Original Articles
9 January 2024
Vol. 18 No. 1 (2024)
Assessment and predictors of inappropriate dose of direct oral anticoagulants
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
1096
Views
483
Downloads
137
HTML
Authors
Direct-Acting Oral Anticoagulants (DOACs) have revolutionized the management of Atrial Fibrillation (AF) and Venous Thromboembolism (VTE). However, recent audits reveal a significant burden of inappropriate dosages in the prescribing of direct-acting oral anticoagulants. Our aim is to identify the prevalence and predictors of such inappropriate dosing in our patients. This retrospective study was conducted from June 2016 to January 2018. Patients who received dabigatran, rivaroxaban, or apixaban for treatment of venous thromboembolism or atrial fibrillation were included. Appropriateness of direct-acting oral anticoagulants dosing was assessed using US Food and Drug Administration guidelines. Data was analyzed using IBM® SPSS Version 26. 337 patients were included, with a mean age of 62.9±18.7 years. The majority were female (196, 58.3%). Of the patients, 194 (57.6%) received apixaban, 99 (29.4%) received rivaroxaban, and 44 (13.1%) received dabigatran. A total of 242 (71.8%) patients were prescribed direct-acting oral anticoagulants appropriately. Under-dosing and over-dosing were identified in 74 (22%) and 21 (6.2%) patients, respectively. Predictors of inappropriate dosing were age greater than 75 years (OR: 2.76, 95% CI: 1.67-4.56, p<0.001) and creatinine clearance less than 50 ml/minute (OR: 0.38, 95% CI: 0.19-0.74, p: 0.005). Inappropriate dosing was significantly associated with mortality (p=0.010).One-third of our patients received an inappropriate dose of direct-acting oral anticoagulants, mostly from underdosing. Elderly age and low creatinine clearance are significant predictors of inappropriate dose administration.
Altmetrics
Downloads
Download data is not yet available.
Citations
Spahn G. Compliance with self-administration of heparin injections in outpatients. Eur J Trauma 2002;28:104-9. DOI: https://doi.org/10.1007/s00068-002-1176-1
Lee A, Crowther M. Practical issues with vitamin K antagonists: elevated INRs, low time-in-therapeutic range, and warfarin failure. J Thromb Thrombolysis 2011;31:249-58. DOI: https://doi.org/10.1007/s11239-011-0555-z
Sikorska J, Uprichard J. Direct oral anticoagulants: a quick guide. Eur Cardiol Rev 2017;12:40. DOI: https://doi.org/10.15420/ecr.2017:11:2
Bauer KA. Pros and cons of new oral anticoagulants. Hematology Am Soc Hematol Educ Program 2013;2013:464-70. DOI: https://doi.org/10.1182/asheducation-2013.1.464
Ruff CT, Giugliano RP, Braunwald E, 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. Lancet 2014;383:955-62. DOI: https://doi.org/10.1016/S0140-6736(13)62343-0
Bertoletti L, Gusto G, Khachatryan A, et al. Effectiveness and safety of oral anticoagulants in the treatment of acute
venous thromboembolism: a nationwide comparative cohort study in France. Thromb Haemost 2022;122:1384-96. DOI: https://doi.org/10.1055/a-1731-3922
Van Ganse E, Danchin N, Mahé I, et al. Comparative safety and effectiveness of oral anticoagulants in nonvalvular atrial fibrillation: the Naxos study. Stroke 2020;51:2066-75. DOI: https://doi.org/10.1161/STROKEAHA.120.028825
Chen A, Stecker E, Warden BA. Direct oral anticoagulant use: a practical guide to common clinical challenges. J Am Heart Assoc 2020;9:e017559. DOI: https://doi.org/10.1161/JAHA.120.017559
