An international, prospective, double-blind, non-inferiority Apixaban Cancer Associated Thrombosis (API-CAT) study showed that a reduced-dose regimen of apixaban (2.5 mg twice daily) was non-inferior to a full-dose regimen (5 mg twice daily) with regard to the prevention of recurrent venous thromboembolism (VTE) in patients with active cancer who had completed at least 6 months of anticoagulant treatment for proximal deep-vein thrombosis (DVT) or pulmonary embolism (PE).
In addition, the incidence of clinically relevant bleeding was lower with the reduced-dose than with the full-dose regimen. The findings were published by Dr. Isabelle Mahé of the Hôpital Louis Mourier, Service de Médecine Interne, Assistance Publique–Hôpitaux de Paris, Université Paris Cité in Colombes, France and colleagues on 29 March 2025 in The New England Journal of Medicine.
The authors wrote in the background that patients with cancer are at higher risk for VTE than the general population. Patients with cancer-associated VTE are at greater risk for recurrent events despite anticoagulant therapy and for bleeding complications than patients with VTE who do not have cancer. Anticoagulation with a direct oral anticoagulant or low-molecular-weight heparin is recommended for an initial period of 6 months.
Patients with active cancer remain at risk for recurrent VTE if anticoagulant therapy is stopped after the initial treatment. Clinical practice guidelines suggest that anticoagulant therapy be continued for as long as the cancer remains active or cancer treatment is ongoing, but clinicians need to balance the benefits of anticoagulant therapy with the risk of bleeding complications, which persist over time.
Owing to limited data from randomised studies, appropriate and effective regimens of anticoagulant therapy beyond the initial 6 months have been unclear. In API-CAT study the investigators assessed whether a reduced-dose regimen of apixaban (2.5 mg twice daily) would be non-inferior to a full-dose regimen (5 mg twice daily) for the prevention of recurrent VTE in patients with active cancer who had completed at least 6 months of anticoagulant therapy for proximal DVT or PE.
Consecutive patients with active cancer and proximal DVT or PE, who had completed at least 6 months of anticoagulant therapy, were randomly assigned in a 1:1 ratio to receive oral apixaban at a reduced (2.5 mg) or full (5 mg) dose twice daily for 12 months. The primary outcome was centrally adjudicated fatal or non-fatal recurrent VTE, assessed in a non-inferiority analysis (margin of 2.00 for the upper boundary of the 95% confidence interval [CI] of the subhazard ratio). The key secondary outcome was clinically relevant bleeding, assessed in a superiority analysis.
A total of 1766 patients underwent randomisation at a median time since the index event of 8.0 months (interquartile range 6.5 to 12.6); 866 patients were assigned to the reduced-dose group, and 900 to the full-dose group. The median treatment duration was 11.8 months (interquartile range, 8.3 to 12.1). Recurrent VTE occurred in 18 patients (cumulative incidence 2.1%) in the reduced-dose group and in 24 (cumulative incidence 2.8%) in the full-dose group (adjusted subhazard ratio 0.76; 95% CI 0.41 to 1.41; p = 0.001 for non-inferiority).
Clinically relevant bleeding occurred in 102 patients (cumulative incidence 12.1%) in the reduced-dose group and in 136 (cumulative incidence 15.6%) in the full-dose group (adjusted subhazard ratio 0.75; 95% CI 0.58 to 0.97; p = 0.03). Mortality was 17.7% in the reduced-dose group and 19.6% in the full-dose group (adjusted hazard ratio 0.96; 95% CI 0.86 to 1.06).
In an accompanied editorial, Dr. Simon Noble of the Cardiff University in Cardiff, UK wrote that much has changed since the CLOT study established a 6-month course of weight-adjusted low-molecular-weight heparin as standard-of-care for CAT. Direct oral anticoagulants apixaban, edoxaban, and rivaroxaban have shown non-inferiority to the low-molecular-weight heparins in terms of efficacy. Furthermore, advances in oncology have led to improved survival among patients with many cancer types, such that they are living longer with metastatic disease while continuing to receive systemic anticancer therapies.
Rise in the prevalence of VTA is nearly in parallel with the increased use of novel anticancer agents. However, data are lacking to inform clinical guidelines on extending anticoagulant treatment beyond 6 months. The presence of ongoing active cancer or anticancer treatments provides a strong case for continued anticoagulation; but, the appropriate dose for preventing recurrent thrombosis while minimising the risk of bleeding is unknown.
The reduced incidence of bleeding observed in the reduced-dose group in API-CAT study, without an increase in the incidence of recurrent VTE, establishes apixaban, administered at a 2.5 mg twice daily dose, as an appropriate regimen for anticoagulation beyond the first 6 months in patients with cancer according to the editorialist.
The study was supported by the Bristol-Myers Squibb–Pfizer Alliance.
References
- Mahé I, Carrier M, Mayeur D, et al. for the API-CAT Investigators. Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism. N Engl J Med 2025;392:1363-1373.
- Noble S. Cancer-Associated Venous Thromboembolism — Beyond 6 Months. N Engl J Med 2025;392:1439-1440.