How to transition a cancer patient with pulmonary embolism from injectable (Low Molecular Weight) heparin to an oral anticoagulant, such as apixaban (Apixaban) or rivaroxaban (Rivaroxaban)?

Transitioning Cancer Patients with Pulmonary Embolism from Injectable Heparin to Oral Anticoagulation

For cancer patients with pulmonary embolism, you can transition directly from LMWH to apixaban or rivaroxaban without bridging, using the specific loading dose regimens for each agent. 1

Direct Transition Protocol

For Apixaban

• Start apixaban 10 mg orally twice daily for the first 7 days, then reduce to 5 mg twice daily 1, 2
• Discontinue LMWH and begin apixaban at the time the next LMWH dose would have been given 2
• No bridging or overlap period is required 2

For Rivaroxaban

• Start rivaroxaban 15 mg orally twice daily for the first 21 days, then reduce to 20 mg once daily 1
• Discontinue LMWH and begin rivaroxaban at the time the next LMWH dose would have been given 3
• No bridging or overlap period is required 3

For Edoxaban (Alternative Option)

• Requires 5 days of continued LMWH before starting edoxaban 60 mg once daily 1
• This is the only direct oral anticoagulant that requires overlap with parenteral therapy 1

Evidence Supporting Direct Oral Anticoagulants in Cancer

The 2022 International Society on Thrombosis and Haemostasis guidelines upgraded the recommendation for direct oral anticoagulants (including apixaban) from grade 1B to grade 1A based on four randomized clinical trials (ADAM-VTE, CARAVAGGIO, and CANVAS) demonstrating non-inferiority to LMWH for recurrent VTE and mortality outcomes 1. The CARAVAGGIO trial specifically showed apixaban was noninferior to dalteparin (5.6% vs 7.9% recurrent VTE) without increased major bleeding risk (3.8% vs 4.0%) 4.

The choice between LMWH continuation and oral anticoagulants (edoxaban or rivaroxaban) is left to physician discretion and patient preference according to the 2019 European Society of Cardiology guidelines 1.

Critical Exclusion Criteria

Do NOT transition to oral anticoagulants if the patient has:

• High risk of gastrointestinal or genitourinary bleeding 1
• Creatinine clearance <30 mL/min 1, 2
• Active gastrointestinal malignancy with mucosal involvement 1

For these patients, continue LMWH monotherapy indefinitely 1, 5.

Duration of Anticoagulation

Cancer patients should receive indefinite anticoagulation after a first episode of VTE due to high recurrence risk 1. The 2019 ESC guidelines emphasize that patients with cancer have particularly high VTE recurrence risk in the absence of anticoagulation, and treatment should continue as long as cancer remains active 1.

After the first 6 months of therapeutic anticoagulation, periodic reassessment of the risk-to-benefit ratio is mandatory, considering success of anticancer therapy, estimated VTE recurrence risk, bleeding risk, and patient preference 1.

Practical Implementation

• Ensure renal function is adequate (CrCl ≥30 mL/min) before prescribing 1, 2
• Assess bleeding risk using validated prediction models 1
• Educate patients on the loading dose regimen and when to transition to maintenance dosing 2
• For patients unable to swallow tablets, apixaban can be crushed and suspended in water, D5W, or apple juice 2
• Schedule follow-up to reassess drug tolerance, adherence, hepatic/renal function, and bleeding risk at regular intervals 1