Comment on model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients
Stefan WillmannLiping ZhangHannah MayerHans‐Ulrich SiegmundTakahiko TanigawaMasato KanekoGary PetersJeffrey I. WeitzScott D. BerkowitzRolf Burghaus
0
Citation
22
Reference
10
Related Paper
Abstract:
In a recent issue of Blood Advances, Yoshioka et al 1 performed a model-based meta-analysis (MBMA) to evaluate the optimal dose of rivaroxaban, apixaban, and edoxaban in patients with atrial fibrillation (AF).To develop the model, they used reported population pharmacokinetic (PK) and pharmacodynamic models to estimate time profiles of changes in the prothrombin time (PT) in 5 randomized controlled trials (RCTs) that evaluated the efficacy and safety of oral factor Xa (FXa) inhibitors in AF patients.After assay normalization, the authors calculated the model-based relationships between the simulated PT ratio profiles and the rates of ischemic stroke or systemic embolism and major bleeding, and used this information to determine the dose of each oral FXa inhibitor that would achieve minimal simulated mortality.Keywords:
Apixaban
Edoxaban
New, non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. These include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In the US, rivaroxaban and apixaban are licensed for thromboprophylaxis after elective hip or knee arthroplasty, and rivaroxaban and dabigatran are approved for treatment of venous thromboembolism. Dabigatran, rivaroxaban, and apixaban also are licensed for stroke prevention in eligible patients with atrial fibrillation. Designed to be given in fixed doses without routine coagulation monitoring, the NOACs are more convenient to administer than warfarin. Phase III clinical trials have shown that the NOACs are at least as effective as warfarin and are associated with less intracranial bleeding. This article compares the pharmacological properties of the NOACs with those of warfarin, describes the clinical trial data with the NOACs in the approved indications, outlines the unmet medical needs that the NOACs address, highlights the potential limitations of the NOACs, and provides guidance on the optimal use of the NOACs.
Apixaban
Edoxaban
Direct thrombin inhibitor
Vitamin K antagonist
Cite
Citations (18)
Edoxaban
Apixaban
Stroke
Cite
Citations (0)
Abstract: Three factor Xa inhibitors have been studied in the treatment of venous thromboembolism, both for acute therapy and as extended therapy to prevent recurrent events. Rivaroxaban, apixaban, and edoxaban have all proven to be effective in Phase III clinical trials for this indication when compared to current standard of therapy with similar or less bleeding. Nevertheless, the agents all offer different pharmacological profiles, which have an impact on patient selection and potential advantages in clinical practice. Keywords: anti-Xa inhibitors, apixaban, edoxaban, rivaroxaban, venous thromboembolism
Edoxaban
Apixaban
Cite
Citations (44)
Traditionally, warfarin has been used to prevent stroke in patients with atrial fibrillation (AF), but data from large, multinational, prospective, randomized studies suggest that novel oral anticoagulants (NOACs) may be suitable alternatives.These include the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban.These data showed that dabigatran 150 mg twice daily was more effective at preventing stroke than warfarin, with similar rates of major bleeding, while rivaroxaban 20 mg once daily was noninferior to warfarin, with no difference in major bleeding rates.In addition, apixaban 5 mg twice daily was shown to be superior to warfarin for preventing stroke, with lower bleeding rates.Currently, edoxaban is still in clinical trials.NOACs offer more predictable anticoagulant effects than warfarin and do not require regular monitoring; however, different NOACs are associated with varied drug interactions and limitations related to use in certain patient populations.Overall, the clinical data suggest that these novel agents will offer new options for stroke prevention in patients with AF.
Edoxaban
Apixaban
Stroke
Cite
Citations (16)
Only anticoagulation has been shown to reduce atrial fibrillation-related deaths.Vitamin K antagonists are difficult to use due to their narrow therapeutic range, unpredictable response, requirement for frequent coagulation monitoring, frequent dose adjustment, slow onset-offset, and numerous drug-drug and drug-food interactions.New oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, and apixaban have been developed and are available in Korea, and edoxaban was shown to be effective and safe, also.NOACs showed better pharmacodynamics with predictable serum concentrations and effects, and no requirement for coagulation monitoring.These drugs have been shown to be more effective and safer than warfarin for prevention of stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation.Broad, appropriate, and aggressive use of NOACs would improve the results of treatment in patients with nonvalvular atrial fibrillation in Korea.(Korean
Edoxaban
Apixaban
Stroke
Oral anticoagulant
Cite
Citations (0)
The monitoring of the effects of direct oral anticoagulants may be beneficial during emergencies and adverse events. We aimed to explore direct oral anticoagulant monitoring in "real-world" settings, in which monitoring methods are limited and loading time can be estimated based on only patient reports.In 164 patients, plasma anti-Xa activity was assessed using a STA®-Liquid Anti-Xa reagent (Diagnostica Stago, Asnieres, France), and prothrombin time was measured using HemosIL® RecombiPlasTin 2G (Instrumentation Laboratory, Bedford, MA, USA). The loading time was calculated according to the previous dosing time reported by the patient. In the clinic setting, rivaroxaban and apixaban were administered to 103 patients with atrial fibrillation and a blood sample was tested once during a clinic visit. In the hospitalization setting, edoxaban was administered to 61 patients undergoing arthroplasty for prophylaxis of a venous thrombosis and blood samples were tested 3 and 18 h after the last intake.Plasma Xa activity in the clinical setting ranged widely (rivaroxaban: 1.1-424.4 ng/mL, apixaban: 15.4-469.2 ng/mL) during the 11.7 ± 7.0 h following the previous dose. The values varied over a wide range (up to a factor of 2) at the same loading time, especially around the peak period. The plasma anti-Xa activity of rivaroxaban and apixaban showed linear correlations with prothrombin time (R2 = 0.828 and 0.717, respectively). Edoxaban administration prolonged the prothrombin time by only 1.6 ± 1.1 s from the trough to the peak, to a degree that was negatively correlated with age, but not with plasma creatinine level, creatinine clearance, or body mass index.In real-world settings, plasma anti-Xa monitoring should be interpreted considering the wide variations in data, reflecting the variability in patient-reported loading time and interpatient variability.
Apixaban
Edoxaban
Prothrombin time
Oral anticoagulant
Major bleeding
Cite
Citations (11)
Apixaban
Edoxaban
Stroke
Cite
Citations (5)
Apixaban
Edoxaban
Cite
Citations (11)
Apixaban
Edoxaban
Stroke
Cite
Citations (26)
Warfarin has remained the mainstay of stroke prevention in atrial fibrillation for the past 60 years. Recently, two new groups of novel oral anticoagulants- direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) have shown promising results in well conducted clinical trials in terms of efficacy, safety and convenience of usage. However, in real world practice these novel agents come with their share of side effects and drawbacks which the prescribing physician must be aware about. In this review we discuss the role of these novel agents in real world clinical practice – their advantages, disadvantages and future directions. Keywords: Apixaban, dabigatran, edoxaban, novel anticoagulants, rivaroxaban, warfarin.
Edoxaban
Apixaban
Stroke
Cite
Citations (2)