Anticoagulation bridging: Is the juice worth the bleeds?
More than 35 million prescriptions for an oral anticoagulant are filled each year in the US. That is one prescription for every 100 adults. And a large number of these prescriptions are for patients with atrial fibrillation to prevent stroke. [For the sake of this show this week, we’re going to focus only on patients with atrial fibrillation. Anticoagulation for valvular disease and venous thromboembolism has some subtle differences.] Not surprisingly, patients on blood thinners can have other problems, and many are just as likely to require surgery as those who are not taking an anticoagulant. In fact, 1 in 6 patients taking a blood thinner will undergo an invasive procedure or surgery every year, putting them at risk of major bleeding, thromboembolism, and even death. So, how do you strike that balance between the need for anticoagulation and the need for hemostasis in the operating room? This week, I’m joined by Dr. Mike Rubenstein, who has seen standard practices change over the last 30 years, and shares his experience with anticoagulation bridging.
Some of the earliest arguments for bridging anticoagulation in the perioperative setting originated because of medications like warfarin, which has a half life of about 40 hours. So, if you were taking this medication, and you needed to undergo a procedure with some bleeding risk (even a colonoscopy), you would often be asked to stop taking it for several days, or even a week. And then post-operatively as you resume the warfarin, it would take another few days or a week for you to become therapeutically anticoagulated. Presumably, while off this treatment, you are at risk of cardiac thromboembolism from Afib. So doctors asked, is there a better way to prevent thromboembolism while you are not anticoagulated on warfarin?
Yes. Physicians could prescribe a short course of a medication with a far shorter half-life, like unfractionated or low molecular weight heparin, to maintain therapeutic anticoagulation, while you were not taking warfarin. The next
question became, is this safe? The risks and benefits must be weighed. So let’s imagine equally serious, and life-altering complications of either bridging or not bridging. If you are bridged, you could have minor bleeding, reactions to the new blood thinner, thrombocytopenia–issues which are either very minor or very rare. More concerning is if the bridging causes major bleeding (e.g., bleeding that If you are not bridged, you could develop an atrial thrombus, you could have renal, splenic, or mesenteric infarcts–all rare, but possible. Yet, not very concerning because they often never lead to serious morbidity. Cerebral embolism, however, is HUGELY concerning, and is probably as concerning as major bleeding. So let’s choose this as our adverse outcome if you avoid bridging. Among these two outcomes, major bleeding or cerebral embolism, which is more likely to occur over a 1 week span?
Well, what is the likelihood of stroke in patients with Afib to begin with? Years ago, the Stroke Prevention in Atrial Fibrillation Study reported that the annual risk of ischemic stroke was 5-7% in patients not on an antithrombotic agent. Which is pretty high, a more than 1 in 20 chance you will have a stroke every year with afib. And this risk falls by 67% with warfarin use. But again, that’s over a 1-year period. What about over a 1-week period? A later observational study of over 1,000 patients conducted by Garcia and colleagues reported that the risk of thromboembolism was very low in patients who had to be discontinued from their antithrombotic therapy. Over 30 days, the rate of systemic embolism was 0.6%, and the rate of ischemic stroke was 0.4%. Extrapolating the data from SPAF, this 0.4% may drop by 67%, to 0.13%. (Other experts estimate the risk is closer to 0.04% over a 4-day perioperative period, which falls to 0.01% with bridging.)
Now what is the likelihood of major bleeding in surgery? Pooled data indicate that the risk of any significant bleeding at the time of an invasive procedure is about 2.8%. 1 in 36 surgerized patients. Regardless of bridging. If your patient is bridged, the risk shoots up from 2.8% to nearly 12%. A 1 in 8 chance. For any bleeding. The risk of major bleeding, our primary outcome of interest which results in transfusions, transfusion-related complications, and increases hospital stay and risk of death (10% risk!), this risk is lower than the 1 in 8 chance with any bleeding. But still high. The risk of major bleeding with bridging is reported to be 3.5% vs. ~1% in surgerized patients who aren’t bridged.
