Comment on model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients
| Autor: | Hannah Mayer, Rolf Burghaus, Takahiko Tanigawa, Hans-Ulrich Siegmund, Jeffrey I. Weitz, Stefan Willmann, Liping Zhang, Gary Peters, Scott D. Berkowitz, Masato Kaneko |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
medicine.drug_mechanism_of_action Factor Xa Inhibitor Population 030204 cardiovascular system & hematology Thrombosis and Hemostasis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Edoxaban Internal medicine Atrial Fibrillation medicine Humans In patient 030212 general & internal medicine education Aged Prothrombin time Rivaroxaban education.field_of_study medicine.diagnostic_test business.industry Warfarin Anticoagulants Atrial fibrillation Hematology medicine.disease Stroke chemistry Meta-analysis Commentary Cardiology Apixaban business Factor Xa Inhibitors medicine.drug |
| Zdroj: | Blood Advances. 2:3193-3195 |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | The noninferiority of direct oral factor Xa (FXa) inhibitors (rivaroxaban, apixaban, and edoxaban) in treatment of atrial fibrillation were demonstrated compared with warfarin by several large clinical trials; however, subsequent meta-analyses reported a higher risk of major bleeding with rivaroxaban than with the other FXa inhibitors. In the present study, we first estimated the changes of prothrombin time (PT) in 5 randomized trials based on reported population pharmacokinetic and pharmacodynamic models and then carried out a model-based meta-analysis to obtain models describing the relationship between PT changes and the event rates of ischemic stroke/systemic embolism (SE) and of major bleeding. By using the models, we simulated the optimal therapeutic doses for each FXa inhibitor. It was suggested that dose reduction of rivaroxaban from the current 20 mg/d to 10 mg/d would decrease patient deaths from major bleeding (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.64-0.74) with little increase in those for ischemic stroke/SE (HR, 1.11; 95% CI, 1.07-1.20). The overall decrease in the mortality caused by both events was estimated as 5.81 per 10 000 patient-years (95% CI, 3.92-8.16), with an HR of 0.87 (95% CI, 0.83-0.91). For apixaban and edoxaban, no distinct change in the overall mortality was simulated by dose modification. This study suggested that the current dose of rivaroxaban might be excessive and would need to be reduced to decrease the excess risk of major bleeding. |
| Databáze: | OpenAIRE |
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