What is the appropriate anticoagulation regimen for a patient with a history of Deep Vein Thrombosis (DVT) and current bilateral Pulmonary Embolism (PE) on Eliquis (apixaban)?

Management of Bilateral Pulmonary Embolism in a Patient with History of DVT on Apixaban

For a patient with bilateral pulmonary embolism and history of DVT 2 years ago who is currently on Eliquis (apixaban), continuing apixaban at the standard dose of 5 mg twice daily indefinitely is recommended, with consideration for dose reduction to 2.5 mg twice daily after 6 months of therapeutic anticoagulation.

Initial Management of Bilateral PE

• Apixaban is an appropriate choice for the treatment of bilateral PE in a patient with history of DVT, as it has been shown to be non-inferior to conventional therapy (LMWH/warfarin) for the treatment of VTE with a better safety profile 1.
• The standard dosing regimen for acute PE treatment with apixaban is 10 mg twice daily for the first 7 days, followed by 5 mg twice daily 2.
• Since the patient is already on apixaban, the clinician should ensure they are receiving the appropriate therapeutic dose for acute PE treatment 1, 2.

Duration of Anticoagulation

• This patient has recurrent VTE (previous DVT and now bilateral PE), which is considered an unprovoked event in the absence of any mentioned transient risk factors 1.
• For patients with recurrent VTE not related to a major transient or reversible risk factor, oral anticoagulant treatment of indefinite duration is strongly recommended (Class I, Level B recommendation) 1.
• The 2020 American Society of Hematology guidelines also recommend therapeutic anticoagulation for >3 months for all patients with PE, with indefinite continuation for those with recurrent VTE 1.

Choice of Anticoagulant

• Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for VTE treatment (conditional recommendation based on moderate certainty in evidence) 1.
• Apixaban has demonstrated efficacy in preventing recurrent VTE with a favorable bleeding profile compared to conventional therapy 2, 3.
• In the AMPLIFY study, apixaban showed non-inferiority to enoxaparin/warfarin for recurrent symptomatic VTE with lower rates of major bleeding 2, 4.
• For patients with cancer-associated VTE, apixaban has been shown to be non-inferior to dalteparin without increased risk of major bleeding 5.

Extended Therapy Considerations

• After completing the initial 6 months of therapeutic anticoagulation, consider reducing the apixaban dose to 2.5 mg twice daily for extended therapy 1.
• The reduced dose of apixaban (2.5 mg twice daily) has been shown to be effective for extended VTE prevention while potentially reducing bleeding risk (Class IIa, Level A recommendation) 1.
• The ASH guideline panel suggests that either standard-dose or lower-dose DOAC regimens may be used for secondary prevention of VTE (conditional recommendation based on moderate certainty evidence) 1.

Monitoring and Follow-up

• Regular reassessment of drug tolerance, adherence, hepatic and renal function, and bleeding risk is recommended for patients on extended anticoagulation (Class I, Level C recommendation) 1.
• Routine re-evaluation of patients 3-6 months after acute PE is recommended to assess for chronic complications and appropriateness of continued anticoagulation 1.
• Apixaban should be used with caution in patients with severe hepatic impairment as it is primarily metabolized in the liver 1.

Special Considerations

• If the patient has severe renal impairment (creatinine clearance <30 mL/min), apixaban may not be the optimal choice, and alternative anticoagulation strategies should be considered 1.
• For patients with gastric or gastroesophageal tumors, LMWHs are preferred over DOACs due to increased risk of hemorrhage 1.
• If breakthrough VTE occurs while on therapeutic apixaban, consider switching to LMWH rather than another DOAC (conditional recommendation based on very low certainty evidence) 1.

Common Pitfalls to Avoid

• Avoid premature discontinuation of anticoagulation in patients with recurrent VTE, as this significantly increases the risk of another recurrence 1.
• Do not reduce the dose of apixaban before completing the initial 6 months of therapeutic anticoagulation 1.
• Avoid using NOACs in patients with antiphospholipid antibody syndrome, for whom VKA therapy is recommended 1.
• Be cautious about drug interactions, particularly with medications that are strong inhibitors of both CYP3A4 and P-glycoprotein, which can increase apixaban levels 1, 6.