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Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation
Open accessAbstract
BACKGROUND: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS: In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). CONCLUSIONS: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).
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“In a randomized trial of 1884 patients with AF, interruption of anticoagulation was non-inferior to heparin administration for the outcome of arterial thromboembolism (incidence of 0.4% and 0.3%, respectively) and resulted in a lower risk of major bleeding (1.3% and 3.2%, respectively).502”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [502]
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“publication of the BRIDGE trial results [15].”
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Lee, J. H., Lim, H. E., Lim, W., Ahn, J., Cha, M., Park, J., Lee, K. H., Park, H.-C., Choi, E., & Joung, B. (2019) · Korean Journal of Medicine · doi:10.3904/kjm.2019.94.1.40 · Cited by 7
“교 요법을 하는 것은 출혈의 위험을 높이는 반면 여러 심혈 관계 사건을 줄이지 못했다[17].”
Update in perioperative medicine: practice changing evidence published in 2016
Regan, D. W., Kashiwagi, D. T., Dougan, B. M., Sundsted, K. K., & Mauck, K. F. (2017) · Hospital Practice · doi:10.1080/21548331.2017.1359060 · Cited by 7
“In 2015, the BRIDGE trial was the first randomized controlled trial (RCT) comparing BAC to no BAC in patientswith AF [14].”
BackgroundSpyropoulos, A. C., Giannis, D., Cohen, J. L., John, S., Myrka, A., Inlall, D., Qiu, M., Akgul, S., Hyman, R. J., & WANG, J. J. (2020) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/1076029620925910 · Cited by 7
Analysis of the ESC/EACTS 2020 Atrial Fibrillation Guidelines With Perioperative Implications
Nelson, J. A., Gue, Y. X., Christensen, J. M., Lip, G. Y. H., & Ramakrishna, H. (2021) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2021.05.011 · Cited by 8
Hakoda, A., Takeuchi, T., Kojima, Y., Fujiwara, Y., Nagami, Y., Naito, Y., Fukuda, S., Koike, T., Sugimoto, M., Hamada, K., et al. (2021) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.21-136 · Cited by 7
Banaszkiewicz, M., Kurzyna, P., Kubikowska, N., Mucha, M., Rudnik, A., Gąsecka, A., Pietrasik, A., Grabowski, M., Jaguszewski, M. J., Kasprzyk, P., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12165336 · Cited by 7
“However, it is worth noting that bridging therapy is regarded to be linked with a higher risk of bleeding [31].”
BackgroundLenga, P., Trong, P. D., Papakonstantinou, V., Unterberg, A. W., Krieg, S. M., & Ishak, B. (2024) · Brain and Spine · doi:10.1016/j.bas.2024.102768 · Cited by 7
“Recent literature indicates an elevated bleeding risk without a corresponding rise in thromboembolic events, regardless of antidote use or bridging therapy (Douketis et al., 2015; Siegal et al., 2012).”
BackgroundA rare case of Wunderlich syndrome five days after left hemicolectomy for colorectal cancer
Grassia, M., Romano, A., Esposito, G., Braccio, B., Pezzella, M., Rossetti, A. R. R., Torelli, F., Izzo, G., Alfano, R., & Martino, N. D. (2015) · International Journal of Surgery Case Reports · doi:10.1016/j.ijscr.2015.09.007 · Cited by 7
Qureshi, A. I., Jahangir, N., Malik, A., Afzal, M. R., Orfi, F., & Suri, M. F. K. (2016) · Cerebrovascular Diseases · doi:10.1159/000446406 · Cited by 7
Novel (Oral) Anticoagulant Challenges in Surgery
Blennerhassett, R. C., Favaloro, E. J., & Pasalic, L. (2017) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0037-1602667 · Cited by 7
Pulmonary embolism four days after interruption of therapy with rivaroxaban
Göndör, G., & Stöllberger, C. (2017) · Hämostaseologie · doi:10.5482/hamo-17-01-0005 · Cited by 7
Fabbro, M., Dunn, S. A., Rodriguez‐Blanco, Y. F., & Jain, P. (2018) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2018.07.023 · Cited by 7
Steuerung der NOAK-Gabe bei invasiven oder operativen Interventionen
Buerke, M., & Hoffmeister, H.-M. (2017) · Medizinische Klinik - Intensivmedizin und Notfallmedizin · doi:10.1007/s00063-016-0240-2 · Cited by 7
Perioperative Management of Direct Oral Anticoagulants in Intracranial Surgery
Porter, J. L., & Dinsmore, J. (2019) · Journal of Neurosurgical Anesthesiology · doi:10.1097/ana.0000000000000629 · Cited by 7
Management of anticoagulation and antiplatelet agents in the radical cystectomy patient
Smelser, W., & Jones, C. P. (2020) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2019.12.011 · Cited by 7
Hamada, K., Kanzaki, H., Inoue, M., Ishiyama, S., Yamauchi, K., Miyahara, K., Toyokawa, T., Tsuzuki, T., Miyaike, J., Matsubara, M., et al. (2020) · Internal Medicine · doi:10.2169/internalmedicine.4998-20 · Cited by 7
Elshaer, A., & Abraham, N. S. (2023) · Gastrointestinal Endoscopy Clinics of North America · doi:10.1016/j.giec.2023.09.002 · Cited by 8
Jalaber, E., Orvain, C., Papadopoulou, V., Genthon, A., Daguerre, V., Barrière, S., Teste, A., Tavernier, E., Daguenet, É., & Chalayer, É. (2025) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-025-03085-3 · Cited by 6
“In other clinical situations in AF, e.g. perioperatively, pursuit of anticoagulation has already been questioned and interruption without bridging is suggested according to some criteria [32].”
