Pharmacists Must Weigh DOACs’ Benefits Versus Risks

While direct oral anticoagulants (DOACs) provide many benefits for patients with venous thromboembolism (VTE), new research is finding that there are many patients who should not take them.

The article, published in December in the American Journal of Managed Care, provides an overview of current VTE treatment strategies, with an emphasis on DOACs’ place in therapy.

“Although VTE remains a significant burden to morbidity and mortality for hundreds of thousands of U.S. adults, the emergence of DOACs has given patients and health-care providers expanded options for anticoagulation therapy,” wrote Taylor Steuber, PharmD, BCPS, Assistant Clinical Professor at Auburn University’s Harrison School of Pharmacy in Huntsville, AL.

Compared with warfarin, DOACs provide a more predictable anticoagulant response, fewer drug interactions, significantly less risk of hemorrhagic stroke, no monitoring requirements (which means fewer office visits), and shorter half-lives, Steuber wrote. “These benefits have catapulted the demand for DOACs ahead of vitamin K antagonists (VKAs) in oral anticoagulation therapy, and clinical guidelines now recommend these agents over warfarin and other standard therapies in most patients requiring VTE prophylaxis and/or treatment.”

However, even with numerous benefits, there are many patients for whom DOACs are not suitable.

Steuber said that patients with very poor adherence to DOACs should receive VKAs so they can be appropriately monitored, and those who are or who may become pregnant should receive low-molecular-weight heparin therapies. Patients with liver disease, coagulopathy, severe kidney disease, or cancer should not receive DOACs, “and clinicians must always remember to consider cost in the management strategy, as this can impact adherence,” Steuber wrote.

Although a reversal agent is now available for dabigatran, other DOACs lack a specific agent that can be used for reversal in emergency situations, Steuber said. Idarucizumab (Praxbind) is approved for the reversal of dabigatran in emergency surgery, urgent procedures, life-threatening situations, or uncontrolled bleeding. A recent trial in 503 patients confirmed a dabigatran reversal of 100% using idarucizumab, with a median time to cessation of bleeding of 2.5 hours, Steuber noted.

Another promising reversal agent is andexanet alfa, a recombinant modified human factor Xa decoy protein that reverses the effects of both direct and indirect factor Xa inhibitors such as rivaroxaban (Xarelto) and low-molecular-weight heparin.

Andexanet alfa is currently the subject of a Phase 3 clinical trial. In addition, a multicenter prospective study evaluated 67 patients who had acute major bleeding within 18 hours after administration of rivaroxaban or apixaban (Eliquis). After administration of andexanet alfa, the median anti-Xa factor activity decreased by 89% and 93% for patients taking apixaban and rivaroxaban, respectively.