Observatory of Invasive Procedures and Bleeding in Patients Treated With New Oral Anticoagulants

The arrival on the market of direct oral factor Xa and factor IIa inhibitors (dabigatran (Pradaxa®), rivaroxaban (Xarelto®), apixaban (Eliquis®) and others soon to come) raises novel questions among clinicians confronted with the emergency management of patients treated with these new drugs. It is likely that these new oral anticoagulants (NOACs) will eventually win a significant market share in the indications secondary prevention of venous thromboembolism and prevention of cardioembolic events in patients with nonvalvular atrial fibrillation, due to their net clinical benefit and their practicality of use compared with vitamin K antagonists (VKAs).

However, despite the fact that NOACs reduce the incidence of intracranial bleeding by about half compared with VKAs, the risk remains significant; furthermore, in clinical trials, these drugs had little or no effect on reducing the incidence of major extracranial bleeding. In everyday practice, where the indication could be expanded to unselected populations and due to a potential for misuse, it is likely that the incidence of bleeding complications will be higher than that reported in clinical trials. Indeed, the numerous alerts emanating from regulatory agencies in various countries (US, Australia, etc.) bear witness to this, and should serve as a reminder that these anticoagulants have a real potential for bleeding complications and, in the absence of an antidote, there is no validated management strategy.

Furthermore, as these drugs can be prescribed for months or years, patients may eventually be exposed to situations at high hemorrhagic risk, such as emergency surgery or invasive procedures, trauma, etc. Analysis of data from the trial : dabigatran versus warfarin in patients with atrial fibrillation (RE-LY) showed that during the two years of follow-up, approximately 25% of the patients underwent an invasive procedure, ranging from pacemaker insertion to major surgery. Thus, a large proportion of patients treated with NOACs are concerned by this issue.

In anticipation of a gradually increasing influx of patients in a critical situation (active bleeding or need to rapidly secure hemostasis before an invasive procedure), it is urgent to define the conduct to adopt based on the experience gained from the earliest cases. This is the objective of the French-speaking GIHP-NACO observatory set up by the GIHP (French Working Group on Perioperative Hemostasis).

For the moment, then, the management recommendations derive from expert opinions based on pharmacokinetic data and on the partial correction of NOAC-induced hypocoagulability by various nonspecific procoagulants (non-activated or activated prothrombin complex concentrates, recombinant factor VIIa). These procoagulants are currently used in an empirical manner to control bleeding, with as many successes as failures reported in the literature, and their benefit-risk ratio in these patients is therefore uncertain.