Key Points:
- Venous thromboembolism (VTE) is a leading cause of mortality in cancer patients
- Extended anticoagulation is recommended for cancer patients with VTE, but balancing efficacy and bleeding risk remains a challenge.
- The API-CAT trial demonstrated that extended reduced-dose apixaban (2.5 mg twice daily) was non-inferior to full-dose apixaban (5 mg twice daily) in preventing VTE recurrence while significantly lowering bleeding risk.
Venous thromboembolism (VTE) is a frequent complication in cancer patients and the second most common cause of death in this population after cancer itself. The increased risk of clot formation among patient with cancer is multifactorial: cancer cells promote thrombosis, cancer treatments induce vascular inflammation, and factors such as surgery, limited mobility, and invasive medical devices further elevate VTE risk. Current guidelines recommend anticoagulation for at least six months in patients with cancer-associated VTE, with continued treatment advised for as long as the cancer remains active or cancer therapy is ongoing. However, prolonged anticoagulation increases bleeding risk, leaving uncertainty about the optimal dosing strategy beyond the initial treatment period.
To address this gap, Professor Isabelle Mahé, MD, PhD, from Université Paris Cité, presented findings from the API-CAT trial at the 2025 American College of Cardiology’s Annual Scientific Conference during a Late-Breaking Clinical Trials session, with simultaneous publication in The New England Journal of Medicine. This investigator-sponsored study, funded by the Bristol-Myers Squibb-Pfizer Alliance, evaluated whether a lower dose of apixaban could provide comparable efficacy to the full dose in preventing recurrent VTE while reducing bleeding risk in cancer patients who had already completed at least six months of anticoagulation therapy.
In this randomized, double-blind, international trial, 1,766 patients with active cancer were enrolled across 11 countries. Participants, with a median age of 67 years, were randomized to receive either reduced-dose apixaban (2.5 mg twice daily) or full-dose apixaban (5 mg twice daily) for an additional 12 months following their initial six-month anticoagulant treatment period. The primary endpoint was the recurrence of VTE or VTE-related death, while the key secondary endpoint assessed major bleeding and clinically relevant bleeding requiring medical intervention.
At 12 months, VTE recurrence was observed in 18 patients in the reduced-dose group and 24 patients in the full-dose group (cumulative incidence: 2.1% vs. 2.8%), meeting the pre-specified criteria for non-inferiority. Clinically relevant bleeding occurred in 102 patients receiving the reduced dose compared to 136 in the full-dose group (cumulative incidence: 12.1% vs. 15.6%), indicating a significant reduction in bleeding risk with the lower dose. Mortality rates were comparable between the groups (17.7% vs. 19.6%).
Discussing the trial results, Professor Mahé stated, “We can now confidently say that lower-dose apixaban is both effective and safer than the full dose for extended anticoagulation in cancer patients with VTE.” She added, “These findings should lead to an update in clinical guidelines recommending reduced-dose anticoagulation for this population.”
Despite the positive findings, the study had limitations. The optimal duration of anticoagulation beyond the 12-month follow-up remains unclear. Additionally, as France does not permit the collection of racial and ethnic data, potential differences in safety and efficacy across diverse patient populations could not be assessed. Patients with brain tumors were also excluded, limiting the applicability of findings to this subgroup.