By Michael H. Crawford, MD

Professor of Medicine, Lucie Stern Chair in Cardiology, Director, Cardiology Fellowship Program, Chief of Clinical Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study. This article originally appeared in the October 2014 issue of Clinical Cardiology Alert.

SOURCE: Beyer-Westendorf J, et al. Peri-interventional management of novel oral anticoagulants in daily care: Results from the prospective Dresden NOAC registry. Eur Heart J 2014;35:1888-1896.

Due to the short half-life and rapid onset of action of the new oral anticoagulants (NOACs), peri-procedural anticoagulant free time intervals should be shorter than with warfarin. Thus, there is uncertainty about the use of heparin bridging. These investigators from Germany analyzed the Dresden NOAC registry data to assess peri-procedural NOAC management and safety until 30 days post-procedure. The primary effectiveness outcome was a combination of centrally adjudicated cardiovascular events, including death. The primary safety outcome was the rate of major bleeding events. Among the 2179 patients, 27% underwent procedures (16% minimal, 74% minor, and 10% major). Most of the patients were on rivaroxaban (76%) for stroke prevention in atrial fibrillation (81%). Peri-procedure, 1% of these patients had a major cardiovascular event and 1.2% had major bleeding. The rates of these complications were highest for major procedures (5% and 8%, respectively). During the 863 procedures, NOACs were continued in 22%, temporarily stopped in 49%, or stopped with heparin bridging in 29%. The median time of NOAC interruption was 3 days (2 days before and 1 day after the procedure). Major cardiovascular event rates were similar for those with and without heparin bridging (1.6% vs 0.8%, P = NS), but major bleeding complications were higher with heparin bridging (2.27% vs 0.5%, P = 0.01). However, on multivariate analysis, major procedures were independently associated with major bleeding (odds ratio [OR], 16.8; P < 0.001), but heparin bridging, which was more commonly used with major procedures, was not. The authors concluded that continuation or brief interruptions in NOAC therapy for most procedures is safe, but heparin bridging may be useful in selected high-risk patients.

COMMENTARY

This is the first report of the use of NOACs peri-procedurally and provides reassuring data about their safety and effectiveness. The data are similar to a post-hoc analysis of the RE-LY trial of dabigatran vs warfarin, looking at the patients that had a procedure done. Like the RE-LY analysis, this study shows low cardiovascular event rates, which in RE-LY were similar to warfarin. However, this study shows lower major bleeding rates (1.2%) vs RE-LY (4-5%), despite the fact that heparin bridging rates were higher in this study (30%) vs RE-LY (16%). Whether this difference is just due to the different study designs or to the different drugs used is unknown. RE-LY used dabigatran and this registry mainly represented rivaroxaban use (76%) with some dabigatran (23%) and apixaban use (1%).

The data on heparin bridging were also informative in that it did not reduce thromboembolic events, but did seem to increase major bleeding events. These results are somewhat similar to a meta-analysis of warfarin use with heparin bridging that showed reduced thromboembolic events, but increased bleeding (OR = 5). Thus, heparin bridging has been questioned recently. In this study, heparin bridging increased the absolute major bleeding rate, but it was not an independent factor in the multivariate analysis by the authors’ definition. A major surgical procedure was the strongest predictor of major bleeding (OR, 16.8; P < 0.001); whereas heparin bridging was second (OR, 5; P = 0.02). So, concern about the bleeding risks of heparin bridging with NOACs persists and the authors suggest a case-by-case approach. In practice, the main reason to heparin bridge on warfarin therapy has been mechanical prosthetic valves, but NOACs are not indicated for this use, so presumably were not used for such patients in this German study. Thus, the need for heparin bridging with NOACs should be infrequent.

The limitations of this study are that it is observational. Also, the physicians were given no instructions on how to use NOACs. So there could be selection biases. In addition, event rates were low, especially for death. The strengths of the study include the large number of procedures (863), central adjudication of events, and a low rate of lost to follow-up (1%). Thus, until randomized trials are done (unlikely), this study represents the best current data we have on the use of NOACs peri-procedurally. It suggests that it is safe to either continue NOACs for more minor procedures or briefly stop them for more major procedures, and that heparin bridging is usually not needed and may increase bleeding risks.