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Association of Low Body Weight with Clinical Outcomes in Elderly Atrial Fibrillation Patients Receiving Apixaban—J-ELD AF Registry Subanalysis

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Abstract

Purpose

Although direct oral anticoagulants are effective and safe in preventing stroke in atrial fibrillation (AF) patients with low body weight, data remain limited in AF patients with extremely low body weight (<50 kg). We aimed to investigate the association of this body weight category with clinical outcomes in elderly AF patients receiving apixaban.

Methods

The J-ELD AF Registry is a large-scale, multicenter prospective observational study of Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban. The entire cohort (3025 patients from 110 institutions) was divided into three body weight subgroups: >60 kg (n = 1019, 33.7%), 50–60 kg (n = 1126, 37.2%), and <50 kg (n = 880, 29.1%).

Results

The event incidence rates (/100 person years) were 1.69, 1.82, and 1.23 for stroke or systemic embolism (P = 0.60); 1.37, 1.73, and 2.73 for bleeding requiring hospitalization (P = 0.154); 2.02, 2.67, and 4.92 for total death (P = 0.003); and 0.73, 0.95, and 1.23 for cardiovascular death (P = 0.57), respectively. After adjusting for confounders by Cox regression analysis, body weight <50 kg was not an independent risk for stroke or systemic embolism, bleeding requiring hospitalization, total death, or cardiovascular death.

Conclusions

The incidence of events in each body weight group was comparable for stroke or systemic embolism and bleeding requiring hospitalization, and body weight <50 kg might not be an independent risk for death in Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban.

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Availability of Data and Material

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Code Availability

Statistical analysis was performed using SAS Ver. 9.4 (SAS Institute Inc., Cray, NC).

References

  1. Heeringa J, van der Kuip DA, Hofman A, Kors JA, van Herpen G, Stricker BH, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27(8):949–53.

    Article  Google Scholar 

  2. Inoue H, Fujiki A, Origasa H, Ogawa S, Okumura K, Kubota I, et al. Prevalence of atrial fibrillation in the general population of Japan: an analysis based on periodic health examination. Int J Cardiol. 2009;137(2):102–7.

    Article  Google Scholar 

  3. Kodani E, Atarashi H. Prevalence of atrial fibrillation in Asia and the world. Journal of Arrhythmia. 2012;28(6):330–7.

    Article  Google Scholar 

  4. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest. 2010;137(2):263–72.

    Article  Google Scholar 

  5. Yamashita Y, Hamatani Y, Esato M, Chun YH, Tsuji H, Wada H, et al. Clinical characteristics and outcomes in extreme elderly (age >/= 85 years) Japanese patients with atrial fibrillation: the Fushimi AF Registry. Chest. 2016;149(2):401–12.

    Article  Google Scholar 

  6. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.

    Article  CAS  Google Scholar 

  7. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.

    Article  CAS  Google Scholar 

  8. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104.

    Article  CAS  Google Scholar 

  9. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. The Lancet. 2014;383(9921):955–62.

    Article  CAS  Google Scholar 

  10. Marzec LN, Wang J, Shah ND, Chan PS, Ting HH, Gosch KL, et al. Influence of direct oral anticoagulants on rates of oral anticoagulation for atrial fibrillation. J Am Coll Cardiol. 2017;69(20):2475–84.

    Article  CAS  Google Scholar 

  11. Yamashita Y, Uozumi R, Hamatani Y, Esato M, Chun YH, Tsuji H, et al. Current status and outcomes of direct oral anticoagulant use in real-world atrial fibrillation patients- Fushimi AF Registry. Circ J. 2017;81(9):1278–85.

    Article  Google Scholar 

  12. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;123(21):2363–72.

    Article  CAS  Google Scholar 

  13. Kato ET, Goto S, Giugliano RP. Overview of oral antithrombotic treatment in elderly patients with atrial fibrillation. Ageing Res Rev. 2019;49:115–24.

    Article  CAS  Google Scholar 

  14. Lee SR, Choi EK, Park CS, Han KD, Jung JH, Oh S, et al. Direct oral anticoagulants in patients with nonvalvular atrial fibrillation and low body weight. J Am Coll Cardiol. 2019;73(8):919–31.

