Extended Reduced-Dose Apixaban for Treatment of VTE in Cancer Patients
CLINICAL QUESTION: Following full-dose treatment for six months, is reduced-dose apixaban noninferior to full-dose apixaban for the prevention of further recurrence of venous thromboembolism (VTE) in cancer patients?
BACKGROUND: For cancer patients with VTE, current guidelines recommend six months of full-dose anticoagulation followed by continuous anticoagulation while the cancer is active or therapy is ongoing. However, anticoagulation has a significant risk of bleeding, particularly when needed for long-term or indefinite treatment duration. Optimal treatment regimen after the initial six months is unclear.
STUDY DESIGN: Randomized, double-blinded, noninferiority trial
SETTING: Large international trial (121 centers, 11 countries)
SYNOPSIS: After six months of full-dose anticoagulation following an initial VTE, 1,766 patients with active cancer were randomized to full-dose apixaban (5 mg twice daily) versus reduced-dose apixaban (2.5 mg twice daily). During a median follow-up time of 11.8 months, recurrent VTE occurred in 2.1% of the reduced-dose group versus 2.8% of the full-dose group (adjusted subhazard ratio, 0.76; 95% confidence interval [CI], 0.41 to 1.41, P = 0.001 for noninferiority), demonstrating that reduced-dose apixaban was noninferior for the prevention of VTE. The secondary outcome of major or clinically relevant bleeding was significantly lower in the reduced-dose apixaban group (adjusted subhazard ratio, 0.75; 95% CI, 0.58 to 0.97; P = 0.03).
Trial patients likely had better performance status and fewer comorbidities than hospitalized cancer patients. 92.6% of patients had Eastern Cooperative Oncology Group performance status of 0 to 1 and the trial excluded patients with primary brain tumors, intracranial metastases, abnormal liver tests, platelets under 75,000, and creatinine clearance under 30. Hospitalists should consider that their patients may have a higher risk of VTE recurrence and significant bleeding than the study population.
BOTTOM LINE: Reduced-dose apixaban is non-inferior compared to full-dose apixaban for the prevention of recurrent VTE in cancer patients and has a significantly lower risk of bleeding.
CITATION: Mahé I, et al. Extended reduced-dose apixaban for cancer-associated venous thromboembolism. N Engl J Med. 2025;392:1363-1373. doi: 10.1056/NEJMoa2416112.
Dr. Johnson
Dr. Johnson is an assistant clinical professor and a hospitalist at UC San Diego Health in San Diego.