Temporal trends in initiation of VKA, rivaroxaban, apixaban and dabigatran for the treatment of venous thromboembolism - A Danish nationwide cohort study.
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SUBMITTER: Sindet-Pedersen C
PROVIDER: S-EPMC5469820 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
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Temporal trends in initiation of VKA, rivaroxaban, apixaban and dabigatran for the treatment of venous thromboembolism - A Danish nationwide cohort study.
Sindet-Pedersen Caroline C Pallisgaard Jannik Langtved JL Staerk Laila L Berger Jeffrey S JS Lamberts Morten M Torp-Pedersen Christian C Gislason Gunnar H GH Olesen Jonas Bjerring JB
Scientific reports 20170613 1
Danish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apix ...[more]
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Project description:BackgroundHistorically, warfarin or aspirin have been the recommended therapeutic options for the extended treatment (>3 months) of VTE. Data from Phase III randomised controlled trials (RCTs) are now available for non-VKA oral anticoagulants (NOACs) in this indication. The current systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of anticoagulants for the extended treatment of VTE.MethodsElectronic databases (accessed July 2014 and updated April 2016) were systematically searched to identify RCTs evaluating apixaban, aspirin, dabigatran, edoxaban, rivaroxaban, and warfarin for the extended treatment of VTE. Eligible studies included adults with an objectively confirmed deep vein thrombosis, pulmonary embolism or both. A fixed-effect Bayesian NMA was conducted, and results were presented as relative risks (RRs). Sensitivity analyses examining (i) the dataset employed according to the time frame for outcome assessment (ii) the model used for the NMA were conducted.ResultsEleven Phase III RCTs (examining apixaban, aspirin, dabigatran, rivaroxaban, warfarin and placebo) were included. The risk of the composite efficacy outcome (VTE and VTE-related death) was statistically significantly lower with the NOACs and warfarin INR 2.0-3.0 compared with aspirin, with no significant differences between the NOACs. Treatment with apixaban (RR 0.23, 95% CrI 0.10, 0.55) or dabigatran (RR 0.55, 95% Crl 0.43, 0.71) was associated with a statistically significantly reduced risk of 'major or clinically relevant non-major bleed' compared with warfarin INR 2.0-3.0. Apixaban also showed a significantly reduced risk compared with dabigatran (RR 0.42, 95% Crl 0.18, 0.97) and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59). Sensitivity analyses indicate that results were dependent on the dataset, but not on the type of NMA model employed.ConclusionsResults from the NMA indicate that NOACs are an effective treatment for prevention of VTE or VTE-related death) in the extended treatment setting. However, bleeding risk differs between potential treatments, with apixaban reporting the most favourable profile compared with other NOACs, warfarin INR 2.0-3.0, and aspirin.
| S-EPMC4972314 | biostudies-literature
Project description:BackgroundIdentification of risk factors for venous thromboembolism (VTE) is of utmost importance to improve current prophylactic regimes and treatment guidelines. The extent to which a family history contributes to the risk of VTE needs further exploration.ObjectivesTo examine the relative rate of VTE in first-degree relatives compared with the general population.MethodsBy crosslinking Danish nationwide registries we identified patients with VTE between 1978 and 2012, and their familial relations. The first member in a family to acquire VTE was defined as the proband. All first-degree relatives to probands were followed from the VTE date of the proband and until an event (VTE), death, emigration, 100 year birthday or end of study: 31st of December 2012, whichever came first. The relative rate of VTE was estimated by standardized incidence ratios (SIR) using time-dependent Poisson regression models, with the general population as a fixed reference.ResultsWe identified 70,767 children of maternal probands, 66,065 children of paternal probands, and 29,183 siblings to sibling probands. Having a maternal proband or a paternal proband were associated with a significantly increased VTE rate of 2.15 (CI: 2.00-2.30) and 2.06 (CI: 1.92-2.21), respectively. The highest estimate of VTE was observed among siblings (adjusted SIR of 2.60 [CI: 2.38-2.83]). Noteworthy, the rate of VTE increased for all first-degree relatives when the proband was diagnosed with VTE in a young age (≤ 50 years).ConclusionA family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population.