3.5% risk of major bleeding over 1 week vs. 0.04-0.13% risk of ischemic stroke with anticoagulation bridging.
The 2015 BRIDGE trial remains the only randomized trial that has evaluated the safety and efficacy of anticoagulant bridging. The BRIDGE trial was a randomized, double-blind, placebo-controlled trial in which low-risk patients taking warfarin were “bridged” w/ LMWH for 3 days pre-op (held 24h pre-op), and continued on LMWH for 5-10 days post-op before resuming the VKA. High-risk patients were specifically excluded (nobody was included if they had a prior stroke in last 12 weeks, no mechanical valves, no bleeding complications). What they observed in 1800 patients was that bridging was non-inferior to interrupted anticoagulation for preventing thromboembolism. Stroke rates were the same regardless of heparinization. In fact, the incidence of major bleeding nearly tripled (3.2% vs. 1.3%) in the group who was bridged vs. those who stopped oral AC entirely, and this was statistically significant. So risks of bleeding are certainly greater in these patients at lower risk of thromboembolism. The PERIOP2 trial is ongoing and will specifically be targeting patients like this who may benefit from bridging therapy with dabigatran. But until these results are published, we’re relying on expert opinions and observational studies to determine if high risk patients ought to be heparinized around the time of an invasive procedure.
What do the experts recommend? CHEST guidelines are updated every few years, and the 2012 statement has summarized appropriate indications for anticoagulation bridging. To crudely summarize it, providers are encouraged to discontinue vitamin K antagonists 5 days before any surgery with bleeding risk. Providers should not bridge unless there are extenuating circumstances. In their words: In patients with a mechanical heart valve, atrial fibrillation, or VTE at moderate risk for thromboembolism, the bridging or no-bridging approach chosen is, as in the higher- and lower-risk patients, based on an assessment of individual patient- and surgery-related factors. The American Heart Association released an updated statement in 2017 outlining a risk stratification schema in detail for the novel oral anticoagulants, which is similar, and also vague. Ultimately, it is up to the provider to be aware of these data, and to recognize that the risk of systemic thromboembolism is very rare. And the risk of bleeding is dependent on the surgery and the patient’s status.
BrainWaves’ podcasts and online content are intended for medical education purposes only and should not be used for routine clinical care of patients. If you’re choosing between interrupting or bridging a patient’s anticoagulation for an upcoming procedure, you should read the literature yourself. I don’t think it will hold up in court if you have to say, “A podcast told me to give the patient heparin before her brain surgery.”
- Rechenmacher SJ, Fang JC. Bridging anticoagulation: Primum non nocere. Journal of the American College of Cardiology. 2015;66:1392-1403
- Steinberg BA, Peterson ED, Kim S, Thomas L, Gersh BJ, Fonarow GC, et al. Use and outcomes associated with bridging during anticoagulation interruptions in patients with atrial fibrillation: Findings from the outcomes registry for better informed treatment of atrial fibrillation (orbit-af). Circulation. 2015;131:488-494
- Stroke prevention in atrial fibrillation study. Final results. Circulation. 1991;84:527-539
- Garcia DA, Regan S, Henault LE, Upadhyay A, Baker J, Othman M, et al. Risk of thromboembolism with short-term interruption of warfarin therapy. Archives of internal medicine. 2008;168:63-69
- Raval AN, Cigarroa JE, Chung MK, Diaz-Sandoval LJ, Diercks D, Piccini JP, et al. Management of patients on non-vitamin k antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the american heart association. Circulation. 2017;135:e604-e633
- Schulman S, Carrier M, Lee AY, Shivakumar S, Blostein M, Spencer FA, et al. Perioperative management of dabigatran: A prospective cohort study. Circulation. 2015;132:167-173