Is it Needed When Warfarin Is Interrupted Around the Time of a Surgery or Procedure?
- The BRIDGE Study Investigators
+ Author Affiliations
- Correspondence to Dr James D. Douketis, St. Joseph's Healthcare Hamilton, Room F-544, 50 Charlton Ave E, Hamilton, Ontario, Canada, L8N 4A6. E-mail email@example.com
There are many patients who are receiving long-term treatment with the blood thinner warfarin, whether because of atrial fibrillation (the commonest reason for taking warfarin) or a mechanical heart valve. Such patients frequently require warfarin to be stopped because of an upcoming surgery/procedure. There is uncertainty whether such patients should receive bridging anticoagulation before and after the surgery/ procedure.
The objectives of this article are to (1) clarify what is meant by bridging anticoagulation and for whom it should be considered and (2) to inform readers about the BRIDGE study (Bridging Anticoagulation in Patients Who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery), which aims to determine whether bridging anticoagulation is needed during warfarin interruption.
What Is Bridging Anticoagulation?
Bridging anticoagulation refers to giving a short-acting blood thinner, usually low-molecular-weight heparin given by subcutaneous injection for 10 to 12 days around the time of the surgery/procedure, when warfarin is interrupted and its anticoagulant effect is outside a therapeutic range. Bridging anticoagulation aims to reduce patients' risk for developing blood clots, such as stroke, but may also increase patients' risk for developing potentially serious bleeding complications after surgery.
How Is Bridging Anticoagulation Given?
After warfarin is stopped, 5 to 6 days before surgery (to allow sufficient time for its anticoagulant effect to wane), bridging anticoagulation is started 3 days before surgery, with the last dose given 24 hours before surgery. After surgery, bridging is resumed no earlier than 24 hours after surgery; at the same time, warfarin is restarted. Bridging is continued, typically for 4 to 6 days, until the anticoagulant effect of warfarin has resumed and the blood is sufficiently thinned again.
What Low-Molecular-Weight Heparin and What Dose Should Be Used for Bridging?
There is no standardized bridging drug or dose. A therapeutic-dose regimen, for example, enoxaparin (Lovenox) 1 mg/kg twice daily, is often used in North America, although some physicians in other countries use lower doses.
What Happens for Patients Who Are Having a Minor Procedure, Such as a Tooth Extraction or Skin Cancer Removal?
For patients having minor dental work, such as a tooth extraction or root canal, it may not be necessary to stop warfarin. Some dentists allow patients to continue warfarin (especially if there are concerns about stopping it), so long as they take a special mouthwash called tranexamic acid (Amicar) just before and 3 times daily for 1 to 2 days after the dental procedure, to help prevent bleeding. For patients having minor skin procedures or cataract surgery, interruption of warfarin is often not required because there is minimal bleeding.
What Happens for Patients Who Are Having a More Extensive Surgery/Procedure in Which the Bleeding Risk Is High?
In such patients (eg, those having hip or knee replacement or cancer surgery), bridging anticoagulation should be given carefully, especially after surgery. Some physicians may choose to delay the resumption of therapeutic-dose low-molecular-weight heparin bridging for 2 to 3 days after surgery, and others may substitute a lower dose of low-molecular-weight heparin after surgery. There is no single approach, but the intent is to prevent bleeding, typically at the surgical/procedure site. If bleeding occurs, it will further delay the resumption of anticoagulation and will expose patients to an increased risk for blood clots. In other words, if bleeding occurs (perhaps because low-molecular-weight heparin bridging was given too close to surgery), this will have the opposite effect of what bridging was meant to do and can harm patients.
Who Should Receive Bridging Anticoagulation?
This is an unanswered question, because there are no completed high-quality clinical studies (referred to as randomized, controlled trials) that tell us who should be bridged. In the meantime, clinical experts have suggested a risk classification scheme to help identify which patients may or may not need bridging (Table), but much work needs to be done. The BRIDGE study will help to address this large gap in our knowledge.
View this table:
What Is the BRIDGE Study?
The BRIDGE study is a National Institutes of Health–sponsored randomized trial (registered at http://www.clinicaltrials.gov/, unique identifier NCT00786474) that aims to determine whether bridging anticoagulation is needed in patients with atrial fibrillation who are receiving warfarin and need to undergo a surgery/procedure. Eligible patients are randomly allocated to receive bridging anticoagulation (dalteparin 100 IU/kg twice daily) or matching placebo when warfarin is interrupted. BRIDGE will study >3600 patients in >90 clinical centers in the United States, Canada, and Brazil. A more detailed description of the study is available at the BRIDGE public Web site (https://bridge.dcri.duke.edu/).
Why Is the BRIDGE Study Needed?
In simple terms, we do not know whether bridging anticoagulation helps patients. On the one hand, some physicians think it may reduce patients' risk for developing stroke and other blood clots. On the other hand, others think it is not helpful and may cause harm by increasing the risk for bleeding complications. When such uncertainty exists about whether a treatment works, a randomized trial is justified to determine best practices and is ethical. Studies such as BRIDGE are also important because of the many patients (millions worldwide) for whom the results are applicable.
Who Is Eligible to Participate in the BRIDGE Study?
Warfarin-treated patients with atrial fibrillation or flutter (nonvalvular or valvular) with ≥1 additional risk factor for stroke (age ≥75 years, hypertension, diabetes mellitus, congestive heart failure, prior stroke or transient ischemic attack) and who require an elective (nonemergency) surgery/procedure are eligible.
Will a Placebo-Controlled Trial (or Bridging or No Bridging) Be Acceptable to Patients and Their Physicians?
Any placebo-controlled trial should be considered carefully. The BRIDGE investigators believe such a trial is acceptable for 3 reasons: (1) The efficacy and safety of bridging anticoagulation are not established; we simply do not know whether bridging works. (2) There is no established standard of care. This means that among patients who require warfarin interruption, a no-bridging approach is as acceptable as bridging. (3) Clinical practice guidelines provide weak (or uncertain) recommendations about whether to bridge, because sufficient evidence from well-designed trials is lacking.
How Can I (as a Patient or a Physician) Help the BRIDGE Study to Answer the Question of Whether “Bridging Anticoagulation” Is Needed?
Sources of Funding
This work did not receive any funding support. The BRIDGE Trial is funded by the National Institutes of Health's National Heart, Lung, and Blood Institute.
- © 2012 American Heart Association, Inc.