By Cara N. Pellegrini, MD

Assistant Professor of Medicine, UCSF, Cardiology Division, Electrophysiology Section, San Francisco VA Medical Center

Dr. Pellegrini reports no financial relationships relevant to this field of study.

SOURCE: Steinberg BA, 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.

Despite the routine nature of discontinuing atrial fibrillation (AF) patients’ long-term oral anticoagulation (OAC) for procedures and “bridging” them with another agent, there is remarkably little data on the safety and benefit of this practice. Guidelines detailing when and how to initiate bridging therapy have been published, but data supporting why we should bridge at all are limited.1 To help fill this void, Steinberg and colleagues used a national, community-based registry of outpatients with AF (ORBIT-AF) to examine current practices around periprocedural OAC management and associated outcomes. Outcomes evaluated included rates of major bleeding, as well as myocardial infarction, stroke or systemic embolism, cause-specific hospitalization, and death within 30 days.

Their final study cohort consisted of 7372 patients, with a median follow-up of 24 months. They found a large proportion (30%) of patients had an interruption in their OAC during the study; of these, approximately one-quarter were bridged, most commonly with low-molecular weight heparin (73%), but a sizable minority with unfractionated heparin (15%). The decision to bridge a patient appeared to be driven primarily by the patient’s history of a prior cerebrovascular event (22% bridged vs 15% no bridging; P < 0.001), history of congestive heart failure (44% vs 34%; P < 0.001), and presence of a mechanical valve (9.6% vs 2.4%; P < 0.001). As expected, mean CHA2DS2-VASc scores were slightly higher in the bridged group as well (4.25 vs 4.03; P = 0.01). Interestingly, not only were bleeding events more common in the bridged group (5.0% vs 1.3%; adjusted odds ratio, 3.84; P < 0.001), but the incidence of the composite outcome of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days was also significantly higher in the bridged group (13% vs 6.3%; adjusted odds ratio, 1.94; P < 0.001). The authors concluded that their data do not support the use of routine bridging anticoagulation.

COMMENTARY

Clearly the biggest limitation of this trial was inherent in its design — this was not a randomized, controlled trial. The patient factors that led to their presumed designation as higher risk and, therefore, the decision to bridge them, also could have contributed to their worse outcomes. The authors attempted to correct for this by performing a multivariate-adjusted analysis to control for known biases, such as the higher CHA2DS2-VASc scores in the bridged group, but residual or unmeasured confounding cannot be excluded. Stay tuned for the results of the ongoing Effectiveness of Bridging Anticoagulation for Surgery (BRIDGE) study, which will be able to address the issue of causality, and which has now completed randomization of about 2000 patients undergoing surgery to low-molecular weight heparin bridging or placebo during the perioperative period.

Nonetheless, there are some important lessons for now. Bridging almost certainly comes at a cost, at a minimum, of an increased bleeding risk. This finding echoes that of a recent meta-analysis of > 12,000 patients from 34 studies (only one of which was a randomized controlled trial), which found bridging therapy to be associated with an increased risk of bleeding events, and a similar risk of thromboembolic events.2 Given the mounting evidence that bridging may be harmful, or at least not as helpful as we thought, unless patients are at particularly high risk for a thromboembolic event, it seems prudent to not bridge. Additionally, extra consideration of whether bridging is necessary should be given to patients undergoing certain procedures, such as endoscopy and catheter ablation, that appear to have excess risk (bleeding and cardiovascular events respectively) with a bridging approach.

Perhaps even better is to not interrupt OAC for procedures at all. While this was not a primary focus of this study, there is a growing body of literature supporting that approach for catheter ablation of AF and cardiac device implantation.3,4 Particularly low-risk procedures, such as dental work, minor skin procedures, or cataract surgery in which bleeding can be locally prevented (with a special mouthwash for example) or is expected to be minimal, do not generally warrant OAC interruption. Approximately 5% of the patients treated with dabigatran at baseline (the only novel agent included in this study) were bridged, a number appropriately less than the overall 25% bridging rate, but still probably higher than should be targeted when novel agents with a fast onset/offset are used. When bridging is performed, particular attention should be paid to periods of transition, such as hospital discharge, and needs for dosage adjustment to minimize the risks. While this study did not provide comparison data for low molecular weight heparin vs unfractionated heparin, other studies, such as BRUISE CONTROL, did not detect a significant difference between these bridging approaches.4

REFERENCES

  1. January CT, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology / American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation 2014;130:e199-267.
  2. Siegal D, et al. Periprocedural hearpin bridging in patients receiving vitamin K antagonists: Systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation 2012;126:1630-1639.
  3. Di Biase L, et al. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: Results for the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation 2014;129:2638-2644.
  4. Birnie DH, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med 2013;368:2084-2093.