{"id":"7e22e5a9ded7","type":"article","url":"https://hartvaat.nl/2020/03/17/klinische-en-farmacologische-effecten-van-apixaban-dosisaanpassing-aristotle/","title":"Klinische en farmacologische effecten van apixaban-dosisaanpassing: ARISTOTLE","title_en":"Clinical and Pharmacological Effects of Apixaban Dose Adjustment in the ARISTOTLE Trial.","category":"atriumfibrilleren","category_label":"Atriumfibrilleren","professions":["apotheker","cardioloog"],"tags":[],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2019.12.060","source_url":"https://doi.org/10.1016/j.jacc.2019.12.060","authors":["Michel Zeitouni","Anna Giczewska","Renato D Lopes","Daniel M Wojdyla","Christina Christersson","Agneta Siegbahn","Raffaele De Caterina","Philippe Gabriel Steg","Christopher B Granger","Lars Wallentin","John H Alexander"],"significance":7,"published":"2020-03-17","source_date":"2020-03-17","image":"","kennis":["https://hartvaat.nl/kennis/atriumfibrilleren/af-bij-ouderen/","https://hartvaat.nl/kennis/antistolling/antistolling-bij-ckd/"],"congress":"","summary_en":"This ARISTOTLE analysis examined the clinical and pharmacological effects of apixaban dose adjustment, showing that appropriate dose reduction maintains efficacy while reducing bleeding in patients meeting dose-reduction criteria.","created":"2026-07-03T10:28:28Z","updated":"2026-07-03T13:27:39Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"ARISTOTLE analyse naar de klinische en farmacologische effecten van apixaban-dosisaanpassing bij AF. Relevant voor het dosisreductiebeleid.","abstract_original":"BACKGROUND: In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, patients with atrial fibrillation and ≥2 dose-adjustment criteria (age ≥80 years, weight ≤60 kg, or creatinine ≥1.5 mg/dl [133 μmol/l]) were randomized to receive apixaban 2.5 mg twice daily or warfarin. OBJECTIVES: The purpose of this study was to describe the effects of apixaban dose adjustment on clinical and pharmacological outcomes. METHODS: Patients receiving the correct dose of study drug were included (n = 18,073). The effect of apixaban 2.5 mg twice daily versus warfarin on population pharmacokinetics, D-dimer, prothrombin fragment 1 + 2 (PF1+2), and clinical outcomes was compared with the standard dose (5 mg twice daily). RESULTS: Patients receiving apixaban 2.5 mg twice daily exhibited lower apixaban exposure (median area under the concentration time curve at a steady state 2,720 ng/ml vs. 3,599 ng/ml; p < 0.0001) than those receiving the standard dose. In patients with ≥2 dose-adjustment criteria, reductions in D-dimers (p interaction = 0.20) and PF1+2 (p interaction = 0.55) were consistent with those observed in the standard-dose population. Patients with ≥2 dose-adjustment criteria (n = 751) were at higher risk for stroke/systemic embolism, major bleeding, and all-cause death than the standard-dose population (0 or 1 dose-adjustment criterion, n = 17,322). The effect of apixaban 2.5 mg twice daily versus warfarin in the ≥2 dose-adjustment criteria population was consistent with the standard dose in the reductions in stroke or systemic embolism (p interaction = 0.26), major bleeding (p interaction = 0.25), and death (p interaction = 0.72). CONCLUSIONS: Apixaban drug concentrations were lower in patients receiving 2.5 mg twice daily compared with 5 mg twice daily. However, the effects of apixaban dose adjustment to 2.5 mg versus warfarin were consistent for coagulation biomarkers and clinical outcomes, providing reassuring data on efficacy and safety. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984)."}