Download PDF
Thromb Haemost 2018; 118(06): 1001-1008
DOI: 10.1055/s-0038-1645856
Coagulation and Fibrinolysis
Schattauer GmbH Stuttgart

Peri-operative Adverse Outcomes in Patients with Atrial Fibrillation Taking Warfarin or Edoxaban: Analysis of the ENGAGE AF-TIMI 48 Trial

James D. Douketis
1   Department of Medicine, McMaster University, Hamilton, Canada
,
Sabina A. Murphy
2   Department of Medicine, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, United States
,
Elliott M. Antman
2   Department of Medicine, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, United States
,
Laura T. Grip
2   Department of Medicine, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, United States
,
Michele F. Mercuri
3   Daiichi-Sankyo Pharma Development, Basking Ridge, New Jersey, United States
,
Christian T. Ruff
2   Department of Medicine, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, United States
,
Jeffrey I. Weitz
1   Department of Medicine, McMaster University, Hamilton, Canada
4   Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada
,
Eugene Braunwald
2   Department of Medicine, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, United States
,
Robert P. Giugliano
2   Department of Medicine, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts, United States
› Author Affiliations
Further Information

Publication History

08 January 2018

21 March 2018

Publication Date:
03 May 2018 (online)

    Permissions and Reprints

Abstract

Background Peri-operative management of anticoagulated patients with atrial fibrillation (AF) is challenging. To gain information on the peri-operative management of edoxaban, we compared outcomes in patients on warfarin or edoxaban enrolled in ENGAGE AF-TIMI 48 who underwent a surgery or invasive procedure.

Methods Data from patients undergoing their first surgery/procedure were analysed and results compared by anticoagulant (warfarin vs. higher- or lower-dose edoxaban regimen [HDER and LDER, respectively]). Patients were classified by procedural management: anticoagulant interrupted (last dose 4–10 days pre-procedure) or anticoagulant continued (last dose ≤ 3 days pre-procedure). Stroke/systemic embolism (SSE), major bleeding (MB), MB or clinically relevant non-MB (CRNMB) and death were assessed from 7 days pre- until 30 days post-procedure. The chi-square test was used to compare outcomes across treatment groups.

Results A total of 7,193 patients (34%) underwent surgery/procedure: 3,116 had anticoagulant interrupted, 4,077 had anticoagulant continued. Among patients on warfarin, HDER and LDER who had anticoagulant interrupted, rates of SSE were 0.6, 0.5 and 0.9% (p = 0.53), rates of MB were 1.0, 1.2 and 1.1% (p = 0.94) and rates of MB or CRNMB were 3.9, 4.2 and 3.6% (p = 0.78); among patients on warfarin, HDER and LDER who had anticoagulant continued, rates of SSE were 1.1, 0.7 and 0.9% (p = 0.51), rates of MB were 3.6, 2.6 and 2.4% (p = 0.13) and rates of MB or CRNMB were 8.5, 7.9 and 6.6% (p = 0.17).

Conclusion In patients requiring surgery/procedure in ENGAGE AF-TIMI 48, peri-operative rates of SSE, MB and death were not significantly different in patients who received edoxaban or warfarin.

Keywords

clinical trials - oral anticoagulants - stroke/prevention - bleeding - warfarin - edoxaban

Supplementary Material

 

