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. 2019 Nov 1;179(11):1469-1478.
doi: 10.1001/jamainternmed.2019.2431.

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

James D Douketis  1 , Alex C Spyropoulos  2 , Joanne Duncan  1 , Marc Carrier  3 , Gregoire Le Gal  4 , Alfonso J Tafur  5 , Thomas Vanassche  6 , Peter Verhamme  6 , Sudeep Shivakumar  7 , Peter L Gross  1 , Agnes Y Y Lee  8 , Erik Yeo  9 , Susan Solymoss  10 , Jeannine Kassis  11 , Geneviève Le Templier  12 , Stephen Kowalski  13 , Mark Blostein  14 , Vinay Shah  15 , Elizabeth MacKay  16 , Cynthia Wu  17 , Nathan P Clark  18 , Shannon M Bates  1 , Frederick A Spencer  1 , Eleni Arnaoutoglou  19 , Michiel Coppens  20 , Donald M Arnold  1 , Joseph A Caprini  5 , Na Li  1 , Karen A Moffat  21 , Summer Syed  22 , Sam Schulman  1   23
Affiliations

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

James D Douketis et al. JAMA Intern Med. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Douketis reported personal fees from Pfizer, Sanofi, Leo Pharma, Bristol-Myers Squibb, Janssen, The Merck Manual, and UpToDate outside of the submitted work. Dr Spyropoulos reported grants and personal fees from Janssen and Boehringer Ingelheim and personal fees from Bayer, Portola, and ATLAS Group outside of the submitted work. Dr Carrier reported grants from Canadian Institutes of Health Research (CIHR) during the conduct of the study; grants from Leo Pharma and BMS; grants and personal fees from Pfizer; and personal fees from Bayer, Seriver, BMS, and Leo Pharma outside of the submitted work. Dr Le Gal reported personal fees from Bayer, Pfizer, LEO Pharma, Sanofi, and bioMéerieux as well as other fees from Portola Pharmaceuticals, Boehringer-Ingelheim, Pfizer, Bristol-Myers Squibb, LEO Pharma, Daiichi Sankyo, and Bayer outside of the submitted work. Dr Tafur reported grants from PAUSE during the conduct of the study. Dr Vanassche reported other fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Leo pharma outside of the submitted work. Dr Verhamme reported grants and personal fees from Bayer HealthCare, Boehringer Ingelheim, Pfizer, BMS, Daiichi Sankyo, and Leo Pharma as well as personal fees from Portola outside of the submitted work. Dr Shivakumar reported personal fees from Pfizer Inc and Bayer Inc outside of the submitted work. Dr Gross reported other fees from Bayer and Pfizer; grants and other fees from Bristol-Myers-Squibb; and grants from Boehringer-Ingelheim during the conduct of the study; other fees from Servier, Leo Pharrma, and Alexion outside of the submitted work; and a patent to US10131932B2 method for assaying a protease issued. Dr Lee reported personal fees from Bayer, LEO Pharma, and Pfizer as well as grants, personal fees, and nonfinancial support from BMS during the conduct of the study. Dr Le Templier reported personal fees from BMS-Pfizer outside of the submitted work. Dr Shah reported grants from CIHR during the conduct of the study. Dr MacKay reported grants from CIHR during the conduct of the study and personal fees from BMS/Pfizer outside of the submitted work. Dr Wu reported other fees from Leo Pharma, Pfizer, Servier, BMS-Pfizer, Bayer, and Daiichi-Sankyo during the conduct of the study. Dr Bates reported grant 313156 from CIHR and grant G-14-0006136 from Heart and Stroke Foundation of Canada during the conduct of the study as well as grants from Bayer Inc outside of the submitted work. Dr Arnaoutoglou reported grants and personal fees from Bayer outside of the submitted work. Dr Coppens reported other fees from Bristol-Myers Squibb, Pfizer, and Boehringer-Ingelheim; grants, personal fees, and other fees from Bayer and Daiichi Sankyo; personal fees from Portola; and grants from Sanquin Blood Supply outside of the submitted work. Dr Caprini reported personal fees from BMS, Janssen, and Pfizer outside of the submitted work. Dr Syed reported personal fees and other fees from Octapharma outside of the submitted work. Dr Schulman reported grants and personal fees from Boehringer Ingelheim, Octapharma as well as personal fees from Bayer, Daiichi Sankyo, Pfizer, Alnylam, and Sanofi during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Perioperative Direct Oral Anticoagulant (DOAC) Management Protocol
No DOAC was taken on certain days (shaded) and on the day of the elective surgery or procedure. The light blue arrows refer to an exception to the basic management, a subgroup of patients taking dabigatran with a creatinine clearance (CrCl) less than 50 ng/mL. The orange arrows refer to patients having a high–bleed-risk surgical procedure. Dark blue arrows refer to patients having a low–bleed-risk surgical procedure. The thickened orange part of arrows refer to flexibility in the timing of DOAC resumption after a procedure. aCancer diagnosed within 3 months or has been treated within 6 months or metastatic.
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