James D Douketis1, Alex C Spyropoulos2, Joanne Duncan1, Marc Carrier3, Gregoire Le Gal4, Alfonso J Tafur5, Thomas Vanassche6, Peter Verhamme6, Sudeep Shivakumar7, Peter L Gross1, Agnes Y Y Lee8, Erik Yeo9, Susan Solymoss10, Jeannine Kassis11, Geneviève Le Templier12, Stephen Kowalski13, Mark Blostein14, Vinay Shah15, Elizabeth MacKay16, Cynthia Wu17, Nathan P Clark18, Shannon M Bates1, Frederick A Spencer1, Eleni Arnaoutoglou19, Michiel Coppens20, Donald M Arnold1, Joseph A Caprini5, Na Li1, Karen A Moffat21, Summer Syed22, Sam Schulman1,23. 1. Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 2. The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Medicine, Northwell Health at Lenox Hill Hospital, New York, New York. 3. Ottawa Hospital Research Institute, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. 4. L'Institut du Savoir Montfort, L'Hopital Montfort, Ottawa, Ontario, Canada. 5. Department of Surgery, NorthShore University Health Systems, Evanston, Illinois. 6. Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. 7. Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. 8. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 9. Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 10. Department of Medicine, Montreal General Hospital, McGill University, Montreal, Quebec, Canada. 11. Department of Medicine, Université de Montréal, Montreal, Quebec, Canada. 12. Department of Internal Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada. 13. Department of Anesthesiology, University of Manitoba, Winnipeg, Manitoba, Canada. 14. Department of Medicine, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 15. Department of Medicine, Henry Ford Hospital, Detroit, Michigan. 16. Department of Medicine, University of Calgary, Calgary, Alberta, Canada. 17. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. 18. Department of Pharmacy, Kaiser Permanente Colorado, Aurora, Colorado. 19. Department of Anesthesiology, University of Thessaly, Larissa, Greece. 20. Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Location AMC, the Netherlands. 21. Hamilton Regional Laboratory Medicine Program, McMaster University, Hamilton, Ontario, Canada. 22. Department of Anesthesiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada. 23. Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia.
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.
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.
Authors: Muhammad Umer Siddiqui; Ahmed K Pasha; Ibtisam Rauf; Justin Z Lee; Muhammad Danial Siddiqui; Youssef Yaacoub; Mohammad Reza Movahed Journal: Clin Med Res Date: 2020-10-14
Authors: Geoffrey D Barnes; Yun Li; Xiaokui Gu; Brian Haymart; Eva Kline-Rogers; Mona A Ali; Jay Kozlowski; Gregory Krol; James B Froehlich; Scott Kaatz Journal: J Thromb Haemost Date: 2020-06-25 Impact factor: 5.824
Authors: Neena S Abraham; Alan N Barkun; Bryan G Sauer; James Douketis; Loren Laine; Peter A Noseworthy; Jennifer J Telford; Grigorios I Leontiadis Journal: J Can Assoc Gastroenterol Date: 2022-03-17
Authors: Joseph R Shaw; Na Li; Thomas Vanassche; Michiel Coppens; Alex C Spyropoulos; Summer Syed; Mansoor Radwi; Joanne Duncan; Sam Schulman; James D Douketis Journal: Blood Adv Date: 2020-08-11