Abstract
Background
Direct oral anticoagulants (DOACs) have become favorable choices for anticoagulation due to their fixed-dose schedule, limited need for monitoring, and non-inferiority or superiority to warfarin. DOACs are currently not recommended in patients with a body weight ≥ 120 kg or body mass index ≥ 40 kg/m2 due to limited data regarding safety and efficacy.
Objective
The aim of this study was to compare the safety and efficacy of DOACs in patients with nonvalvular atrial fibrillation (NVAF) and weighing ≥ 120 kg with those weighing < 120 kg.
Methods
A single-center, retrospective study was conducted in patients weighing ≥ 120 kg who received either apixaban, dabigatran, or rivaroxaban for stroke risk reduction in NVAF, and matched to patients who weighed < 120 kg. The primary outcome was the incidence of stroke, deep vein thrombosis, pulmonary embolism, or myocardial infarction, while the safety outcome was the incidence of major or clinically relevant non-major bleeding based on the International Society on Thrombosis and Haemostasis (ISTH) definitions.
Results
A total of 318 patients weighing ≥ 120 kg with NVAF and meeting the inclusion criteria were evaluated and matched with 318 patients weighing < 120 kg. The primary outcome occurred in 2.5% of patients in the ≥ 120 kg group and in 3.1% of patients in the < 120 kg group (p = 0.632). The safety outcome occurred in 5.3% and 6.6% of patients in these respective groups (p = 0.503).
Conclusion
Apixaban, dabigatran, or rivaroxaban may be well-tolerated and effective anticoagulant options in patients with NVAF weighing ≥ 120 kg.
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References
Barnes GD, Lucas E, Alexander GC, Golberger ZD. National trends in ambulatory oral anticoagulant use. Am J Med. 2015;128(12):1300–5.
January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation. 2019;140(2):125–51.
Granger CB, Alexander JH, McMurray JJV, 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.
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.
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.
Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United States, 2015–2016. NCHS Data Brief. 2017;288:1–8.
Martin K, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14(6):1308–13.
Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015;13(11):2119–26.
Piran S, Traquair H, Chan N, Bhagirath V, Schulman S. Peak plasma concentration of direct oral anticoagulants in obese patients weighing over 120 kilograms: a retrospective study. Res Pract Thromb Haemost. 2018;2(4):684–8.
Speed V, Green B, Roberts LN, Woolcombe S, Bartoli-Abdou J, Barsam S, et al. Fixed dose rivaroxaban can be used in extremed of bodyweight: a population pharmacokinetic analysis. J Thromb Haemost. 2020;18(9):2296–307.
Kido K, Ngorsuraches S. Comparing the efficacy and safety of direct oral anticoagulants with warfarin in the morbidly obese population with atrial fibrillation. Ann Pharmacother. 2019;53(2):165–70.
Patil T, Lebrecht M. A single center retrospective cohort study evaluating use of direct oral anticoagulants (DOACs) in morbidly obese veteran population. Thromb Res. 2020;192:124–30.
Kalani C, Awudi E, Alexander T, Udeani G, Surani S. Evaluation of the efficacy of direct oral anticoagulants (DOACs) in comparison to warfarin in morbidly obese patients. Hos Pract. 2019;47(4):181–5.
Perales IJ, Agustin KS, DeAngelo J, Campbell AM. Rivaroxaban versus warfarin for stroke prevention and venous thromboembolism treatment in extreme obesity and high body weight. Ann Pharmacother. 2020;54(4):344–50.
Kushnir M, Choi Y, Eisenburg R, Rao D, Tolu S, Gao J, et al. Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single, retrospective analysis of chart data. Lancet Hematol. 2019;6(7):359–65.
Lucijanic M, Jurin I, Jurinc H, Lucijanic T, Starcevic B, Skelin M, et al. Patients with higher body mass index treated with direct/novel oral anticoagulants (DOAC/NOAC) for atrial fibrillation experience worse clinical outcomes. Int J Cardiol. 2020;301:90–5.
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.
Deitelzweig S, Keshishian A, Kang A, Dhamane AD, Luo X, Li X, et al. Effectiveness and safety of oral anticoagulants among NVAF patients with obesity: Insights from the ARISTOPHANES study. J Clin Med. 2020;9(6):1633.
Acknowledgements
The authors are grateful for the assistance of Erin Weeda in study design and statistical analysis ideas and would like to recognize Jessica Crane, Casey Cummings, and Anna Kroninger for assistance with data collection.
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This research was not supported by any funding.
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Eryne Wiethorn, Carolyn Magee Bell, and Barbara Wiggins have no conflicts of interest to disclose.
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Approval was obtained from the Ethics Committee of the Medical University of South Carolina. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.
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This study was retrospective, therefore consent to participate was not required.
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This study was retrospective, therefore consent to publish was not required.
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The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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All code for data cleaning and analysis associated with the current study is available from the corresponding author upon reasonable request.
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Wiethorn, E.E., Bell, C.M. & Wiggins, B.S. Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Weighing ≥ 120 Kilograms versus 60–120 Kilograms. Am J Cardiovasc Drugs 21, 545–551 (2021). https://doi.org/10.1007/s40256-021-00470-0
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DOI: https://doi.org/10.1007/s40256-021-00470-0