Key result
Older adults with non-valvular atrial fibrillation receiving lower-than-recommended apixaban doses had a similar proportion of drug concentrations within expected ranges compared to those receiving recommended doses (p=0.35).
Why the study?
Lower than recommended doses of direct-acting oral anticoagulants are often prescribed to older adults with nonvalvular AF, but the consequences on plasma apixaban concentrations remained unclear.
Does lower than recommended dosing of apixaban result in subtherapeutic plasma concentrations in older adults with nonvalvular atrial fibrillation?
Cross-Sectional (n=110)
No
Does lower than recommended dosing of apixaban result in subtherapeutic plasma concentrations in older adults with nonvalvular atrial fibrillation?
Apixaban concentrations in older adults with NVAF seen in routine clinical care were higher than expected based on clinical trial data, suggesting that lower-than-recommended dosing may still achieve expected concentrations and highlighting a potential role for therapeutic monitoring.
Answers are grounded in this paper and cite their sources.
May support cautious dose individualization in older NVAF patients; leaves open need for prospective monitoring studies.
OBJECTIVES: Lower 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. DESIGN: Convenience sample of patients receiving anticoagulation during 2017. SETTING: Academic medical center. PARTICIPANTS: Stable adults older than 65 years with NVAF receiving apixaban on a chronic basis. MEASUREMENTS: Patient age, weight, creatinine, co-medications, and apixaban concentrations. RESULTS: A 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. CONCLUSIONS: Apixaban 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.
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Sukumar et al. (2019) conducted a cross-sectional in Non-valvular atrial fibrillation (n=110). Lower-than-recommended apixaban dosing vs. Recommended apixaban dosing was evaluated on Proportion of apixaban concentrations within or outside expected ranges (p=0.35). Older adults with non-valvular atrial fibrillation receiving lower-than-recommended apixaban doses had a similar proportion of drug concentrations within expected ranges compared to those receiving recommended doses (p=0.35).
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