Trujillo-Santos J, Di Micco P, Dentali F, et al. Real-life treatment of venous thromboembolism with direct oral anticoagulants: the influence of recommended dosing and regimens. Thromb Haemost 2017;117:382-9. DOI: https://doi.org/10.1160/TH16-07-0494
Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association practical guide on the use of nonvitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021;23:1612-76. DOI: https://doi.org/10.1093/europace/euab157
Martin KA, Beyer-Westendorf J, Davidson BL, et al. Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost 2021;19:1874-82. DOI: https://doi.org/10.1111/jth.15358
Van der Horst SF, van Rein N, van Mens TE, et al. Inappropriate prescriptions of direct oral anticoagulants (DOACs) in hospitalized patients: A narrative review. Thromb Res 2023;231:135-140. DOI: https://doi.org/10.1016/j.thromres.2023.03.007
Ting C, Rhoten M, Dempsey J, et al. Evaluation of direct oral anticoagulant prescribing in patients with moderate to severe renal impairment. Clin Appl Thromb Hemost 2021;27:1076029620987900. DOI: https://doi.org/10.1177/1076029620987900
Yao X, Shah ND, Sangaralingham LR, et al. Non–vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol 2017;69: 2779-90. DOI: https://doi.org/10.1016/j.jacc.2017.03.600
Camm AJ, Cools F, Virdone S, et al. Mortality in patients with atrial fibrillation receiving nonrecommended doses of direct oral anticoagulants. J Am Coll Cardiol 2020;76:1425-36. DOI: https://doi.org/10.1016/j.jacc.2020.07.045
Pradaxa® (dabigatran etexilate capsules) (2021) [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield. Available at: https://docs.boehringeringelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf
Eliquis® (apixaban) (2021) [package insert]. Bristol-Myers Squibb Company, Princeton. Available at: https://packageinserts.bms.com/pi/pi_eliquis.pdf
Xarelto® (rivaroxaban) (2016) [package insert]. Janssen Ortho, LLC, Gurabo. Available at: https://www. accessdata.fda.gov/drugsatfda_docs/label/2016/202439s017lbl.pdf
Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864-70. DOI: https://doi.org/10.1001/jama.285.22.2864
Pisters R, Lane DA, Nieuwlaat R, et al. A novel userfriendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010;138:1093-100. DOI: https://doi.org/10.1378/chest.10-0134
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16:31-41. DOI: https://doi.org/10.1159/000180580
Viprey M, Jeannin R, Piriou V, et al. Prevalence of drugrelated problems associated with direct oral anticoagulants in hospitalized patients: a multicenter, cross-sectional study. J Clin Pharm Ther 2017;42:58-63. DOI: https://doi.org/10.1111/jcpt.12473
Ruiz Ortiz M, Muñiz J, Raña Míguez P, et al. Inappropriate doses of direct oral anticoagulants in realworld clinical practice: prevalence and associated factors. A subanalysis of the FANTASIIA Registry. Europace. 2018;20:1577-83. DOI: https://doi.org/10.1093/europace/eux316
Capiau A, De Backer T, Grymonprez M, et al. Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation according to the drug labelling and the EHRA Practical Guide. Int J Cardiol 2021;328:97-103. DOI: https://doi.org/10.1016/j.ijcard.2020.11.062
Sanghai S, Wong C, Wang Z, et al. Rates of potentially inappropriate dosing of direct-acting oral anticoagulants and associations with geriatric conditions among older patients with atrial fibrillation: the SAGE-AF study. J Am Heart Assoc 2020;9:e014108. DOI: https://doi.org/10.1161/JAHA.119.014108
Sen S, Dahlberg KW. Physician’s fear of anticoagulant therapy in nonvalvular atrial fibrillation. Am J Med Sci 2014;348:513-21. DOI: https://doi.org/10.1097/MAJ.0000000000000349
