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

James D. Douketis; Alex C. Spyropoulos; Joanne Duncan; Marc Carrier; Gregoire Le Gal; Alfonso J. Tafur; Thomas Vanassche; Peter Verhamme; Sudeep Shivakumar; Peter L. Gross; Agnes Y.Y. Lee; Erik Yeo; Susan Solymoss; Jeannine Kassis; Geneviève Le Templier; Stephen Kowalski; Mark Blostein; Vinay Shah; Elizabeth Mackay; Cynthia Wu; Nathan P. Clark; Shannon M. Bates; Frederick A. Spencer; Eleni Arnaoutoglou; Michiel Coppens; Donald M. Arnold; Joseph A. Caprini; Na Li; Karen A. Moffat; Summer Syed; Sam Schulman

doi:10.1001/jamainternmed.2019.2431

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

James D. Douketis, Alex C. Spyropoulos, Joanne Duncan, Marc Carrier, Gregoire Le Gal, Alfonso J. Tafur, Thomas Vanassche, Peter Verhamme, Sudeep Shivakumar, Peter L. Gross, Agnes Y.Y. Lee, Erik Yeo, Susan Solymoss, Jeannine Kassis, Geneviève Le Templier, Stephen Kowalski, Mark Blostein, Vinay Shah, Elizabeth Mackay, Cynthia WuNathan P. Clark, Shannon M. Bates, Frederick A. Spencer, Eleni Arnaoutoglou, Michiel Coppens, Donald M. Arnold, Joseph A. Caprini, Na Li, Karen A. Moffat, Summer Syed, Sam Schulman

Medicine

Research output: Contribution to journal › Article › peer-review

363 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1469-1478
Number of pages	10
Journal	JAMA Internal Medicine
Volume	179
Issue number	11
DOIs	https://doi.org/10.1001/jamainternmed.2019.2431
Publication status	Published - Nov 2019

Bibliographical note

Funding Information:
Funding/Support: The PAUSE study was funded by grant 313156 from the Canadian Institutes of Health Research and grant G-14-0006136 from the Heart and Stroke Foundation of Canada. Additional support was provided by the CanVECTOR research network. In-kind support was obtained from Aniara-Hyphen Biomed, which provided the anti–factor Xa and dilute thrombin time assays.

Funding Information:
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.

Publisher Copyright:
© 2019 American Medical Association. All rights reserved.

ASJC Scopus Subject Areas

Internal Medicine

Access to Document

10.1001/jamainternmed.2019.2431

Cite this

Douketis, J. D., Spyropoulos, A. C., Duncan, J., Carrier, M., Le Gal, G., Tafur, A. J., Vanassche, T., Verhamme, P., Shivakumar, S., Gross, P. L., Lee, A. Y. Y., Yeo, E., Solymoss, S., Kassis, J., Le Templier, G., Kowalski, S., Blostein, M., Shah, V., Mackay, E., ... Schulman, S. (2019). Perioperative Management of Patients with Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Internal Medicine, 179(11), 1469-1478. https://doi.org/10.1001/jamainternmed.2019.2431

Douketis, JD, Spyropoulos, AC, Duncan, J, Carrier, M, Le Gal, G, Tafur, AJ, Vanassche, T, Verhamme, P, Shivakumar, S, Gross, PL, Lee, AYY, Yeo, E, Solymoss, S, Kassis, J, Le Templier, G, Kowalski, S, Blostein, M, Shah, V, Mackay, E, Wu, C, Clark, NP, Bates, SM, Spencer, FA, Arnaoutoglou, E, Coppens, M, Arnold, DM, Caprini, JA, Li, N, Moffat, KA, Syed, S & Schulman, S 2019, 'Perioperative Management of Patients with Atrial Fibrillation Receiving a Direct Oral Anticoagulant', JAMA Internal Medicine, vol. 179, no. 11, pp. 1469-1478. https://doi.org/10.1001/jamainternmed.2019.2431

