'A Bridge Too Far': Analysis Points to Bleeding Risks From Anticoagulation Bridging in AF

December 16, 2014

DURHAM, NC — Patients with atrial fibrillation (AF) who are bridged with low-molecular-weight heparin (LMWH) or unfractionated heparin during procedures requiring an interruption of oral anticoagulation are at a higher risk of adverse events than patients who are not bridged, a new analysis shows[1].

At 30 days, patients treated with bridging therapy were nearly four times more likely to have a major bleed or to be hospitalized for bleeding. In addition, individuals who received short-term anticoagulant bridging had a significantly higher risk of stroke, MI, major bleeding, hospitalization, or death within 30 days of the procedure that required the interruption of chronic anticoagulation.

There is the error of commission, which is the potential of bleeding in the setting of bridging, and there is the error of omission, which is the potential for thromboembolic events in the absence of bridging.

"Patients who get oral anticoagulation almost invariably have it stopped at some point over the period of their treatment, whether it's because they're not tolerating it, they have a bleeding episode, or, as in our analysis, they're undergoing a procedure," lead investigator Dr Benjamin Steinberg (Duke Clinical Research Institute, Durham, NC) told heartwire . "The management in and around those stoppages, whether temporary or not, is a major unanswered question."

The researchers found the interruption of oral anticoagulation was common over a two-year follow-up period—with 30% of patients stopping warfarin or dabigatran (Pradaxa, Boehringer Ingelheim) because of procedures that ranged from cardiac surgery to dental work—and that approximately one in four patients received bridging with LMWH or unfractionated heparin.

The observational report, an analysis of the US-wide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), is published December 12, 2014 in Circulation.

One in Four Patients Bridged

In ORBIT-AF, which included 7372 patients treated with oral anticoagulation at baseline, 2803 had to briefly stop treatment for various procedures, including cardiac surgery, endoscopy, catheterization/PCI, noncardiac surgery, and dental work.

Of those who stopped oral anticoagulation, 24% were bridged with short-acting bridging anticoagulation. The majority of patients were bridged with LMWH. Regarding baseline oral anticoagulation, more than 93% were treated with warfarin and a small percentage treated with dabigatran.

Adverse events during the interruption of oral anticoagulation were significantly higher among patients treated with bridging anticoagulation when compared with those not bridged (5.3% vs 2.8%; P=0.01). This was driven by a significantly higher rate of bleeding among those receiving bridging therapy (3.7% vs 1.8%; P=0.02). Major bleeding, hospitalization for bleeding events, and hospitalization for cardiovascular events were also significantly higher in the 30 days following the procedure requiring stoppage of oral anticoagulation among those who received bridging therapy.

Overall, the 30-day adjusted bleeding and overall composite event rate, which includes events during the interruption of oral anticoagulation and in the 30 days following the procedure requiring the stoppage, were significantly higher among those treated with bridging therapy.

Unadjusted and Adjusted 30-Day Outcomes
Clinical event No bridging, unadjusted % (n=1724) Bridging, unadjusted % (n=503) P Adjusted odds ratio bridging vs no bridging (95% CI)
Cardiovascular events 2.5 4.6 0.02 1.62 (0.95–2.78)
Bleeding events 1.3 5.0 <0.0001 3.84 (2.07–7.14)
Overall composite* 6.3 13 <0.0001 1.94 (1.38–2.71)
*Composite end point includes stroke, MI, major bleeding, hospitalization, or death within 30 days of stopping oral anticoagulation

"Clinicians are really challenged in patients with atrial fibrillation or those at risk for stroke, many of whom are also at risk for bleeding, particularly in the setting of procedures. There are questions in terms of when to stop their anticoagulant, how long in advance to stop, whether to use a short-term anticoagulant in the periprocedural period, and when to restart their chronic anticoagulation, if at all."

Historically, stopping and then restarting warfarin was believed to carry prothrombotic risks, which is an argument that has been made in support of bridging with other anticoagulants such as LMWH, said Steinberg. That said, many of the ACS and PCI studies have shown just how difficult it is to transition patients between anticoagulants. "It can be a setup for dosing problems," said Steinberg.

Guidelines Structured by Procedure Type and Risk

The American College of Chest Physicians (ACCP) recommends stopping oral anticoagulation and using a short-acting anticoagulant like LMWH or unfractionated heparin for the periprocedural management of patients with atrial fibrillation at high risk for thromboembolic events (grade 2C). The ACCP guidelines on the use of bridging are structured by procedure type and patient risk levels.

In their analysis, Steinberg noted that some patients undergoing dental procedures had their oral coagulant stopped even though the guidelines suggest that no interruption might be necessary. The ORBIT-AF study was not powered to analyze bleeding and cardiovascular risks by procedure type, he noted. Some procedures, such as catheter ablations, are often performed in patients on full anticoagulation, and randomized data have shown that device-implant patients tend to fare better without bridging.

"The guidelines certainly indicate the type of procedure influences, first of all, whether anticoagulation should be interrupted at all," said Steinberg. "After that decision, it then becomes a question of bridging."

In an editorial[2], Drs Amir Shaikh and David McManus (University of Massachusetts Medical School, Worchester) say the current findings "fly somewhat in the face of conventional dogma and may begin a paradigm shift away from the routine use of a bridging strategy for AF patients undergoing procedures."

The analysis from ORBIT-AF suggests that physicians in their zeal to reduce the risk of thromboembolic complications during these procedures might be exposing patients at a greater risk of bleeding complications. Like Steinberg and colleagues, the editorialists say clinical studies are needed to resolve the question definitively.

Two ongoing studies—the aptly named Effectiveness of Bridging Anticoagulation for Surgery (BRIDGE) study and the Safety and Effectiveness Study of LMWH Bridging Therapy versus Placebo Bridging Therapy for Patients on Long-Term Warfarin and Require Temporary Interruption of Their Warfarin (PERIOP-2)—are currently under way and will help guide periprocedural decision making, they note.

In the absence of clear clinical evidence, Steinberg told heartwire , anticoagulation in the setting of clinical procedures and whether or not to bridge is a "double-edged sword."

"There is the error of commission, which is the potential of bleeding in the setting of bridging, and there is the error of omission, which is the potential for thromboembolic events in the absence of bridging," he said. "Clinicians, historically, tend to shy away from errors of omission."

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