Interdisziplinäre Aspekte der oralen Antikoagulation mit NOAKs bei Vorhofflimmern
Dürschmied, D., Goette, A., Hardt, R., Kleinschnitz, C., Kämmerer, W., Lembens, C., Schmitt, W. H., & Bode, C. (2021) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-1472-3188 · Cited by 6
Living on Oral Anticoagulants: Duke Anticoagulation Satisfaction Scale Results
Mameli, A., Sestu, A., Marongiu, F., & Barcellona, D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12247574 · Cited by 7
“It is curious to note that this concern of bleeding is in line with the results of the BRIDGE study that showed that a higher incidence of major bleeding events was recorded in patients treated with the bridging therapy when compared to those who did not [22].”
ResultHrubesz, G., Dwyer, K., McIsaac, D. I., Sood, M. M., Clark, E. G., Douketis, J. D., Carrier, M., & Shaw, J. R. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023012380 · Cited by 6
Kulikov, A. S., Gruenbaum, S. E., Quiñones‐Hinojosa, A., Pugnaloni, P. P., Lubnin, A. Y., & Bilotta, F. (2024) · World Neurosurgery · doi:10.1016/j.wneu.2024.03.018 · Cited by 6
Sylvester, K. W., Grandoni, J., Rhoten, M. N., Coakley, L., Matiello, E., Frankel, K. A., Fortin, B. M., JOLLEY, K., Park, H. S., Freedman, R., et al. (2024) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2024.02.022 · Cited by 6
Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation
Chinese Society of Cardiology, C. M. A., & Heart Rhythm Committee of Chinese Society of Biomedical Engineering (2024) · Cardiology Discovery · doi:10.1097/cd9.0000000000000123 · Cited by 7
Schumacher, B., Reichle, B., Sommer, P., Davé, T., Levenson, B., Reinecke, H., Stellbrink, C., Steinbeck, G., & Mengel, R. (2017) · Der Kardiologe · doi:10.1007/s12181-017-0152-2 · Cited by 6
Safety of percutaneous nephrolithotomy in patients on chronic anticoagulant or antiplatelet therapy
Baltar, C. F., Pérez-Fentes, D., Sánchez-Garcia, J. F., & García-Freire, C. (2018) · Urolithiasis · doi:10.1007/s00240-018-1034-1 · Cited by 6
Warden, B. A., Diep, C., Ran, R., Thomas, M. B., & Cigarroa, J. E. (2019) · Clinical Cardiology · doi:10.1002/clc.23256 · Cited by 6
Rebello, D. (2019) · Annals of Gastroenterology · doi:10.20524/aog.2019.0430 · Cited by 6
“In one randomized controlled trial comparing bridge therapy to a no-bridge strategy in patients undergoing a variety of elective surgical and other invasive procedures, the use of hep-bridge resulted in more major bleeding, without a significant benefit in terms of preventing arterial thrombosis [32].”
Background
Metadata
- Authors
- Douketis, J. D., Spyropoulos, A. C., Kaatz, S., Becker, R. C., Caprini, J. A., Dunn, A. S., Garcia, D. A., Jacobson, A., Jaffer, A. K., Kong, D. F., Schulman, S., Turpie, A. G. G., Hasselblad, V., & Ortel, T. L.
- Affiliations
- Rush University Medical Center (US)
- Northwell Health (US)
- Hurley Medical Center (US)
- University of Cincinnati (US)
- Endeavor Health (US)
- University of Washington Medical Center (US)
- Duke Medical Center (US)
- McMaster University (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-08-27
- Volume
- 373
- Issue
- 9
- Pages
- 823-833
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4931686
- OpenAlex
- W1837600385
- Cited by
- 1,184
- References
- 46
- Citations by year
- 2026: 63 · 2025: 64 · 2024: 79 · 2023: 70 · 2022: 87 · 2021: 115 · 2020: 132 · 2019: 117 · 2018: 134 · 2017: 141 · 2016: 141 · 2015: 35
- FWCI
- 109.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (U01HL086755, U01HL087229)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- atrial fibrillation, low molecular weight heparin, dalteparin, warfarin interruption, arterial thromboembolism, major bleeding, elective surgery, non-inferiority, stroke prevention, systemic embolism, transient ischemic attack, postoperative bleeding risk
- MeSH terms
- Adult, Anticoagulants, Atrial Fibrillation, Double-Blind Method, Female, Hemorrhage, Heparin, Low-Molecular-Weight, Humans, Male, Postoperative Complications, Thromboembolism, Warfarin, Elective Surgical Procedures, Perioperative Period
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