Ran Nissan1,2,3, Galia Spectre4,5, Avital Hershkovitz6,5, Hefziba Green7,5, Shai Shimony7, Lisa Cooper7, Sigal Nakav8, Tzippy Shochat9,5, Alon Grossman7,5, Shmuel Fuchs10,5. 1. Internal Medicine B, Beilinson Hospital, Rabin Medical Center, 39 Jabotinsky Street, 49100, Petah Tikva, Israel. ranni@clalit.org.il. 2. Pharmacy Services, Beilinson Hospital, Rabin Medical Center, 39 Jabotinsky Street, 49100, Petah Tikva, Israel. ranni@clalit.org.il. 3. Beit Rivka Geriatric Rehabilitation Center, 4 Hachamisha St, 49245, Petah Tikva, Israel. ranni@clalit.org.il. 4. Coagulation Unit, Institute of Hematology, Beilinson Hospital, Rabin Medical Center, 39 Jabotinsky Street, 49100, Petah Tikva, Israel. 5. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 6. Beit Rivka Geriatric Rehabilitation Center, 4 Hachamisha St, 49245, Petah Tikva, Israel. 7. Internal Medicine B, Beilinson Hospital, Rabin Medical Center, 39 Jabotinsky Street, 49100, Petah Tikva, Israel. 8. The Coagulation Laboratory, Beilinson Hospital, Rabin Medical Center, 39 Jabotinsky Street, 49100, Petah Tikva, Israel. 9. Bio-Statistical Unit, Rabin Medical Center, 49100, Petah Tikva, Israel. 10. Cardiology Institute, Assaf Harofe Medical Center, 70300, Zrifin, Israel.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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: ClinicalTrials.gov Identifier number NCT02623049.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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: ClinicalTrials.gov Identifier number NCT02623049.
Authors: Markus Gulilat; Anthony Tang; Steven E Gryn; Peter Leong-Sit; Allan C Skanes; Jeffrey E Alfonsi; George K Dresser; Sara L Henderson; Rhiannon V Rose; Daniel J Lizotte; Wendy A Teft; Ute I Schwarz; Rommel G Tirona; Richard B Kim Journal: Can J Cardiol Date: 2017-04-24 Impact factor: 5.223
Authors: Paul A Reilly; Thorsten Lehr; Sebastian Haertter; Stuart J Connolly; Salim Yusuf; John W Eikelboom; Michael D Ezekowitz; Gerhard Nehmiz; Susan Wang; Lars Wallentin Journal: J Am Coll Cardiol Date: 2013-09-27 Impact factor: 24.094
Authors: Christopher B Granger; John H Alexander; John J V McMurray; Renato D Lopes; Elaine M Hylek; Michael Hanna; Hussein R Al-Khalidi; Jack Ansell; Dan Atar; Alvaro Avezum; M Cecilia Bahit; Rafael Diaz; J Donald Easton; Justin A Ezekowitz; Greg Flaker; David Garcia; Margarida Geraldes; Bernard J Gersh; Sergey Golitsyn; Shinya Goto; Antonio G Hermosillo; Stefan H Hohnloser; John Horowitz; Puneet Mohan; Petr Jansky; Basil S Lewis; Jose Luis Lopez-Sendon; Prem Pais; Alexander Parkhomenko; Freek W A Verheugt; Jun Zhu; Lars Wallentin Journal: N Engl J Med Date: 2011-08-27 Impact factor: 91.245
Authors: Claes Held; Elaine M Hylek; John H Alexander; Michael Hanna; Renato D Lopes; Daniel M Wojdyla; Laine Thomas; Hussein Al-Khalidi; Marco Alings; Dennis Xavier; Jack Ansell; Shinya Goto; Witold Ruzyllo; Mårten Rosenqvist; Freek W A Verheugt; Jun Zhu; Christopher B Granger; Lars Wallentin Journal: Eur Heart J Date: 2014-12-12 Impact factor: 29.983