Caravaggio
(2020)Objective
To assess whether oral apixaban would be noninferior to subcutaneous dalteparin for the prevention of recurrent venous thromboembolism in patients with cancer without increasing the risk of major bleeding
Study Summary
• Recurrent VTE occurred in 5.6% with apixaban vs 7.9% with dalteparin (HR 0.63)
• Major bleeding rates were similar between groups (3.8% vs 4.0%)
Intervention
Oral apixaban (10 mg twice daily for 7 days, then 5 mg twice daily) vs subcutaneous dalteparin (200 IU/kg daily for 1 month, then 150 IU/kg daily)
Inclusion Criteria
Adults with cancer who had newly diagnosed symptomatic or incidental proximal deep-vein thrombosis or pulmonary embolism
Study Design
Arms: Apixaban group vs Dalteparin group
Patients per Arm: 576 vs 579
Outcome
• Safety: Major bleeding - 3.8% vs 4.0% (similar)
• Combined endpoint: VTE or major bleeding - 8.9% vs 11.4%
Bottom Line
Oral apixaban was noninferior to subcutaneous dalteparin for treating cancer-associated venous thromboembolism with similar major bleeding rates, offering a convenient oral alternative to subcutaneous therapy.
Major Points
- Multinational, open-label, noninferiority trial comparing apixaban to dalteparin in cancer patients with VTE
- Primary endpoint of recurrent VTE met noninferiority criteria (5.6% vs 7.9%, HR 0.63)
- Major bleeding rates were similar between groups (3.8% vs 4.0%)
- Study included patients with predominantly advanced active cancer
- Apixaban offers oral convenience compared to daily subcutaneous injections
Study Design
- Study Type
- Multinational, randomized, investigator-initiated, open-label, noninferiority trial
- Randomization
- Yes
- Blinding
- Open-label with blinded central outcome adjudication
- Sample Size
- 1155
- Follow-up
- 6 months
- Centers
- 119
- Countries
- Italy, France, Spain, Netherlands, United Kingdom, Germany, Israel, United States, Poland
Primary Outcome
Definition: Objectively confirmed recurrent venous thromboembolism during 6-month trial period
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 46/579 (7.9%) | 32/576 (5.6%) | 0.63 (0.37-1.07) | <0.001 for noninferiority; 0.09 for superiority |
Limitations & Criticisms
- Open-label design could introduce bias
- Not powered to make definitive conclusions about bleeding outcomes
- Excluded patients with brain tumors, cerebral metastases, or acute leukemia limiting generalizability
- Gastrointestinal bleeding was not a prespecified outcome
- Subgroup finding of decreased efficacy with increasing age should be considered hypothesis-generating
Citation
N Engl J Med 2020;382:1599-607