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Periinterventional Management of Edoxaban in Major Procedures: Results from the DRESDEN NOAC REGISTRYFunding The DRESDEN NOAC REGISTRY is supported by the Gesellschaft für Technologie- und Wissenstransfer der Technischen Universität Dresden (GWT-TUD GmbH), Germany (sponsor) and by grants from Bayer AG, Boehringer Ingelheim, Daiichi Sankyo and Pfizer. All authors declare that these companies and institutions had no influence on the study design, conduct of the study, data collection, statistical analysis, or preparation of the manuscript.
Background Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism (VTE) treatment or stroke prevention in atrial fibrillation. Major surgical procedures are not uncommon in anticoagulated patients but data on perioperative edoxaban management are scarce.
Patients and Methods Using data from the prospective DRESDEN NOAC REGISTRY, we extracted data on major surgical procedures in edoxaban patients. Periinterventional edoxaban management patterns and rates of outcome events were evaluated until day 30 after procedure.
Results Between 2011 and 2021, 3,448 procedures were identified in edoxaban patients, including 287 (8.3%) major procedures. A scheduled interruption of edoxaban was observed in 284/287 major procedures (99%) with a total median edoxaban interruption time of 11.0 days (25–75th percentile: 5.0–18.0 days). Heparin bridging was documented in 183 procedures (46 prophylactic dosages, 111 intermediate and 26 therapeutic dosages). Overall, 7 (2.4%; 95% CI: 1.2–4.9%) major cardiovascular events (5 VTE, 2 arterial thromboembolic events) and 38 major bleedings (13.2%; 95% CI: 9.8–17.7%) were observed and 6 patients died (2.1%; 95% CI: 1.0–4.5%). Rates of major cardiovascular events with or without heparin bridging were comparable (4/137; 2.9%; 95% CI: 1.1–7.3% vs. 3/82; 3.7%; 95% CI: 1.3–10.2%). Major bleedings occurred numerically more frequent in patients receiving heparin bridging (23/137; 16.8%; 95% CI: 11.5–23.9%) versus procedures without heparin bridging (9/82; 11.0%; 95% CI: 5.9–19.6%).
Conclusion Within the limitations of our study design, real-world periprocedural edoxaban management seems effective and safe. Use of heparin bridging seems to have limited effects on reducing vascular events but may increase bleeding risk.
The DRESDEN NOAC REGISTRY is registered at ClinicalTrials.gov (NCT01588119). The study protocol of the Dresden NOAC registry was approved by the local ethics committee at the Technical University Dresden (AZ EK 349092011). All patients gave their written informed consent and signed a data protection waiver before enrolment.
J.B.-W. and L.T. conceived the present analysis and performed the statistical analyses. C.K. wrote the first draft of the manuscript. S.M., C.N. C.K. and J.B.-W. performed the central event adjudication. All authors contributed to the data collection and to the written presentation. All authors critically reviewed the manuscript and approved submission.
Received: 29 March 2023
Accepted: 26 June 2023
Article published online:
22 September 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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- 1 Douketis JD, Berger PB, Dunn AS. et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (6, Suppl): 299S-339S
- 2 Healey JS, Eikelboom J, Douketis J. et al; RE-LY Investigators. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation 2012; 126 (03) 343-348
- 3 Deerhake JP, Merz JC, Cooper JV, Eagle KA, Fay WP. The duration of anticoagulation bridging therapy in clinical practice may significantly exceed that observed in clinical trials. J Thromb Thrombolysis 2007; 23 (02) 107-113
- 4 Eljilany I, El-Bardissy A, Elewa H. The dilemma of peri-procedural warfarin management: a narrative review. Clin Appl Thromb Hemost 2021; 27: 10 760296211012093
- 5 Spyropoulos AC, Al-Badri A, Sherwood MW, Douketis JD. Periprocedural management of patients receiving a vitamin K antagonist or a direct oral anticoagulant requiring an elective procedure or surgery. J Thromb Haemost 2016; 14 (05) 875-885
- 6 Daiichi Sankyo UK. Lixiana 60 mg Film-Coated Tablets Summary of product characteristics 2022 [updated 22 Apr 2022]. Accessed August 10, 2023 at: https://www.medicines.org.uk/emc/product/6905/smpc
- 7 Steffel J, Collins R, Antz M. et al; External reviewers. 2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021; 23 (10) 1612-1676
- 8 Douketis JD, Healey JS, Brueckmann M. et al. Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure. Substudy of the RE-LY trial. Thromb Haemost 2015; 113 (03) 625-632
- 9 Steffel J. Non-vitamin K antagonist oral anticoagulants therapy for atrial fibrillation patients undergoing electrophysiologic procedures. Eur Heart J Suppl 2020; 22 (Suppl I): I32-I37
- 10 Colonna P, von Heymann C, Santamaria A. et al. Routine clinical practice in the periprocedural management of edoxaban therapy is associated with low risk of bleeding and thromboembolic complications: the prospective, observational, and multinational EMIT-AF/VTE study. Clin Cardiol 2020; 43 (07) 769-780
- 11 Unverdorben M, von Heymann C, Santamaria A. et al. Elderly patients with atrial fibrillation in routine clinical practice-peri-procedural management of edoxaban oral anticoagulation therapy is associated with a low risk of bleeding and thromboembolic complications: a subset analysis of the prospective, observational, multinational EMIT-AF study. BMC Cardiovasc Disord 2020; 20 (01) 504
- 12 Douketis JD, Spyropoulos AC, Spencer FA. et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e326S-e350S
- 13 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
- 14 Rodeghiero F, Tosetto A, Abshire T. et al; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8 (09) 2063-2065
- 15 Mehran R, Rao SV, Bhatt DL. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123 (23) 2736-2747
- 16 Schulman S, Angerås U, Bergqvist D, Eriksson B, Lassen MR, Fisher W. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 8 (01) 202-204
- 17 Beyer-Westendorf J, Gelbricht V, Förster K. et al. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur Heart J 2014; 35 (28) 1888-1896
- 18 Douketis JD, Spyropoulos AC, Duncan J. et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med 2019; 179 (11) 1469-1478