| S-EPMC5199093 | biostudies-literature
Project description:AIMS:The aim of this study was to compare the risk of stroke or systemic embolism (SE) and major bleeding in patients with atrial fibrillation (AF) using dabigatran, rivaroxaban, and apixaban in routine clinical practice. METHODS AND RESULTS:Using nationwide registries in Norway from January 2013 to December 2017, we established a cohort of 52 476 new users of non-vitamin K antagonist oral anticoagulants (NOACs) with AF. Users of individual NOACs were matched 1:1 on the propensity score to create three pairwise-matched cohorts: dabigatran vs. rivaroxaban (20 504 patients), dabigatran vs. apixaban (20 826 patients), and rivaroxaban vs. apixaban (27 398 patients). Hazard ratios (HRs) for the risk of stroke or SE and major bleeding were estimated. In the propensity-matched comparisons of the risk of stroke or SE, the HRs were 0.88 [95% confidence interval (CI) 0.76-1.02] for dabigatran vs. rivaroxaban, 0.88 (95% CI 0.75-1.02) for dabigatran vs. apixaban, and 1.00 (95% CI 0.89-1.14) for apixaban vs. rivaroxaban. For the risk of major bleeding, the HRs were 0.75 (95% CI 0.64-0.88) for dabigatran vs. rivaroxaban, 1.03 (95% CI 0.85-1.24) for dabigatran vs. apixaban, and 0.79 (95% CI 0.68-0.91) for apixaban vs. rivaroxaban. CONCLUSION:In this nationwide study of patients with AF in Norway, we found no statistically significant differences in risk of stroke or SE in propensity-matched comparisons between dabigatran, rivaroxaban, and apixaban. However, dabigatran and apixaban were both associated with significantly lower risk of major bleeding compared with rivaroxaban.
| S-EPMC7073510 | biostudies-literature
Project description:ObjectiveTo compare effectiveness and safety of warfarin and the direct oral anticoagulants (DOAC) dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation in routine care.MethodsFrom nationwide registries, we identified treatment-naïve patients initiating warfarin, dabigatran, rivaroxaban or apixaban for non-valvular atrial fibrillation from July 2013 to December 2015 in Norway. We assessed prescription duration using reverse waiting time distribution. Adjusting for confounding in a Cox proportional hazards model, we estimated one-year risks for ischemic stroke, transient ischemic attack (TIA) or systemic embolism, major or clinically relevant non-major bleeding; intracranial; gastrointestinal; and other bleeding. We censored at switch of treatment or 365 days of follow-up.ResultsWe included 30,820 treatment-naïve patients. Compared to warfarin, the adjusted hazard ratios (HR) for ischemic stroke, TIA or systemic embolism were 0.96 (95% CI 0.71-1.28) for dabigatran, 1.12 (95% CI 0.87-1.45) for rivaroxaban and 0.97 (95% CI 0.75-1.26) for apixaban. Corresponding hazard ratios for major or clinically relevant non-major bleeding were 0.73 (95% CI 0.62-0.86) for dabigatran, 0.97 (95% CI 0.84-1.12) for rivaroxaban and 0.71 (95% CI 0.62-0.82) for apixaban. Statistically significant differences of other safety outcomes compared to warfarin were fewer intracranial bleedings with dabigatran (HR 0.28, 95% CI 0.14-0.56), rivaroxaban (HR 0.40, 95% CI 0.23-0.69) and apixaban (HR 0.56, 95% CI 0.34-0.92); fewer gastrointestinal bleedings with apixaban (HR 0.70, 95% CI 0.52-0.93); and fewer other bleedings with dabigatran (HR 0.67, 95% CI 0.55-0.81) and apixaban (HR 0.70, 95% CI 0.59-0.83).ConclusionAfter 1 year follow-up in treatment-naïve patients initiating oral anticoagulation for non-valvular atrial fibrillation, all DOACs were similarly effective as warfarin in prevention of ischemic stroke, TIA or systemic embolism. Safety from bleedings was similar or better, including fewer intracranial bleedings with all direct oral anticoagulants, fewer gastrointestinal bleedings with apixaban and fewer other bleedings with dabigatran and apixaban.
