What is the next step for a patient with failure of outpatient anticoagulation therapy on Eliquis (apixaban) with persistent and new deep vein thrombosis (DVT)?

From the Guidelines

For a patient with failure of outpatient therapy on Eliquis (apixaban) with persistent and new DVT, I recommend switching to low molecular weight heparin (LMWH) such as enoxaparin (Lovenox) at a therapeutic dose of 1 mg/kg twice daily subcutaneously, as suggested by the American Society of Hematology 2020 guidelines for management of venous thromboembolism 1. This approach is supported by the guidelines, which recommend considering LMWH for patients who require medications that are inhibitors or inducers of P-glycoprotein, or strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) enzymes, and for patients with renal and/or hepatic insufficiency. The patient should be evaluated for potential causes of anticoagulation failure, including:

• Medication non-adherence
• Drug interactions
• Cancer
• Antiphospholipid syndrome
• Anatomical issues causing venous compression Laboratory testing for these conditions should be performed, as recommended by the Chest guideline and expert panel report 1. The failure of Eliquis suggests that either the drug is not achieving adequate anticoagulation in this specific patient or there are underlying factors making the clot resistant to standard therapy. LMWH has a different mechanism of action and pharmacokinetics compared to direct oral anticoagulants like Eliquis, which may provide more reliable anticoagulation in patients with recurrent thrombosis, as suggested by the Chest guideline and expert panel report 1. The patient should be monitored with repeat ultrasounds to assess clot resolution and should be considered for referral to a hematologist or vascular specialist for comprehensive evaluation of this treatment failure. Alternatively, consider warfarin with a target INR of 2-3 after an initial 5-day overlap with LMWH, as recommended by the American Society of Hematology 2020 guidelines for management of venous thromboembolism 1.

From the FDA Drug Label

1.5 Reduction in the Risk of Recurrence of DVT and PE Apixaban tablets are indicated to reduce the risk of recurrent DVT and PE following initial therapy.

2.4 Converting from or to apixaban Switching from apixaban to anticoagulants other than warfarin (oral or parenteral): Discontinue apixaban and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of apixaban

The next step for a patient with failure of outpatient anticoagulation therapy on Eliquis (apixaban) with persistent and new deep vein thrombosis (DVT) is to discontinue apixaban and switch to a different anticoagulant. The choice of the new anticoagulant should be determined by the patient's healthcare provider, considering the individual's medical history, current condition, and other factors. 2

From the Research

Next Steps for Patients with Failure of Outpatient Anticoagulation Therapy on Eliquis (Apixaban)

• For patients experiencing failure of outpatient anticoagulation therapy on Eliquis (apixaban) with persistent and new deep vein thrombosis (DVT), the next steps are not clearly defined, but several options can be considered 3, 4, 5.
• A study published in the Journal of Thrombosis and Thrombolysis found that patients who experienced recurrent thrombosis while on apixaban or rivaroxaban were subsequently treated with warfarin, dabigatran, or enoxaparin, with no significant difference in outcomes among these groups 3.
• Another study published in the Journal of Thrombosis and Thrombolysis found that patients who experienced treatment failure with a direct oral anticoagulant (DOAC) were often temporarily switched to therapeutic-dose low molecular weight heparin, and then returned to oral anticoagulation, with most experiencing no further treatment failures 4.
• A review of treatment failures of DOACs published in the American Journal of Therapeutics found that the most common manifestations of treatment failure were stroke/transient ischemic attack, pulmonary embolism, and deep venous thrombosis, and that more than half of patients were transitioned to a Vitamin-K antagonist after DOAC failure 5.

Considerations for Choosing the Next Anticoagulant

• The choice of next anticoagulant should be based on patient-specific factors, such as comorbidities, primary anticoagulation indications, and pharmacologic treatment history 3, 5.
• The use of enoxaparin may be preferred in patients with a malignancy-associated etiology for recurrent thrombosis 3.
• The choice of anticoagulant should also consider the patient's risk of bleeding and thrombosis, as well as their ability to adhere to the treatment regimen 6.

Monitoring and Follow-up

• Patients who experience failure of outpatient anticoagulation therapy on Eliquis (apixaban) should be closely monitored for signs and symptoms of recurrent thrombosis or bleeding complications 3, 4, 5.
• Regular follow-up appointments with a healthcare provider are necessary to adjust the treatment plan as needed and to minimize the risk of adverse outcomes 6.