    Article  CAS  Google Scholar 

  15. Upreti VV, Wang J, Barrett YC, Byon W, Boyd RA, Pursley J, et al. Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects. Br J Clin Pharmacol. 2013;76(6):908–16.

    Article  CAS  Google Scholar 

  16. Hohnloser SH, Fudim M, Alexander JH, Wojdyla DM, Ezekowitz JA, Hanna M, et al. Efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation and extremes in body weight. Circulation. 2019;139(20):2292–300.

    Article  CAS  Google Scholar 

  17. Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation - the J-ROCKET AF study. Circ J. 2012;76(9):2104–11.

    Article  CAS  Google Scholar 

  18. Hori M, Matsumoto M, Tanahashi N, Momomura S, Uchiyama S, Goto S, et al. Rivaroxaban vs. warfarin in Japanese patients with non-valvular atrial fibrillation in relation to age. Circ J. 2014;78(6):1349–56.

    Article  CAS  Google Scholar 

  19. Okumura K, Yamashita T, Suzuki S, Akao M, Investigators JEA. A multicenter prospective cohort study to investigate the effectiveness and safety of apixaban in Japanese elderly atrial fibrillation patients (J-ELD AF Registry). Clin Cardiol. 2020;43(3):251–9.

    Article  Google Scholar 

  20. Goto S, Zhu J, Liu L, Oh BH, Wojdyla DM, Aylward P, et al. Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Am Heart J. 2014;168(3):303–9.

    Article  CAS  Google Scholar 

  21. Halvorsen S, Atar D, Yang H, De Caterina R, Erol C, Garcia D, et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014;35(28):1864–72.

    Article  CAS  Google Scholar 

  22. Hamatani Y, Ogawa H, Uozumi R, Iguchi M, Yamashita Y, Esato M, et al. Low body weight is associated with the incidence of stroke in atrial fibrillation patients - insight from the Fushimi AF Registry. Circ J. 2015;79(5):1009–17.

    Article  Google Scholar 

  23. Ogawa S, Shinohara Y, Kanmuri K. Safety and efficacy of the oral direct factor xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation. -The ARISTOTLE-J study. Circ J. 2011;75(8):1852–9.

    Article  CAS  Google Scholar 

  24. Shimokawa H, Yamashita T, Uchiyama S, Kitazono T, Shimizu W, Ikeda T, et al. The EXPAND study: efficacy and safety of rivaroxaban in Japanese patients with non-valvular atrial fibrillation. Int J Cardiol. 2018;258:126–32.

    Article  Google Scholar 

  25. Collard RM, Boter H, Schoevers RA, Oude Voshaar RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012;60(8):1487–92.

    Article  Google Scholar 

  26. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.

    Article  CAS  Google Scholar 

  27. Watanabe D, Yoshida T, Watanabe Y, Yamada Y, Kimura M, Kyoto-Kameoka Study G. A U-shaped relationship between the prevalence of frailty and body mass index in community-dwelling Japanese older adults: the Kyoto-Kameoka study. J Clin Med. 2020;9(5). https://doi.org/10.3390/jcm9051367.

  28. Wei K, Nyunt MS, Gao Q, Wee SL, Yap KB, Ng TP. Association of frailty and malnutrition with long-term functional and mortality outcomes among community-dwelling older adults: results from the Singapore Longitudinal Aging Study 1. JAMA Netw Open. 2018;1(3):e180650.

    Article  Google Scholar 

  29. Suzuki S, Yamashita T, Akao M, Okumura K. investigators JEA. Clinical implications of assessment of apixaban levels in elderly atrial fibrillation patients: J-ELD AF registry sub-cohort analysis. Eur J Clin Pharmacol. 2020;76(8):1111–24.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank the J-ELD AF investigators for their support in patient registration and data collection. This study was conducted by the Cardiovascular Institute Academic Organization (CVI ARO), Tokyo, Japan, subsidized and funded by pharmaceutical and medical device companies.

