticoagulant treatment after management options were implemented with continued high satisfaction scores. CONCLUSIONS:Patient satisfaction with anti-Xa direct oral anticoagulant therapy for the treatment and prevention of venous thromboembolism after switching from warfarin in routine clinical practice appeared high. Improved patient convenience including reduced frequency of medical contact and fewer unpredictable side effects were perceived as significant advantages of anti-Xa direct oral anticoagulants compared to warfarin.
Project description:Existing research comparing hospital length of stay for patients treated with non-vitamin K oral anticoagulants or parenteral bridging to warfarin has been conducted primarily with the agent rivaroxaban. The objective of this study was to compare hospital length of stay between patients initiated on the non-vitamin K oral anticoagulants, apixaban or rivaroxaban, and patients initiated on parenteral anticoagulation agents plus warfarin for the treatment of venous thromboembolism.A retrospective cohort study was conducted at an 859-bed, not-for-profit, teaching hospital. Adult patients admitted for a primary diagnosis of venous thromboembolism between 1 November 2012 and 31 August 2015 and treated with apixaban or rivaroxaban or a parenteral anticoagulant plus warfarin were included in the study. Eligible patients were identified using International Classification of Diseases, Ninth Revision codes for a primary diagnosis of acute thromboses and emboli and medication administration record data. Individuals using anticoagulation therapy prior to admission, released from the emergency department, or treated with thrombectomy or fibrinolytic therapy were excluded.A total of 152 patients were included in this study. Patient characteristics, including renal function, were similar between study arms. Venous thromboembolism treatment with apixaban or rivaroxaban compared to a parenteral anticoagulant plus warfarin was associated with a reduced hospital length of stay (2.63 vs 5.33 days; p < 0.05) and decreased total hospital cost adjusted to 2015 dollars (US$21,694 vs US$38,851; p = 0.013).These results suggest that treatment with a non-vitamin K anticoagulant may significantly reduce hospital length of stay and total hospital cost compared to a parenteral anticoagulant plus warfarin for patients admitted for venous thromboembolism.
Project description:Background:Direct oral anticoagulants (DOACs), namely rivaroxaban, apixaban, dabigatran, and edoxaban, are now included together with warfarin as standards of care for the primary treatment of venous thromboembolism (VTE). The extent to which the DOACs have been adopted since receiving US Food and Drug Administration (FDA) approval is unknown. Objective:To document temporal trends in oral anticoagulant (OAC) prescriptions among anticoagulant-naïve patients initiating OACs for VTE primary treatment in the United States and to report participant characteristics by OAC prescribed for the year 2017. Methods:MarketScan databases for years 2012 through 2017 were used to identify VTE cases and comorbidities using International Classification of Diseases codes and prescriptions for OACs via outpatient pharmaceutical claims data. Results:The 137 203 VTE cases were on average (± standard deviation) 56.7 ± 16.0 years old and 49.9% female. Warfarin was prescribed to 98.7% of VTE patients receiving an OAC in quarter 1 (January through March) of 2012. By quarter 4 (October through December) of 2017, warfarin was prescribed to 17.5%, while rivaroxaban was prescribed to 42.7%, apixaban to 38.6%, dabigatran to 1.3%, and edoxaban to <0.1%. In 2017, the comorbidity burden was highest among patients prescribed warfarin, intermediate among patients prescribed apixaban, and lowest among patients prescribed rivaroxaban. Conclusions:Rivaroxaban and apixaban use to treat VTE has increased dramatically since receiving FDA approval, whereas warfarin use has plummeted. Dabigatran and edoxaban are infrequently prescribed. Given widespread usage of rivaroxaban and apixaban, there is a need for continued monitoring of the comparative effectiveness of these OAC therapies in real-world settings.
Project description:Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected. As APS is a heterogeneous condition, its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors. Although literature data are conflicting regarding primary prophylaxis, there is some evidence indicating that antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile. In patients with thrombotic APS, current evidence-based guidelines recommend lifelong vitamin K antagonists (VKAs), preferably warfarin. The optimal intensity of anticoagulation following arterial thrombosis remains controversial. Arterial thrombosis should be treated either with high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0-3.0). It is recommended to avoid direct oral anticoagulants (DOACs) in patients with high-risk APS, mainly those with triple-positive PL and previous arterial events. They would only be used exceptionally in selected patients with low-risk venous thromboembolism (VTE). In low-risk VTE patients currently treated with a DOAC due to warfarin intolerance or a previous unstable International Normalized Ratio on warfarin, the decision of continuing DOACs would be taken in carefully selected patients. In women with obstetric APS, the combination therapy with LDA plus heparin remains the conventional strategy.
Project description:Venous thromboembolism (VTE) is a serious medical condition associated with significant morbidity and mortality, and an incidence that is expected to double in the next forty years. The advent of direct oral anticoagulants (DOACs) has catalyzed significant changes in the therapeutic landscape of VTE treatment. As such, it is imperative that clinicians become familiar with and appropriately implement new treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for VTE treatment with the DOACs. When possible, guidance statements are supported by existing published evidence and guidelines. In instances where evidence or guidelines are lacking, guidance statements represent the consensus opinion of all authors of this manuscript and are endorsed by the Board of Directors of the Anticoagulation Forum.The authors of this manuscript first developed a list of pivotal practical questions related to real-world clinical scenarios involving the use of DOACs for VTE treatment. We then performed a PubMed search for topics and key words including, but not limited to, apixaban, antidote, bridging, cancer, care transitions, dabigatran, direct oral anticoagulant, deep vein thrombosis, edoxaban, interactions, measurement, perioperative, pregnancy, pulmonary embolism, reversal, rivaroxaban, switching, \thrombophilia, venous thromboembolism, and warfarin to answer these questions. Non- English publications and publications > 10 years old were excluded. In an effort to provide practical information about the use of DOACs for VTE treatment, answers to each question are provided in the form of guidance statements, with the intent of high utility and applicability for frontline clinicians across a multitude of care settings.
Project description:Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy for more than 50 years. VKAs are mainly used for the prevention of stroke in patients with atrial fibrillation (AF) and the treatment and secondary prevention of venous thromboembolism. In the past 5 years, four new agents-the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban and the direct thrombin inhibitor dabigatran [collectively known as direct oral anticoagulants (DOACs) or non-VKA oral anticoagulants]-have been approved for these and other indications. Despite these new treatment options, the VKA warfarin currently remains the most frequently prescribed oral anticoagulant. The availability of DOACs provides an alternative management option for patients with AF, especially when the treating physician is hesitant to prescribe a VKA owing to associated limitations, such as food and drug interactions, and concerns about bleeding complications. Currently available real-world evidence shows that DOACs have similar or improved effectiveness and safety outcomes compared with warfarin. Treatment decisions on which DOAC is best suited for which patient to maximize safety and effectiveness should take into account not only clinically relevant patient characteristics but also patient preference. This article reviews and highlights real and perceived implications of VKAs for the prevention of stroke in patients with non-valvular AF, with specific reference to their strengths and weaknesses compared with DOACs.