Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry

Beyer-Westendorf J, Gelbricht V, Förster K
Eur Heart J. 2014 Jan 6. [Epub ahead of print]

Background

Patients on vitamin K antagonists (VKAs) who needed to undergo surgical or interventional procedures, had to temporarily discontinue VKA therapy. It is often interrupted for 5-7 days before the procedure [1]. After re-initiation, it may take another 5-7 days before the therapeutic international normalised ratio will be achieved. Often bridging therapy with low-molecular-weight heparin (LMWH) is given throughout this period [1-3]. Recent insights suggest that this may increase the risk of peri-procedural bleeding complications, although it is effective in preventing thrombo-embolic complications [2].
The novel oral anticoagulants (NOACs) have shorter half-lives than VKA, thus the interval of pre-procedural interruption may be reduced to 1 or 2 days, and anticoagulant activity can be restored quicker. Expert opinions have recommended against heparin bridging for patients on NOACs undergoing interventional procedures [4-6], although scientific evidence is lacking for such recommendations.
Using data from a large, regional, prospective NOAC registry, this study evaluated the management and safety of peri-interventional NOAC use in a large cohort of patients from daily care (Dresden NOAC registry). A total of 863 surgical or interventional procedures were documented during the study period, 595 patients. Most procedures were performed in patients receiving rivaroxaban (n=656, 76%), or dabigatran (n=203, 23.5%), but hardly on apixaban (n=4, 0.5%).

Main results

• Major cardiovascular (CV) events and major bleeding complications were rare in the first 30 +5 days post-procedure (1.0% and 1.2% respectively), most often after major surgery.
  46 bleeding complications were documented (5.3%).
• No significant difference was seen between cohorts with a SPAF or VTE indication for NOAC use with regard to CV events, bleeding complications or fatal outcomes. Neither were differences in those outcomes observed between patients on dabigatran or rivaroxaban.  
• When NOAC was interrupted (276 cases), the median duration of the NOAC-free interval was 2 days (IQR: 2) before the procedure, and 1 (IQR 3) day after the procedure.
  Use of heparin bridging increased significantly with the severity of the surgical procedure (10.4, 27.8 and 74.7% for minimal, minor and major surgery, P<0.001).
• Rates of major CV events were similar for patients without heparin bridging (NOAC continued (n=187) or interrupted (n=419): event rate: 0.8%, 95%CI: 0.3-1.9%) and for those with heparin bridging (event rate: 1.6%, 95%CI: 0.4-3.9, P=0.265).
• Major bleeding complications were more frequent in patients who received heparin bridging (2.7%, 95%CI: 1.1-5.5) as opposed to those who did not (0.5%, 95%CI: 0.1-1.4%, P=0.010).
• A history of diabetes (OR: 13.2, 95%CI: 1.6-107.3, P=0.016) and major procedures (OR: 7.3, 95%CI: 1.9-28.5, P=0.004) were identified as the only independent risk factors for CV events. Heparin bridging did not significantly affect this risk with OR 1.9 (95%CI: 0.5-7.1, P=0.341).
• For major bleeding, major procedures (OR: 16.8, 95%CI: 3.8-78.9, P<0.001) and heparin bridging (OR: 5.0, 95%CI: 1.2-20.4, P=0.023) were the only independent risk factors. It should be noted that heparin bridging was significantly more often used in major procedures, and if corrected for type of procedure, heparin bridging was no longer an independent risk factor for major bleeding.

Conclusion

These are the first available data on the management and outcome of NOAC use in patients undergoing surgical or interventional procedures. Most (78%) procedures were performed with NOAC interruption. Contrary to expert recommendations, about 30% of all procedures were performed with heparin bridging. No specific recommendations were given in this registry, thus treatment regimens were likely decided upon based on the patient’s specific situation.
These results confirm the recommendations of short-term NOAC interruption without heparin bridging, and show that this strategy is safe. No differences were seen in CV event rates, but major bleeding complications were more common after heparin bridging, mostly in patients undergoing major procedures. Benefit evaluation is needed in patients at high CV risk who need to undergo major procedures.

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