학술논문

Apixaban Concentrations with Lower than Recommended Dosing in Older Adults with Atrial Fibrillation
Document Type
article
Source
Journal of the American Geriatrics Society. 67(9)
Subject
Pharmacology and Pharmaceutical Sciences
Biomedical and Clinical Sciences
Clinical Research
Heart Disease
Clinical Trials and Supportive Activities
Aging
Cardiovascular
6.1 Pharmaceuticals
Evaluation of treatments and therapeutic interventions
Aged
Aged
80 and over
Anticoagulants
Atrial Fibrillation
Dose-Response Relationship
Drug
Female
Humans
Male
Pyrazoles
Pyridones
apixaban
direct-acting oral anticoagulant
nonvalvular atrial fibrillation
dosing accuracy
Medical and Health Sciences
Geriatrics
Biomedical and clinical sciences
Health sciences
Psychology
Language
Abstract
ObjectivesLower than recommended doses of direct-acting oral anticoagulants are often prescribed to older adults with nonvalvular atrial fibrillation (NVAF). Our goal was to determine the consequences of lower than recommended dosing on plasma apixaban concentrations during the clinical care of older adults with NVAF.DesignConvenience sample of patients receiving anticoagulation during 2017.SettingAcademic medical center.ParticipantsStable adults older than 65 years with NVAF receiving apixaban on a chronic basis.MeasurementsPatient age, weight, creatinine, co-medications, and apixaban concentrations.ResultsA total of 110 older adults with NVAF (mean age = 80.4 y; range = 66-100 y with 45% women) were studied. Overall, 48 patients received recommended dosing of 5 mg twice/day, and 42 received lower than recommended dosing. One patient in each category had concentrations below the expected 5% to 95% range at time of peak concentrations. Differences in proportion of apixaban concentrations within or outside expected ranges were not significant between patients receiving lower than recommended doses and those dosed as recommended at 5 mg twice/day (P = .35). However, in patients dosed as recommended with 5 mg twice/day, four had concentrations above the 5% to 95% range for peak levels expected at 3 to 4 hours after dosing; in two, this occurred around the midpoint of the dosing interval. Twenty patients received 2.5 mg twice/day as recommended. One-third had apixaban concentrations higher than expected peak concentrations compared with the clinical trials, and more than two-thirds had levels above the reported median for peak concentrations.ConclusionsApixaban concentrations in older adults with NVAF seen clinically were higher than expected based on clinical trial data. The findings raise questions about the optimal dosing of apixaban in older adults with NVAF encountered outside of clinical trials and suggest a role for the monitoring of apixaban concentrations during care of patients that differ from those in randomized trials or when considering dosing outside of published guidelines. J Am Geriatr Soc 67:1902-1906, 2019.