Reduced-dose apixaban noninferior to full dose for cancer-associated thrombosis

1. Among patients with active cancer and prior venous thromboembolism (VTE), extended treatment with reduced-dose apixaban demonstrated noninferior efficacy to full-dose apixaban in preventing recurrent VTE during a 12-month follow-up period.

2. The incidence of clinically relevant bleeding was significantly lower in the reduced-dose group, suggesting an improved safety profile without compromising therapeutic effectiveness.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Though direct oral anticoagulants are indicated for the treatment of VTE, there are risks associated with their use. Malignancy increases the risk of VTE, and therefore, medications like apixaban are more commonly used in this population. This randomized, double-blind, noninferiority trial evaluated the efficacy and safety of extended anticoagulation with reduced-dose versus full-dose apixaban in patients with active cancer and a history of proximal deep-vein thrombosis or pulmonary embolism. Following at least six months of prior anticoagulant therapy, 1,766 patients were randomized and followed for an additional 12 months. Reduced-dose apixaban was noninferior to full-dose in preventing recurrent VTE and was associated with a lower incidence of clinically relevant bleeding. These findings support the consideration of dose reduction for extended anticoagulation in this high-risk population. Strengths include rigorous methodology, international multicenter design, and independent outcome adjudication. Limitations include the lack of long-term follow-up beyond 12 months and the absence of race/ethnicity data due to regulatory constraints.

Click to read the study in NEJM

Relevant Reading: Apixaban for Extended Treatment of Venous Thromboembolism

In-Depth [randomized controlled trial]: This randomized, double-blind, noninferiority trial (API-CAT) investigated whether a reduced dose of apixaban (2.5mg twice daily) is as effective and safer than the standard full dose (5.0 mg twice daily) for extended anticoagulation in patients with cancer-associated VTE. The trial enrolled 1,766 patients across 121 centers in 11 countries. All patients had active cancer and a confirmed history of proximal deep-vein thrombosis or pulmonary embolism, and had completed at least six months of initial anticoagulant therapy. Participants were randomized 1:1 to receive either reduced- or full-dose apixaban for an additional 12 months, with central adjudication of outcomes and stratification by cancer type and initial VTE event. The primary outcome was recurrent, fatal, or nonfatal VTE. This occurred in 18 patients (2.1%) in the reduced-dose group and 24 (2.8%) in the full-dose group (adjusted subhazard ratio, 0.76; 95% CI, 0.41–1.41), meeting the prespecified noninferiority margin (2.00). The key secondary safety outcome was clinically relevant bleeding, which occurred in 102 patients (12.1%) in the reduced-dose group compared to 136 (15.6%) in the full-dose group (adjusted subhazard ratio, 0.75; 95% CI, 0.58–0.97; P=0.03). Major bleeding occurred in 2.9% and 4.3% of patients, respectively. Subgroup analyses showed consistent findings across cancer types and performance status categories. Mortality rates were comparable between groups (17.7% vs. 19.6%), with most deaths attributed to cancer. The study concluded that reduced-dose apixaban offers a favorable balance between efficacy and bleeding risk for extended anticoagulation in cancer patients beyond the initial six-month treatment period.

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