Funding

Bristol-Myers Squibb K. K. provided monetary support for this study. This study was partially supported by the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development (AMED) (15656344 and JP17ek0210082). However, there was no conflict of interest between the study center and sponsor concerning the conduct of the study or study outcomes.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Takahide Kadosaka, Toshiyuki Nagai & Toshihisa Anzai

  2. Department of Cardiovascular Medicine, The Cardiovascular Institute, Tokyo, Japan

    Shinya Suzuki & Takeshi Yamashita

  3. Department of Cardiovascular Medicine, Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan

    Ichiro Sakuma

  4. Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Masaharu Akao

  5. Division of Cardiology, Saiseikai Kumamoto Hospital, Kumamoto, Japan

    Ken Okumura

Authors
  1. Takahide Kadosaka
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  2. Toshiyuki Nagai
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  3. Shinya Suzuki
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  4. Ichiro Sakuma
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  5. Masaharu Akao
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  6. Takeshi Yamashita
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  7. Toshihisa Anzai
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  8. Ken Okumura
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Consortia

on behalf of the J-ELD AF investigators

Contributions

Contributions by each author according to the Contributor Roles Taxonomy (CRediT; https://www.casrai.org/credit.html) are as follows:

Takahide Kadosaka: conceptualization, methodology, formal analysis, and writing—original draft

Toshiyuki Nagai: conceptualization, methodology, formal analysis, and writing—original draft

Shinya Suzuki: data curation, formal analysis, investigation, and writing—review and editing

Ichiro Sakuma: investigation and writing—review and editing

Masaharu Akao: investigation, project administration, and writing—review and editing

Takeshi Yamashita: funding acquisition, investigation, project administration, supervision, and writing—review and editing

Toshihisa Anzai: conceptualization, methodology, formal analysis, and writing—review and editing

Ken Okumura: funding acquisition, investigation, project administration, supervision, and writing—review and editing

Corresponding author

Correspondence to Toshiyuki Nagai.

Ethics declarations

Ethics Approval

This study was performed in conformity to the ethical norms based on the Declaration of Helsinki (revised in 2008) and Ethical Guidelines for Medical and Health Research Involving Human Subjects (Public Notice of the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health, Labor and Welfare in Japan, issued in 2014).

Consent to Participate

Prior to enrolment, the contents of the study were explained to the patients using explanatory documents and consent documents, and written consent was obtained. If a patient withdrew consent during the observation period, all existing data collected from the patient were discarded.

Conflict of Interest

Dr. Kadosaka reports no conflict. Dr. Nagai received honoraria from Daiichi Sankyo Co., Ltd., a clinical research grant from JSPS KAKENHI Grant-in-Aid for Scientific Research, and research grants from the Takeda Science Foundation, the Japan Foundation for Aging and Health, and the Uehara Memorial Foundation. Dr. Suzuki received research funding from Daiichi-Sankyo and Mitsubishi-Tanabe. Dr. Sakuma reports no conflict. Dr. Akao received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare, and Daiichi-Sankyo. Dr. Yamashita received lecture fees from Bristol Myers Squibb, Daiichi-Sankyo, Bayer, Pfizer, Ono Pharmaceutical, and Toa Eiyo and research funding from Bayer and Daiichi Sankyo. Dr. Anzai received honoraria from Daiichi Sankyo Co., Ltd., Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan Co., Ltd., Bayer Pharmaceuticals Co., Ltd., and Bristol-Myers Squibb Co., Ltd.; clinical research grants from the Japan Agency for Medical Research and Development and Daiichi Sankyo Co., Ltd.; and scholarship funds from Biotronik Japan Co., Ltd., Medtronic Japan Co., Ltd., Win International Co., Ltd., Medical System Network Co., Ltd., and Hokuyaku Takeyama Holdings, Inc. Dr. Okumura received lecture fees from Daiichi-Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, and Johnson & Johnson.

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Supplementary Information

Supplement Fig. 1

Efficacy and safety outcomes stratified by body weight and apixaban dose. BW, body weight; CI, confidence interval. (PPTX 3085 kb)

Supplement Table S1

(DOCX 24 kb)

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Kadosaka, T., Nagai, T., Suzuki, S. et al. Association of Low Body Weight with Clinical Outcomes in Elderly Atrial Fibrillation Patients Receiving Apixaban—J-ELD AF Registry Subanalysis. Cardiovasc Drugs Ther 36, 691–703 (2022). https://doi.org/10.1007/s10557-021-07180-4

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