More Bleeding With the Newer Anticoagulants?

Abstract

The new oral anticoagulants that are currently available are dabigatran (Pradaxa, Boehringer Ingelheim), a direct thrombin inhibitor, and the activated factor X (Xa) inhibitors, apixaban (Eliquis, Pfizer) and rivaroxaban (Xarelto, Bayer), with several other agents in the pipeline. These new oral anticoagulants are supposed to have a wider therapeutic window than warfarin, leading to a lower incidence of major bleeding. However, the results of large randomized trials indicate that bleeding remains a major concern even with the new agents. Studies with rivaroxaban, edoxaban and dabigatran showed that these drugs have incidences of severe bleeding comparable to those of enoxaparin and warfarin. The number of bleeding events is rising due to the ageing of the population and the increasing need for interventional therapies. The shorter half-life of the new agents might facilitate the management of bleeding events and the control of anticoagulation during interventions or emergency circumstances. If bleeding occurs, the lack of specific antidotes limits the therapeutic options. Due to the selection bias in the initial randomized studies, the absolute bleeding risk might be underestimated. This can only be measured after exposure of the drugs to larger populations with close post marketing surveillance within registries, a strategy that would be very helpful in defining the actual bleeding risk for the new drug classes. In case of bleeding occurrence, supportive care should be sufficient for most patients because of the short duration of action of the new agents. Some have suggested the use of prothrombin complex concentrates as a reversal agent for the new agents, but the data are limited... (excerpt)