@article{03480ccfe41e4531b037dbae4bd9c855,

title = "Perioperative Management of Patients with Atrial Fibrillation Receiving a Direct Oral Anticoagulant",

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.",

author = "Douketis, {James D.} and Spyropoulos, {Alex C.} and Joanne Duncan and Marc Carrier and {Le Gal}, Gregoire and Tafur, {Alfonso J.} and Thomas Vanassche and Peter Verhamme and Sudeep Shivakumar and Gross, {Peter L.} and Lee, {Agnes Y.Y.} and Erik Yeo and Susan Solymoss and Jeannine Kassis and {Le Templier}, Genevi{\`e}ve and Stephen Kowalski and Mark Blostein and Vinay Shah and Elizabeth Mackay and Cynthia Wu and Clark, {Nathan P.} and Bates, {Shannon M.} and Spencer, {Frederick A.} and Eleni Arnaoutoglou and Michiel Coppens and Arnold, {Donald M.} and Caprini, {Joseph A.} and Na Li and Moffat, {Karen A.} and Summer Syed and Sam Schulman",

note = "Funding Information: Funding/Support: The PAUSE study was funded by grant 313156 from the Canadian Institutes of Health Research and grant G-14-0006136 from the Heart and Stroke Foundation of Canada. Additional support was provided by the CanVECTOR research network. In-kind support was obtained from Aniara-Hyphen Biomed, which provided the anti–factor Xa and dilute thrombin time assays. Funding Information: 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 bioM{\'e}erieux 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. Publisher Copyright: {\textcopyright} 2019 American Medical Association. All rights reserved.",

year = "2019",

month = nov,

doi = "10.1001/jamainternmed.2019.2431",

language = "English",

volume = "179",

pages = "1469--1478",

journal = "JAMA Internal Medicine",

issn = "2168-6106",

publisher = "American Medical Association",

number = "11",

}

TY - JOUR

T1 - Perioperative Management of Patients with Atrial Fibrillation Receiving a Direct Oral Anticoagulant

AU - Douketis, James D.

AU - Spyropoulos, Alex C.

AU - Duncan, Joanne

AU - Carrier, Marc

AU - Le Gal, Gregoire

AU - Tafur, Alfonso J.

AU - Vanassche, Thomas

AU - Verhamme, Peter

AU - Shivakumar, Sudeep

AU - Gross, Peter L.

AU - Lee, Agnes Y.Y.

AU - Yeo, Erik

AU - Solymoss, Susan

AU - Kassis, Jeannine

AU - Le Templier, Geneviève

AU - Kowalski, Stephen

AU - Blostein, Mark

AU - Shah, Vinay

AU - Mackay, Elizabeth

AU - Wu, Cynthia

AU - Clark, Nathan P.

AU - Bates, Shannon M.

AU - Spencer, Frederick A.

AU - Arnaoutoglou, Eleni

AU - Coppens, Michiel

AU - Arnold, Donald M.

AU - Caprini, Joseph A.

AU - Li, Na

AU - Moffat, Karen A.

AU - Syed, Summer

AU - Schulman, Sam

N1 - Funding Information: Funding/Support: The PAUSE study was funded by grant 313156 from the Canadian Institutes of Health Research and grant G-14-0006136 from the Heart and Stroke Foundation of Canada. Additional support was provided by the CanVECTOR research network. In-kind support was obtained from Aniara-Hyphen Biomed, which provided the anti–factor Xa and dilute thrombin time assays. Funding Information: 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. Publisher Copyright: © 2019 American Medical Association. All rights reserved.

PY - 2019/11

Y1 - 2019/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071247441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071247441&partnerID=8YFLogxK

U2 - 10.1001/jamainternmed.2019.2431

DO - 10.1001/jamainternmed.2019.2431

M3 - Article

C2 - 31380891

AN - SCOPUS:85071247441

SN - 2168-6106

VL - 179

SP - 1469

EP - 1478

JO - JAMA Internal Medicine

JF - JAMA Internal Medicine

IS - 11

ER -

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Access to Document

Other files and links

Fingerprint

Cite this