Treatment Failures of Direct Oral Anticoagulants

Use of direct oral anticoagulants (DOACs) has increased over the years, because they have become a safe and effective alternative to the Vitamin-K antagonists in various clinical scenarios. With their increased use, reports have emerged describing their failure.

What are the patient characteristics and clinical settings in which DOAC treatment failure manifests?

We searched published reports in Google Scholar, PubMed, MEDLINE, and Embase from the introduction of DOACs in any therapy until March 2019.

Information on patient characteristics, comorbidities, primary anticoagulation indications, pharmacologic treatment, and outcomes were collected. Primary endpoints were new thrombus formation, failure of resolution of an existing thrombus, or discovery of subtherapeutic drug level. Other endpoints were time to treatment failure, manifestations of treatment failure, and new treatment after DOAC failure.

Our search yielded 51 manuscripts, describing 79 patients who exhibited DOAC failure. The most common treatment failures were in patients with antiphospholipid syndrome (44.3%), atrial fibrillation (30.4%), and deep venous thrombosis (6.3%). There was a trend toward higher failure rate for rivaroxaban (65.8%) followed by dabigatran (27.8%), apixaban (7.6%), and then edoxaban (1.3%). Each agent had different median failure times. Most common manifestations of treatment failure were stroke/transient ischemic attack (20.3%), pulmonary embolism (19.0%), and deep venous thrombosis (19.0%). More than half of patients were transitioned to a Vitamin-K antagonist after DOAC failure (55.7%).

Our analysis illustrates that DOACs may fail in the setting of Food and Drug Administration and non-Food and Drug Administration- approved indications. In clinical practice, it may be best to choose between available anticoagulant drugs on a case-by-case basis.