API-CAT Trial Shows Reduced-Dose Eliquis Matches Full Dose in Preventing Venous Thromboembolism, Lowers Bleeding Risk in Cancer Patients

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Findings from the Phase III API-CAT trial (NCT03692065) show that extended anticoagulant therapy with reduced-dose Eliquis (apixaban) at 2.5 mg twice daily was noninferior to the full-dose regimen of 5.0 mg twice daily in preventing recurrent venous thromboembolism in patients with active cancer.^1,2 The trial results, published by The New England Journal of Medicine, also show Eliquis significantly lowered the risk of clinically relevant bleeding.

“Treatment guidelines recommend the continuation of anticoagulant therapy for as long as the cancer is active, given that discontinuation is associated with a high risk of recurrent venous thromboembolism,” the study authors wrote. “However, the avoidance of bleeding complications during extended anticoagulant therapy is a key issue that also requires consideration. In the present trial, the incidence of recurrent venous thromboembolism during the 12 months of extended treatment was low in each group, and the reduced dose was not associated with an excess incidence of recurrent events.”¹

Eliquis is an oral anticoagulant indicated to treat patients with nonvalvular atrial fibrillation to lower the risk of stroke and systemic embolism; for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and prophylaxis in DVT that may lead to PE in patients who received knee or hip replacement surgery; and to lower the risk of recurrent DVT and PE following initial therapy.³

“Owing to limited data from randomized trials, appropriate and effective regimens of anticoagulant therapy beyond the initial 6 months have been unclear,” the study authors wrote. “The use of a reduced dose of an oral anticoagulant, which has been suggested for extended treatment in patients without cancer, appears to be an attractive treatment option in the population of patients with cancer but requires specific prospective assessment of its efficacy and safety as compared with a full dose.”¹

Trial Design

The randomized, double-blind, noninferiority API-CAT trial was conducted with a blinded central outcome adjudication. Investigators enrolled 1766 patients with active cancer and proximal DVT or PE who completed at least six months of treatment with anticoagulants. Patients were randomly assigned in a 1:1 ratio to receive oral Eliquis at the reduced 2.5 mg dose (n = 866) or the full 5.0 mg dose (n = 900) twice daily for 12 months.

The trial’s primary endpoint was centrally adjudicated fatal or nonfatal recurrent venous thromboembolism, as assessed in a noninferiority evaluation (margin of 2.00 for the upper boundary of the 95% confidence interval of the subhazard ratio). The trial’s key secondary enpoint was clinically relevant bleeding, as assessed in a superiority evaluation.

Over a median treatment duration of 11.8 months (interquartile range, 8.3 to 12.1), recurrent venous thromboembolism was observed in 18 patients (cumulative incidence, 2.1%) in the reduced-dose cohort compared to 24 patients (cumulative incidence, 2.8%) in the full-dose cohort (adjusted subhazard ratio, 0.76; 95% confidence interval [CI], 0.41 to 1.41; P=0.001 for noninferiority).

Clinically relevant bleeding was reported in 102 patients (cumulative incidence, 12.1%) in the reduced-dose cohort compared to 136 patients (cumulative incidence, 15.6%) in the full-dose cohort (adjusted subhazard ratio, 0.75; 95% CI, 0.58 to 0.97; P=0.03). Mortality rates were 17.7% in the reduced-dose cohort compared to 19.6% in the full-dose cohort (adjusted hazard ratio, 0.96; 95% CI, 0.86 to 1.06).

“Extended anticoagulant therapy with reduced-dose apixaban was noninferior to full-dose apixaban with regard to the prevention of recurrent venous thromboembolism in patients with active cancer,” the study authors concluded. “Moreover, the reduced dose resulted in a lower incidence of clinically relevant bleeding than the full dose.”¹

References

1. Mahé I., et al. Extended Reduced-Dose Apixaban for Cancer-Associated Venous Thromboembolism. N Engl J Med 2025. Published March 29, 2025. DOI: 10.1056/NEJMoa2416112.

2. API-CAT STUDY for APIxaban Cancer Associated Thrombosis (API-CAT). ClinicalTrials.gov. Updated March 25, 2025. Accessed April 1, 2025. https://clinicaltrials.gov/study/NCT03692065

3. Agrawal A, Kerndt CC, Manna B. Apixaban. Updated February 22, 2024. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from https://www.ncbi.nlm.nih.gov/books/NBK507910/