Drugs & Aging

, Volume 36, Issue 2, pp 165–177 | Cite as

Apixaban Levels in Octogenarian Patients with Non-valvular Atrial Fibrillation

  • Ran NissanEmail author
  • Galia Spectre
  • Avital Hershkovitz
  • Hefziba Green
  • Shai Shimony
  • Lisa Cooper
  • Sigal Nakav
  • Tzippy Shochat
  • Alon Grossman
  • Shmuel Fuchs
Original Research Article



There is a paucity of data on apixaban levels among octogenarians with non-valvular atrial fibrillation (NVAF). We aimed to compare apixaban levels between octogenarians (with and without dose reduction) and younger patients, to assess the frequency of high and above-range drug levels.


A cross-sectional, prospective study of 80 patients treated with apixaban for NVAF was conducted. Apixaban levels were compared among octogenarians treated with 5 mg twice daily (bid), octogenarians with appropriately reduced dose (2.5 mg bid), octogenarians with inappropriately reduced dose and younger patients (age < 70 years). Trough and peak levels were measured by a chromogenic assay calibrated for apixaban and compared to predicted manufacturer levels.


A significant proportion of the cohort had above-range trough [n = 11 (13.8%)] and peak [n = 16 (20%)] levels, especially octogenarians with the 5-mg bid dosage [n = 6 (30%) for trough and n = 8 (40%) for peak]. No significant differences were found in the trough or peak geometric mean (GM) levels among the groups, apart from the peak GM levels between the 5-mg octogenarian group and the other two 2.5-mg bid octogenarian groups (p = 0.0004). The frequency of apixaban peak levels within the upper quartile was significantly higher in the 5-mg octogenarian group compared to the other groups [n = 12 (60%) of measurements, p = 0.019), whereas trough levels were comparable between groups.


High and above-range peak apixaban steady-state levels are highly prevalent in octogenarians receiving the appropriate dosage of 5 mg bid for NVAF stroke prevention. Age above 80 strongly affects apixaban levels.

Trial Registration Identifier number NCT02623049.



Angiotensin-converting enzyme inhibitor


Atrial fibrillation


Anti-factor Xa activity


Alanine aminotransferase


Analysis of covariance


Analysis of variance


Activated partial thromboplastin time


Angiotensin receptor blocker


Aspartate aminotransferase


Area under the curve


Body mass index


Twice a day


Chronic heart failure


Chronic kidney disease


Creatinine clearance


Coefficient of variation


Cytochrome P450 3A4


Direct oral anticoagulant


Food and Drug Administration


Geometric mean


International normalized ratio


International Society on Thrombosis and Haemostasis


Non-valvular atrial fibrillation


Optical density generated per minute




Serum creatinine


Standard deviation


Time to reach maximum (peak) plasma concentration


Upper limit of normal


Factor Xa



The authors would like to thank Maya Arlyuk, Irina Genin and Keren Yoskovitch for their technical support during this study.

Author contributions

RN designed the study, collected data and wrote the manuscript; GS designed the study, recruited patients and wrote the manuscript; AH recruited patients and reviewed the manuscript; HG recruited patients and reviewed the manuscript; SS recruited patients; LC recruited patients; SN performed drug-level analysis and reviewed the manuscript; TS performed the statistical analysis; AG reviewed the manuscript; SF designed the study, recruited patients and wrote the manuscript.

Compliance with Ethical Standards

Conflict of interest

Dr. Galia Spectre reports receiving lecture fees (honorarium) from Pfizer. Ran Nissan, Avital Hershkovitz, Hefziba Green, Shai Shimony, Lisa Cooper, Sigal Nakav, Tzippy Shochat, Alon Grossman and Shmuel Fuchs declare that they have no potential conflicts of interest that might be relevant to the contents of this article.


Pfizer pharmaceuticals funded the study (unrestricted grant).

Ethical approval

Rabin Medical Center Institutional Review Board (#0590-15) approved the study.

Informed consent

The patients agreed to participate in the research and signed informed consent for study participation.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Internal Medicine BBeilinson Hospital, Rabin Medical CenterPetah TikvaIsrael
  2. 2.Pharmacy ServicesBeilinson Hospital, Rabin Medical CenterPetah TikvaIsrael
  3. 3.Beit Rivka Geriatric Rehabilitation CenterPetah TikvaIsrael
  4. 4.Coagulation UnitInstitute of Hematology, Beilinson Hospital, Rabin Medical CenterPetah TikvaIsrael
  5. 5.The Coagulation LaboratoryBeilinson Hospital, Rabin Medical CenterPetah TikvaIsrael
  6. 6.Bio-Statistical UnitRabin Medical CenterPetah TikvaIsrael
  7. 7.Cardiology Institute, Assaf Harofe Medical CenterZrifinIsrael
  8. 8.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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