The market for oral anticoagulants has advanced significantly since warfarin was essentially the lone option. Still, in some cases, the use of improved direct oral anticoagulants (DOACs) can provoke uncontrolled bleeding in patients. Healthcare professionals need a discerning approach to selecting anticoagulation reversal agents.
Becker's Hospital Review recently spoke with Paul P. Dobesh, PharmD, professor of pharmacy practice and science at University of Nebraska Medical Center College of Pharmacy in Omaha, about the importance of matching the right reversal agent to the right anticoagulant in patients who experience uncontrolled or life-threatening bleeding.
Direct oral anticoagulants are widely used, essential medications but come with risks
For about five decades, warfarin dominated the oral anticoagulant market and was the most widely used drug in the category, despite its multiple negative side effects, most notably, bleeding.
Beginning around 2010, warfarin was gradually displaced by a new generation of DOACs, including dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa). The safety of these DOACs in reducing bleeding events is stronger and more predictable than that of warfarin and their intake requires fewer restrictions around diet and monitoring.
Nevertheless, despite DOACs' significantly lower incidence of intracranial hemorrhage — a major bleed risk associated with the use of oral anticoagulants — compared to warfarin, such hemorrhages still do occur on occasion. When they do, the mortality rate of both DOACs and warfarin hovers just under 50 percent at 30 days.
Anticoagulation reversal agents are an antidote to some, but not all, DOACs
The conventional method of reversing warfarin-induced major bleeds was fresh frozen plasma (FFP). Now, four factor prothrombin complex concentrate (4F-PCC) are preferred for warfarin-induced bleeding over FFP, due to their much faster reversal from needing to give less volume over time. Since 4F-PCC is about 30-fold more concentrated in providing needed clotting factors, only about 200 milliliters are necessary compared to a couple of liters of plasma. Unfortunately, 4F-PCC is not effective for the reversal of factor Xa (FXa) inhibitors such as apixaban and rivaroxaban
FXa inhibitor-related bleeding requires specific reversal agents
As healthcare leaders come to terms with the fact that 4F-PCC is not effective for the reversal of FXa inhibitor-related bleeding, they are beginning to develop evidence-based practice guidelines and protocols for assigning a specific reversal agent for each anticoagulant. It is essential that organizations develop and use these guidelines to establish which reversal agents are appropriate for which clinical situation.
"We just presented data at the International Society of Thrombosis and Haemostasis . . . where using andexanet alfa was associated with a 31 percent reduction in hospital mortality, compared to that of patients getting 4F- PCC to reverse the same agents," Dr. Dobesh said, referring to the only FDA-approved agent for reversal of FXa-related bleeding (brand name ANDEXXA). "What we're going to be seeing in the future is [providers] trying to make sure we're using the right drug for the right setting."
Conclusion
As the market for anticoagulation reversal agents expands, and as understanding of their mechanism of action advances and providers become more discerning about matching the right agent to the right DOAC, providers will have more and better options to effectively treat patients who experience life-threatening anticoagulant-induced bleeding