Current guidelines recommend at least 6 months of full-dose anticoagulation with a low-molecular-weight heparin or a direct oral anticoagulant for the initial treatment of cancer-associated venous thromboembolism (VTE) and suggest extending anticoagulation treatment beyond 6 months in patients with active cancer or who are still receiving systemic cancer therapy, unless they are at high bleeding risk. Nevertheless, the optimal intensity of extended anticoagulation beyond 6 months remains unclear.

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of reduced-dose vs full-dose apixaban for the extended treatment of cancer-associated VTE.

A literature search of PubMed, Embase, and Cochrane Library was performed up to August 2025 to identify randomized controlled trials (RCTs) comparing reduced-dose vs full-dose apixaban for extended treatment of cancer-associated VTE. Risk ratios (RR) and 95% CIs were estimated using a fixed-effects model. The primary outcome was the net clinical benefit (NCB), defined as recurrent VTE or clinically relevant bleeding (CRB, i.e., composite of major or clinically relevant non-major bleeding). The secondary outcomes included recurrent VTE, CRB, and all-cause mortality.

Two RCTs involving 2126 patients were included in the meta-analysis. The mean age of patients was 68 ± 10 years, and the duration of follow-up was 12 months. Reduced-dose apixaban significantly improved the NCB (RR, 0.79; 95% CI, 0.65–0.96). Reduced-doses apixaban were comparable with full-dose apixaban in preventing recurrent VTE (RR, 0.87; 95% CI, 0.53–1.44) and all-cause mortality (RR, 0.94; 95% CI, 0.78–1.14). However, reduced-dose apixaban significantly reduced the risk of CRB (RR, 0.77; 95% CI, 0.62–0.97) compared with full-dose apixaban.

The most striking finding of this study is the significant 23% relative reduction in CRB with the reduced-dose regimen (11.3% vs 14.6%). These results could translate into reduced morbidity, fewer transfusions and hospitalisations, decreased healthcare costs, and an improved quality of life for patients.

Reduced-dose apixaban improved the NCB during extended anticoagulation for cancer-associated VTE compared with full-dose apixaban and were associated with significantly lower bleeding risks. Longer-term follow-up real-world studies are needed to assess the durability of these findings.