  • References

  • 1 Büller HR. Edoxaban versus warfarin for venous thromboembolism. N Engl J Med 2014; 370 (01) 80-81
    CrossrefPubMedGoogle Scholar
  • 2 Giugliano RP, Ruff CT, Braunwald E. , et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
    CrossrefPubMedGoogle Scholar
  • 3 Palareti G, Poli D. The challenges and limitations of widespread direct oral anticoagulant treatment: practical suggestions for their best use. Expert Rev Cardiovasc Ther 2016; 14 (02) 163-176
    CrossrefPubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 Douketis JD, Syed S, Schulman S. Periprocedural management of direct oral anticoagulants: comment on the 2015 American Society of Regional Anesthesia and Pain Medicine Guidelines. Reg Anesth Pain Med 2016; 41 (02) 127-129
    CrossrefPubMedGoogle Scholar
  • 6 Spyropoulos AC, Al-Badri A, Sherwood MW, Douketis JD. To measure or not to measure direct oral anticoagulants before surgery or invasive procedures: comment. J Thromb Haemost 2016; 14 (12) 2556-2559
    CrossrefPubMedGoogle Scholar
  • 7 Douketis JD. Pharmacologic properties of the new oral anticoagulants: a clinician-oriented review with a focus on perioperative management. Curr Pharm Des 2010; 16 (31) 3436-3441
    CrossrefPubMedGoogle Scholar
  • 8 Partida RA, Giugliano RP. Edoxaban: pharmacological principles, preclinical and early-phase clinical testing. Future Cardiol 2011; 7 (04) 459-470
    CrossrefPubMedGoogle Scholar
  • 9 Mendell J, Chen S, He L, Desai M, Parasramupria DA. The effect of rifampin on the pharmacokinetics of edoxaban in healthy adults. Clin Drug Investig 2015; 35 (07) 447-453
    CrossrefPubMedGoogle Scholar
  • 10 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285 (22) 2864-2870
    CrossrefPubMedGoogle Scholar
  • 11 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138 (05) 1093-1100
    CrossrefPubMedGoogle Scholar
  • 12 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 (02) 263-272
    CrossrefPubMedGoogle Scholar
  • 13 Spyropoulos AC, Douketis JD, Gerotziafas G, Kaatz S, Ortel TL, Schulman S. ; Subcommittee on Control of Anticoagulation of the SSC of the ISTH. Periprocedural antithrombotic and bridging therapy: recommendations for standardized reporting in patients with arterial indications for chronic oral anticoagulant therapy. J Thromb Haemost 2012; 10 (04) 692-694
    CrossrefPubMedGoogle Scholar
  • 14 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
    CrossrefPubMedGoogle Scholar
  • 15 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-50S
    CrossrefPubMedGoogle Scholar
  • 16 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 ed. Chest 2008; 133 (6 Suppl): 299S-339S
    CrossrefPubMedGoogle Scholar
  • 17 Connolly SJ, Milling Jr TJ, Eikelboom JW. , et al; ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016; 375 (12) 1131-1141
    CrossrefPubMedGoogle Scholar
  • 18 Ruff CT, Giugliano RP, Antman EM. Management of bleeding with non-vitamin K antagonist oral anticoagulants in the era of specific reversal agents. Circulation 2016; 134 (03) 248-261
    CrossrefPubMedGoogle Scholar
  • 19 Jamula E, Anderson J, Douketis JD. Safety of continuing warfarin therapy during cataract surgery: a systematic review and meta-analysis. Thromb Res 2009; 124 (03) 292-299
    CrossrefPubMedGoogle Scholar
  • 20 Jamula E, Douketis JD, Schulman S. Perioperative anticoagulation in patients having implantation of a cardiac pacemaker or defibrillator: a systematic review and practical management guide. J Thromb Haemost 2008; 6 (10) 1615-1621
    CrossrefPubMedGoogle Scholar
  • 21 Jamula E, Schwalm JD, Douketis JD. Periprocedural anticoagulation practices in warfarin-treated patients who require elective angiography with or without percutaneous coronary intervention: a retrospective chart review. Thromb Res 2010; 125 (04) 351-352
    CrossrefPubMedGoogle Scholar
  • 22 Madan S, Muthusamy P, Mowers KL. , et al. Safety of anticoagulation with uninterrupted warfarin vs. interrupted dabigatran in patients requiring an implantable cardiac device. Cardiovasc Diagn Ther 2016; 6 (01) 3-9
    PubMedGoogle Scholar
  • 23 Birnie DH, Healey JS, Wells GA. , et al; BRUISE CONTROL Investigators. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med 2013; 368 (22) 2084-2093
    CrossrefPubMedGoogle Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 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
    CrossrefPubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Kovacs RJ, Flaker GC, Saxonhouse SJ. , et al. Practical management of anticoagulation in patients with atrial fibrillation. J Am Coll Cardiol 2015; 65 (13) 1340-1360
    CrossrefPubMedGoogle Scholar
  • 28 Devereaux PJ, Mrkobrada M, Sessler DI. , et al; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370 (16) 1494-1503
    CrossrefPubMedGoogle Scholar
  • 29 Douketis JD, Healey JS, Brueckmann M. , et al. Urgent surgery or procedures in patients taking dabigatran or warfarin: analysis of perioperative outcomes from the RE-LY trial. Thromb Res 2016; 139: 77-81
    CrossrefPubMedGoogle Scholar
  • 30 Douketis JD, Spyropoulos AC, Anderson JM. , et al. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for patients on a direct oral anticoagulant who need an elective surgery or procedure: design and rationale. Thromb Haemost 2017; 117 (12) 2415-2424
    Article in Thieme ConnectPubMedGoogle Scholar