| S-EPMC6709911 | biostudies-literature
Project description:Venous thromboembolism (VTE) is associated with inferior survival in cancer patients. The risk of VTE and its effect on survival in chronic lymphocytic leukemia (CLL) patients remains unclear. The present study investigated the impact of patient-related factors, CLL prognostic markers, and CLL treatment on the risk of VTE and assessed overall survival relative to VTE. All patients in the Danish National CLL Registry (2008-2015) were followed from the date of CLL diagnosis to death, VTE, emigration, or administrative censoring. Hazard ratios (HRs) were estimated using Cox models, and second primary cancers and anticoagulation treatment were included as time-varying exposures. During a median follow-up of 2.6 years, 92 VTEs occurred among 3609 CLL patients, corresponding to a total incidence rate of 8.2 VTEs per 1000 person-years (95% confidence interval [CI], 6.7-10.1). A history of VTE or second primary cancer was associated with HRs of VTE of 5.09 (95% CI, 2.82-9.17) and 3.72 (95% CI, 2.15-6.34), respectively, while ?2-microglobulin >4 mg/L, unmutated immunoglobulin HV and unfavorable cytogenetics had lower HRs. CLL patients with VTE had marginally higher mortality, which was most pronounced among patients <60 years of age (HR, 7.74; 95% CI, 2.12-28.29). Our findings suggest that markers of unfavorable CLL prognosis contribute to an increased risk of VTE; however, previous VTE or a second primary cancer is more strongly associated with the risk of VTE than any CLL-specific marker. Focusing attention on this preventable complication may improve survival in young CLL patients.
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Project description:This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60-1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71-1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key Points Rivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.
| S-EPMC10332896 | biostudies-literature
Project description:BackgroundAnticoagulation with low molecular weight heparin and vitamin K antagonists is the current standard of care (SOC) for venous thromboembolism (VTE) treatment and prevention. Although novel oral anti-coagulants (NOACs) have been compared with SOC in this indication, no head-to-head randomised controlled trials (RCTs) have directly compared NOACs. A systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of NOACs for the initial and long-term treatment of VTE.MethodsElectronic databases (accessed July 2014) were systematically searched to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban versus SOC. Eligible patients included adults with an objectively confirmed deep vein thrombosis (DVT), pulmonary embolism (PE) or both. A fixed-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as relative risks (RR) and 95% credible intervals (Crl).ResultsSix Phase III RCTs met criteria for inclusion: apixaban (one RCT; n = 5,395); rivaroxaban (two RCTs; n = 3,423/4,832); dabigatran (two RCTs; n = 2,539/2,568); edoxaban (one RCT; n = 8,240). There were no statistically significant differences between the NOACs with regard to the risk of 'VTE and VTE-related death. Apixaban treatment was associated with the most favourable safety profile of the NOACs, showing a statistically significantly reduced risk of 'major or clinically relevant non-major (CRNM) bleed' compared with rivaroxaban (0.47 [0.36, 0.61]), dabigatran (0.69 [0.51, 0.94]), and edoxaban (0.54 [0.41, 0.69]). Dabigatran was also associated with a significantly lower risk of 'major or CRNM bleed' compared with rivaroxaban (0.68 [0.53, 0.87]) and edoxaban (0.77 [0.60, 0.99]).ConclusionsIndirect comparisons showed statistically similar reductions in the risk of 'VTE or VTE-related death for all NOACs. In contrast, reductions in 'major or CRNM bleed' for initial/long-term treatment were significantly better with apixaban compared with all other NOACs, and with dabigatran compared with rivaroxaban and edoxaban. Results from the current analysis indicate that the NOACs offer clinical benefit over conventional therapy while highlighting relative differences in their bleeding profile.