Moudallel S, Steurbaut S, Cornu P, Dupont A. Appropriateness of DOAC prescribing before and during hospital admission and analysis of determinants for inappropriate prescribing. Front Pharmacol 2018;9:1220. DOI: https://doi.org/10.3389/fphar.2018.01220
Elewa H, El-Makaty H, Ali Z. Appropriateness of dabigatran and rivaroxaban prescribing in Qatar: a 5- year experience. J Cardiovasc Pharmacol Ther 2018;23:155-61. DOI: https://doi.org/10.1177/1074248417731536
Sugrue A, Sanborn D, Amin M, et al. Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation. Am J Cardiol 2021;144:52-9. DOI: https://doi.org/10.1016/j.amjcard.2020.12.062
How to Cite
Assessment and predictors of inappropriate dose of direct oral anticoagulants. (2024). Italian Journal of Medicine, 18(1). https://doi.org/10.4081/itjm.2024.1679
Copyright (c) 2024 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- M. Dugnani, Dabigatran etexilate: a direct thrombin inhibitor , Italian Journal of Medicine: Vol. 1 No. 3 (2007)
- Luca Masotti, Mario Di Napoli, Walter Ageno, Davide Imberti, Daniel Godoy, Grazia Panigada, Niccolò Napoli, Giancarlo Landini, Roberto Cappelli, Ido Iori, Domenico Prisco, Giancarlo Agnelli, Efficacy and safety of new oral anticoagulants compared with warfarin in cardioembolic prophylaxis of patients with non valvular atrial fibrillation. More lights than shadows , Italian Journal of Medicine: Vol. 6 No. 3 (2012)
- Luca Masotti, Mario Di Napoli, Walter Ageno, Davide Imberti, Cecilia Becattini, Maurizio Paciaroni, Daniel Augustin Godoy, Roberto Cappelli, Giancarlo Landini, Grazia Panigada, Ido Iori, Domenico Prisco, Giancarlo Agnelli, Direct oral anticoagulants for secondary prevention in patients with non-valvular atrial fibrillation , Italian Journal of Medicine: Vol. 7 No. s8 (2013): The new oral anticoagulants in the Internal Medicine clinical practice
- Gianluca Airoldi, Mauro Campanini, Apixaban , Italian Journal of Medicine: Vol. 5 No. 2 (2011)
- Mauro Silingardi, New anticoagulant drugs versus warfarin in atrial fibrillation: economic evaluation and cost-effectiveness analysis , Italian Journal of Medicine: Vol. 7 No. s8 (2013): The new oral anticoagulants in the Internal Medicine clinical practice
- Davide Imberti, The treatment of venous thromboembolism with new oral anticoagulants , Italian Journal of Medicine: Vol. 7 No. s8 (2013): The new oral anticoagulants in the Internal Medicine clinical practice
- Gualtiero Palareti, Optimal duration of anticoagulant therapy in patients with venous thromboembolism , Italian Journal of Medicine: Vol. 12 No. 4 (2018)
- Ivan Gentile, Giancarlo Agnelli, Angelo Avogaro, Claudio Borghi, Alessia Ciancio, Ernesto Claar, Patrizio Pasqualetti, Pasquale Perrone Filardi, Pharmacological interactions in novel oral anticoagulants, statins, and hypertension drugs in patients treated with direct-acting antivirals for hepatitis C: a Delphi Consensus project , Italian Journal of Medicine: Vol. 18 No. 4 (2024)
- Andrea Donti, Patent foramen ovale and ischemic stroke: more shadows than lights? What the internist should know , Italian Journal of Medicine: Vol. 10 No. 3 (2016)
- Luca Masotti, Filippo Pieralli, Grazia Panigada, Francesco Corradi, Rino Migliacci, Salvatore Lenti, Alessandro Tafi, Carlo Nozzoli, Giancarlo Landini, for TUSCAN-PE Investigators, Characteristics and clinical management of acute pulmonary embolism in real world: findings from TUSCAN-PE study , Italian Journal of Medicine: Vol. 9 No. 2 (2015)
You may also start an advanced similarity search for this article.