Apixaban concentrations in elderly NVAF patients: is less enough?

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Project Abstract

S. Sukumar1, M Gulilat, PhD2, B Linton3, S E. Gryn MD2, G K. Dresser MD2, J E. Alfonsi MD2, U I. Schwarz MD, PhD2, R B. Kim, MD2, JB. Schwartz, MD1

  1. University of California, San Francisco, San Francisco, CA, USA
  2. Schulich School of Medicine and Dentistry, Western University, London, ON Canada
  3. London Health Sciences Centre, London, ON Canada

Funding

Medical Student Training in Aging Research Program, Wolfe Medical Research Chair in Pharmacogenomics, Canadian Institutes of Health Research, Ontario Research FundResearch Excellence Grant

Background

Patients with nonvalvular atrial fibrillation (NVAF) often receive doses of direct-acting oral anticoagulants that differ from recommendations. The clinical impact is unknown. Our goal was to determine plasma apixaban concentrations in relation to dosing during routine clinical care of older patients with NVAF.

Methods

Plasma apixaban concentrations were determined by tandem mass spectrometry in older (65+y) outpatients with NVAF from an anticoagulation clinic. Concentrations were compared to 5- 95% peak and trough ranges seen in clinical trials and categorized as BELOW, WITHIN, or ABOVE range. Patient age, sex, weight, height, apixaban dose, strong P-gp/CYP3A4 inhibitor use, serum creatinine, and date/time of last apixaban dose were collected. Dosing was categorized as the same (CORRECT), higher-than (HIGH), or lower-than (LOW) recommended (recommended dosing is 5mg twice daily, reduced to 2.5mg twice daily with 2 of the following 3 criteria: age>80y, weight1.5 mg/dL, or strong P-gp/CYP3A4 inhibitor use).

Results 110 patients with NVAF were studied (mean±SD: age 80.4±7.8y). None received HIGH dosing. Of 42 patients dosed LOW, 1 was BELOW and 41 were WITHIN range. Of 68 dosed CORRECT, 1 was BELOW, 62 were WITHIN and 5 ABOVE range. Dosing regimen did not affect proportion of concentrations within range (Chi square, p=0.19).

Conclusions

Apixaban concentrations in older patients with NVAF receiving lower-than-recommended doses of apixaban were within 5-95% range of correctly dosed patients in clinical trials. Concentrations higher than those in clinical trials were seen with recommended dosing. Lower-than-recommended doses of apixaban may not be inappropriate in selected older patients with NVAF. The data suggest a clinical role for measuring apixaban concentrations or factor Xa inhibition.

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