| S-EPMC4696796 | biostudies-literature
Project description:BackgroundRivaroxaban was the first new oral anticoagulant approved for treatment of venous thromboembolism (VTE). Clinical trials have shown that rivaroxaban is noninferior to conventional anticoagulation for VTE in efficacy and safety. Increased fatigue after the initiation of rivaroxaban has been observed in clinical practice, but data on this potential side effect are lacking.ObjectiveThe study aimed to evaluate development of fatigue in patients treated for VTE, comparing rivaroxaban to other anticoagulants.MethodsPatients were prospectively recruited after a diagnosis of VTE. The Fatigue Questionnaire was used to determine the level of fatigue at baseline, at 3 weeks of treatment, and either at 1 month after the discontinuation of treatment if the treatment was discontinued after 3 months or at 6 months if treatment was continued beyond this time. Data was analyzed by a linear mixed model.ResultsA total of 126 patients were included. Mean age was 59 years; 77 (61%) were males. Fifty-seven patients (45%) were diagnosed with deep vein thrombosis, 48 (38%) with pulmonary embolism, and 21 (17%) with both. Predicted changes in fatigue scores from baseline to the last measurement were -0.007 and -2.49 for the rivaroxaban and the other-anticoagulants groups, respectively, neither of which were statistically significant. No difference was detected between rivaroxaban and the other-anticoagulants group at any time point, including subgroup analysis comparing over and under 6 months of treatment duration.ConclusionIn this small study, our results suggest no increase in the level of fatigue after the initiation of treatment with rivaroxaban for VTE.
| S-EPMC7292653 | biostudies-literature
Project description:BackgroundAtrial fibrillation is a major risk factor for stroke, which causes thousands of deaths and sequelae. It is recommended that atrial fibrillation patients at medium or high risk of stroke use an oral anticoagulant to reduce the risk of stroke. In the past few years, three new oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban, have been introduced in competition to the older oral anticoagulant warfarin.ObjectiveThe objective of this study was to evaluate the relative cost effectiveness of warfarin, dabigatran, rivaroxaban, and apixaban in a Norwegian setting.MethodsWe created a probabilistic decision-analytic Markov model to simulate the life of patients with atrial fibrillation. We performed several scenario analyses, including changing the switching age for dabigatran from 80 to 75 years old.ResultsAssuming the European Society of Cardiology guidance, sequential dabigatran (2 × 150 mg daily until 80 years old, 2 × 110 mg thereafter) seems to be the most cost-effective alternative for high-risk AF patients. For medium-risk patients, apixaban (2 × 5 mg daily) seems to be somewhat more effective than dabigatran, but dabigatran is still marginally the most cost-effective alternative. In scenario analyses reducing dabigatran from 2 × 150 mg to 2 × 110 mg at the age of 75 years (instead of at age 80), apixaban (2 × 5 mg daily) becomes the most cost-effective alternative for both risk groups.ConclusionWe have found apixaban or sequential dabigatran to be the alternatives most likely to be considered cost effective, depending on the switching age for dabigatran. These conclusions are highly sensitive to assumptions made in the analysis.
| S-EPMC4031399 | biostudies-literature
Project description:The effect of direct oral anticoagulants (DOAC) on laboratory tests dependent on the production of their targets, factor IIa and factor Xa, is a well-known problem and can cause both false positive and negative results. In particular, the situation in patients who develop lupus anticoagulant (LA) antibodies is highly complex. To evaluate the effectiveness of DOAC therapy in lupus-positive patients, 31 samples were enrolled in this retrospective study. All patient samples were spiked with three types of DOAC (dabigatran, DABI; rivaroxaban, RIVA; and apixaban, API) in a concentration that significantly influenced the screening test for LA and thus can mask the presence of LA. Subsequently, the DOAC was always unbound by the DOAC-Stop procedure. DOAC levels before and after binding were determined by functional assays, followed by liquid chromatography coupled with mass spectrometry (LC-MS) analysis. The determination of DOAC levels was performed by direct thrombin assay and determination of anti-Xa activity with specific calibration as functional tests for DABI and xabans (API and RIVA). To determine concentration levels of API, DABI, and RIVA, our in-house LC-MS method was used. The results of LA-positive samples show significant differences between functional tests and the LC-MS method both before and after DOAC binding. The acute findings of the presence of LA-type antibodies fundamentally affects the determination of DOAC by functional tests, and in this case, it is necessary to use LC-MS analysis to determine the true value. If patients treated with DOAC develop LA of medium and higher titers, we do not recommend checking DOAC levels with functional tests.
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