In the API-CAT trial—results of which were reported in The New England Journal of Medicine—Mahé et al found that use of reduced-dose apixaban was noninferior to full-dose apixaban in preventing recurrent venous thromboembolism (VTE) in patients with active cancer.
Study Details
In the double-blind noninferiority trial, 1,766 patients from sites in 11 countries were randomly assigned between October 2018 and September 2023 to receive either 2.5 mg of apixaban twice daily (reduced-dose group, n = 866) or 5.0 mg of apixaban twice daily (full-dose group, n = 900) for 12 months. Patients had active cancer with prior proximal deep vein thrombosis or pulmonary embolism and had completed at least 6 months of anticoagulant therapy. Random assignment occurred at a median time since the index event of 8.0 months (interquartile range [IQR] = 6.5–12.6 months). The primary outcome measure of the study was fatal or nonfatal recurrent VTE on blinded central adjudication; the noninferiority margin was 2.00 for the upper bound of the 95% confidence interval (CI) of the subhazard ratio; the key secondary outcome measure was clinically relevant bleeding, assessed in a superiority analysis.
Key Findings
Median treatment duration among all patients was 11.8 months (IQR = 8.3–12.1 months).
Recurrent VTE occurred in 18 patients (cumulative incidence = 2.1%) in the reduced-dose group and in 24 patients (cumulative incidence = 2.8%) in the full-dose group (adjusted subhazard ratio = 0.76, 95% CI = 0.41–1.41, P = .001 for noninferiority).
Clinically relevant bleeding occurred in 102 patients (cumulative incidence = 12.1%) in the reduced-dose group and in 136 patients (cumulative incidence = 15.6%) in the full-dose group (adjusted subhazard ratio = 0.75. 95% CI = 0.58–0.97, P = .03).
Mortality at 12 months was 17.7% in the reduced-dose group and 19.6% in the full-dose group (adjusted hazard ratio = 0.96, 95% CI = 0.86–1.06). More than 80% of deaths in each group were due to cancer. Unexplained sudden death in which pulmonary embolism could not be ruled out was observed in three patients in the reduced-dose group and two patients in the full-dose group; however, no objectively confirmed cases of fatal pulmonary embolism were observed.
The investigators concluded, “Extended anticoagulation with reduced-dose apixaban was noninferior to full-dose apixaban for the prevention of recurrent [VTE] in patients with active cancer. The reduced dose led to a lower incidence of clinically relevant bleeding complications than the full dose.”
Isabelle Mahé, MD, PhD, of Hopital Louis Mourier, Service de Medecine Interne, Assistance Publique–Hopitaux de Paris, Universite Paris Cite, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the Bristol Myers Squibb–Pfizer Alliance. For full disclosures of the study authors, visit nejm.org.
