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Original Investigation
August 5, 2019

Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

Author Affiliations
  • 1Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  • 2The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Medicine, Northwell Health at Lenox Hill Hospital, New York, New York
  • 3Ottawa Hospital Research Institute, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  • 4L’Institut du Savoir Montfort, L’Hopital Montfort, Ottawa, Ontario, Canada
  • 5Department of Surgery, NorthShore University Health Systems, Evanston, Illinois
  • 6Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
  • 7Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
  • 8Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • 9Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 10Department of Medicine, Montreal General Hospital, McGill University, Montreal, Quebec, Canada
  • 11Department of Medicine, Université de Montréal, Montreal, Quebec, Canada
  • 12Department of Internal Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
  • 13Department of Anesthesiology, University of Manitoba, Winnipeg, Manitoba, Canada
  • 14Department of Medicine, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
  • 15Department of Medicine, Henry Ford Hospital, Detroit, Michigan
  • 16Department of Medicine, University of Calgary, Calgary, Alberta, Canada
  • 17Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
  • 18Department of Pharmacy, Kaiser Permanente Colorado, Aurora, Colorado
  • 19Department of Anesthesiology, University of Thessaly, Larissa, Greece
  • 20Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Location AMC, the Netherlands
  • 21Hamilton Regional Laboratory Medicine Program, McMaster University, Hamilton, Ontario, Canada
  • 22Department of Anesthesiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
  • 23Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia
JAMA Intern Med. Published online August 5, 2019. doi:10.1001/jamainternmed.2019.2431
Key Points

Question  Is a standardized perioperative management approach safe for patients with atrial fibrillation who use a direct oral anticoagulant and require elective surgery or procedure?

Findings  In this cohort study of 3007 patients with atrial fibrillation using apixaban, dabigatran, or rivaroxaban, the direct oral anticoagulant treatment was stopped and resumed before and/or after elective surgery or procedure using standardized protocols without heparin bridging. The 30-day postoperative rates of major bleeding were less than 2%, and the rates of stroke were less than 1%.

Meaning  In this study, in patients treated with a direct oral anticoagulant, a simple standardized perioperative management approach was associated with low rates of bleeding and stroke.


Importance  Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain.

Objective  To investigate the safety of a standardized perioperative DOAC management strategy.

Design, Setting, and Participants  The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol.

Interventions  A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low–bleeding-risk procedure and 2 days before a high–bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low–bleeding-risk procedure and 2 to 3 days after a high–bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation.

Main Outcomes and Measures  Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level (<50 ng/mL) at the time of the procedure.

Results  The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high–bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high–bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort.

Conclusions and Relevance  In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.

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