Periprocedural Direct Oral Anticoagulant Management: The RA-ACOD Prospective, Multicenter Real-World Registry

Abstract

Introduction There is scarce real-world experience regarding direct oral anticoagulants (DOACs) perioperative management. No study before has linked bridging therapy or DOAC-free time (pre-plus postoperative time without DOAC) with outcome. The aim of this study was to investigate real-world management and outcomes.

Methods RA-ACOD is a prospective, observational, multicenter registry of adult patients on DOAC treatment requiring surgery. Primary outcomes were thrombotic and hemorrhagic complications. Follow-up was immediate postoperative (24–48 hours) and 30 days. Statistics were performed using a univariate and multivariate analysis. Data are presented as odds ratios (ORs [95% confidence interval]).

Results From 26 Spanish hospitals, 901 patients were analyzed (53.5% major surgeries): 322 on apixaban, 304 on rivaroxaban, 267 on dabigatran, 8 on edoxaban. Fourteen (1.6%) patients suffered a thrombotic event, related to preoperative DOAC withdrawal (OR: 1.57 [1.03–2.4]) and DOAC-free time longer than 6 days (OR: 5.42 [1.18–26]). Minor bleeding events were described in 76 (8.4%) patients, with higher incidence for dabigatran (12.7%) versus other DOACs (6.6%). Major bleeding events occurred in 17 (1.9%) patients. Bridging therapy was used in 315 (35%) patients. It was associated with minor (OR: 2.57 [1.3–5.07]) and major (OR: 4.2 [1.4–12.3]) bleeding events, without decreasing thrombotic events.

Conclusion This study offers real-world data on perioperative DOAC management and outcomes in a large prospective sample size to date with a high percentage of major surgery. Short-term preprocedural DOAC interruption depending on the drug, hemorrhagic risk, and renal function, without bridging therapy and a reduced DOAC-free time, seems the safest practice.

Keywords

anticoagulant - dabigatran etexilate - apixaban - rivaroxaban - perioperative period

Authors' Contributions

R.F. and J.V.L. contributed toward: (1) conception and design, acquisition of data, and analysis and interpretation of data; (2) drafting the article and revising it critically for important intellectual content; (3) final approval of the version to be published; (4) agreement to be accountable for all aspects of the work thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. F.J.S., M.C.C., O.G.L., M.S.M., V.S., P.G., L.M.T., E.F.B., C.G.C., P.S., M.B., N.M., C.M.E., M.L., A.G.L., J.M., F.H., G.Y., R.R., B.C., E.D., B.T., A.P., M.A.V., J.C.A., and S.S. contributed toward: (1) acquisition of data; (2) revising the article critically for important intellectual content; (3) final approval of the version to be published; (4) agreement to be accountable for all aspects of the work thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. RA-ACOD investigators contributed toward: (1) acquisition of data; (2) final approval of the version to be published; (3) agreement to be accountable for all aspects of the work thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

^* A complete list of the RA-ACOD investigators is provided as [Supplementary Appendix].

• References

• 1 Eikelboom JW, Weitz JI. New anticoagulants. Circulation 2010; 121 (13) 1523-1532
• 2 Spahn DR, Beer JH, Borgeat A. , et al. NOACs in anesthesiology. Transfus Med Hemother 2019; 46 (04) 282-293
• 3 Douketis JD, Spyropoulos AC, Spencer FA. , et al. Perioperative management of antithrombotic therapy. Chest 2012; 141 (Suppl. 02) e326S-e350S
• 4 Keeling D, Tait RC, Watson H. ; British Committee of Standards for Haematology. Peri-operative management of anticoagulation and antiplatelet therapy. Br J Haematol 2016; 175 (04) 602-613
• 5 Kozek-Langenecker SA, Ahmed AB, Afshari A. , et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: first update 2016. Eur J Anaesthesiol 2017; 34 (06) 332-395
• 6 Ferrandis R, Castillo J, de Andrés J. , et al. The perioperative management of new direct oral anticoagulants: a question without answers. Thromb Haemost 2013; 110 (03) 515-522
• 7 Kozek-Langenecker SA, Afshari A, Albaladejo P. , et al; Guidelines from the European Society of Anaesthesiology. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30 (06) 270-382
• 8 Sié P, Samama CM, Godier A. , et al; Working Group on Perioperative Haemostasis; French Study Group on Thrombosis and Haemostasis. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis 2011; 104 (12) 669-676
• 9 Vivas D, Roldán I, Ferrandis R. , et al; Expert reviewers. Perioperative and periprocedural management of antithrombotic therapy: consensus document of SEC, SEDAR, SEACV, SECTCV, AEC, SECPRE, SEPD, SEGO, SEHH, SETH, SEMERGEN, SEMFYC, SEMG, SEMICYUC, SEMI, SEMES, SEPAR, SENEC, SEO, SEPA, SERVEI, SECOT and AEU. Rev Esp Cardiol (Engl Ed) 2018; 71 (07) 553-564
• 10 Steffel J, Verhamme P, Potpara TS. , et al; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16) 1330-1393
• 11 Shaw JR, Woodfine JD, Douketis J, Schulman S, Carrier M. Perioperative interruption of direct oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis. Res Pract Thromb Haemost 2018; 2 (02) 282-290
• 12 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
• 13 Sherwood MW, Douketis JD, Patel MR. , et al; ROCKET AF Investigators. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 2014; 129 (18) 1850-1859
• 14 Garcia D, Alexander JH, Wallentin L. , et al. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood 2014; 124 (25) 3692-3698
• 15 Douketis JD, Weitz JI, Murphy S, Deenadayalu N, Crompton AE. Perioperative adverse outcomes in patients with atrial fibrillation taking edoxaban or warfarin: analysis of the ENGAGE AF-TIMI 48 trial. J Am Coll Cardiol 2015; 65 (Suppl. 10) A2092
• 16 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
• 17 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
• 18 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
• 19 Jun M, Lix LM, Durand M. , et al; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study. BMJ 2017; 359: j4323
• 20 Vinogradova Y, Coupland C, Hill T, Hippisley-Cox J. Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care. BMJ 2018; 362: k2505
• 21 McIlmoyle K, Tran H. Perioperative management of oral anticoagulation. BJA Educ 2018; 18 (09) 259-264
• 22 Lijfering WM, Tichelaar YIGV. Direct oral anticoagulant use and risk of perioperative bleeding: evidence of absence or absence of evidence?. Res Pract Thromb Haemost 2018; 2 (02) 182-185
• 23 Tafur A, Douketis J. Perioperative management of anticoagulant and antiplatelet therapy. Heart 2018; 104 (17) 1461-1467
• 24 Douketis JD, Spyropoulos AC, Kaatz S. , et al; BRIDGE Investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015; 373 (09) 823-833
• 25 Daniels PR. Peri-procedural management of patients taking oral anticoagulants. BMJ 2015; 351: h2391
• 26 Chee YL, Crawford JC, Watson HG, Greaves M. ; British Committee for Standards in Haematology. Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. Br J Haematol 2008; 140 (05) 496-504