Phase 3 results on extending anticoagulant treatment with half-dose apixaban in active cancer
ACC.25 – In the API-CAT trial, apixaban 2.5 mg twice daily was noninferior to 5 mg twice daily in preventing recurrent venous thromboembolism (VTE) and reduced bleeding in patients with cancer-associated VTE who had completed ≥6 months of anticoagulant treatment.
This summary is based on the presentation of Isabelle Mahé, MD, PhD (Paris, France) at the ACC.25 Scientific Session - Extended Anticoagulant Treatment With A Reduced Versus Full Dose Apixaban In Patients With Cancer-associated Venous Thromboembolism: The API-CAT Study.
Introduction and methods
Although the risk of recurrent venous thromboembolism (VTE) decreases over time in patients with active cancer and VTE, the risk of bleeding is still considerable. Clinical guidelines recommend continuing anticoagulant therapy for as long as the cancer is active or cancer treatment is ongoing. However, it is unknown whether a reduced dose of an oral anticoagulant is effective in preventing recurrent thromboembolic events and decreasing bleeding risk.
The API-CAT (APIxaban Cancer-Associated Thrombosis) trial was an international, investigator-initiated, double-blind, noninferiority, phase 3 RCT with blinded central outcome adjudication. In this study, 1766 consecutive patients with active cancer and VTE (i.e., proximal deep-vein thrombosis of lower limb or symptomatic or incidental pulmonary embolism) who had completed ≥6 months of anticoagulant treatment were randomized to oral apixaban 5 mg twice daily or a reduced dose of 2.5 mg twice daily, both for 12 months. Median time between the index VTE event and randomization was 8.0 months (IQR: 6.5–12.6), and median treatment duration was 11.8 months (IQR: 8.3–12.1).
The primary efficacy endpoint was centrally adjudicated recurrent (fatal or nonfatal) VTE according to a noninferiority analysis (prespecified noninferiority margin for upper limit of 95%CI for subdistribution HR: 2.00). The key secondary safety endpoint was clinically relevant bleeding, defined as a composite outcome of adjudicated major or clinically relevant nonmajor bleeding, which was assessed in a superiority analysis.
Main results
- Recurrent VTE occurred in 18 patients (2.1%) treated with the reduced dose of apixaban and 24 patients (2.8%) receiving the full dose (adjusted subdistribution HR: 0.76; 95%CI: 0.41–1.41; P=0.001 for noninferiority).
- The frequency of clinically relevant bleeding was 12.1% in the reduced-dose group and 15.6% in the full-dose group (adjusted subdistribution HR: 0.75; 95%CI: 0.58–0.97; P=0.03 for superiority).
- There was no difference in the incidence rate of all-cause mortality between the reduced-dose and full-dose groups (17.7% vs. 19.6%; adjusted HR: 0.96; 95%CI: 0.86–1.06).
Conclusion
The API-CAT trial showed that reduced-dose apixaban (2.5 mg twice daily) was noninferior to full-dose apixaban (5 mg twice daily) in preventing recurrent VTE in patients with active cancer and VTE who had completed ≥6 months of anticoagulant treatment. Treatment with the reduced dose also resulted in a decreased risk of clinically relevant bleeding.
- Our reporting is based on the information provided at the ACC.25 Scientific Session -