Possible failure of novel direct-acting oral anticoagulants in management of pulmonary embolism: a case report

Abstract

BackgroundThe relative effectiveness of vitamin K antagonists compared with novel oral anticoagulants in treating pulmonary embolism remains unclear. Recent trials comparing the efficacy of vitamin K antagonists with factor Xa inhibitors for the treatment of pulmonary emboli have been non-inferiority studies based primarily on risk reduction (such as bleeding events), rather than resolution of specific diseases such as pulmonary embolism. Consequently, there is a lack of evidence indicating which of these agents are more effective. Here, we present a case where pulmonary emboli were treated with novel oral anticoagulants followed by warfarin to discuss the potential limitations in the use of novel oral anticoagulants as prevention or treatment of thromboembolism and the continued role for warfarin in this setting.Case presentationA 34-year-old African American woman presented to our clinic with shortness of breath and pleuritic chest pain several months post-surgery. She was identified as having multiple bilateral pulmonary embolisms and was treated with several novel oral anticoagulants, which failed to resolve the clots. Complete resolution was achieved upon switching to warfarin.ConclusionsThe patient described in this report failed to respond to novel oral anticoagulant therapy, but her emboli resolved when she was treated with warfarin. This study challenges the notion that factor Xa inhibitors are better alternatives to vitamin K anticoagulants in the treatment of pulmonary emboli based on their safety profile and ease of use alone. As a result, further post-marketing investigations into the efficacy of these agents in the management of pulmonary emboli may be warranted.

Non-vitamin K Oral Anticoagulants and Anti-seizure Medications: A Retrospective Cohort Study

“…In addition, carbamazepine, phenobarbital, phenytoin, and valproic acid have been shown to be able to induce both CYP3A4 and P-GP, although the effect varies in different models (11)(12)(13)(14)(15)(16)(17)(18). Critical DDIs may be associated with failure of the anticoagulation effect and expose the patients to the risk of recurrent stroke and systemic embolism (19,20). On the other hand, switching ASMs to avoid DDIs has been associated with a 16.7-21.7% increased risk in 6-month seizure recurrence rate (21,22).…”

Incomplete Resolution of Deep Vein Thromboses during Rivaroxaban Therapy

“…The recent addition of factor Xa inhibitors to anticoagulant agents is not without fault (i.e., failure, bleeding, and lack of reversal agents), as demonstrated in this case report and other papers [6, 7, 12]. The risk factors for failure of anticoagulation therapy are vast and vary from patient to patient; pharmacodynamics, pharmacokinetics, metabolism, and elimination all have a hand in how a drug interacts in a given patient and are further discussed below [13–15].…”

“…A thorough literature review revealed little in the way of reports of rivaroxaban failure in the treatment of DVT, although a few case reports in which potential rivaroxaban failure is noted have emerged recently [6, 7]. Postmarketing surveillance is clearly an important factor in the further development, safety, and efficacy of any novel drug.…”

“…On the other hand, rivaroxaban's disadvantages have been documented as well. The major disadvantages include internal bleeding, particularly gastrointestinal bleeding [5], as well as documented cases in which thromboembolisms do not completely resolve [6, 7]. …”

Venous Thromboembolism While on Anticoagulation With Apixaban

“…Treatment failure of thromboembolism was previously mentioned in the literature, with an incidence rate of 2% [ 12 - 13 ]. One case report published in 2016, of a patient treated with different classes of DOACs, failed to resolve pulmonary clots who needed final treatment with warfarin [ 14 ]. Another case was reported in 2017 with recurrence of DVT while on apixaban.…”