SUMMARY: The Center for Disease Control and Prevention (CDC) estimates that approximately 1-2 per 1000 individuals develop Deep Vein Thrombosis (DVT)/Pulmonary Embolism (PE) each year in the United States, resulting in 60,000-100,000 deaths. Venous ThromboEmbolism (VTE) is the third leading cause of cardiovascular mortality, after myocardial infarction and stroke. Ambulatory cancer patients initiating chemotherapy are at varying risk for Venous Thromboembolism (VTE), which in turn can have a substantial effect on health care costs, with negative impact on quality of life.
Approximately 20% of cancer patients develop VTE and about 20% of all VTE cases occur in patients with cancer. There is a two-fold increase in the risk of recurrent thrombosis in patients with cancer, compared with those without cancer, and patients with cancer and VTE are at a markedly increased risk for morbidity and mortality. The high risk of recurrent VTE, as well as bleeding in this patient group, makes anticoagulant treatment challenging. Traditionally, a six-month course of either Direct Oral AntiCoagulants (DOACs) or Low-Molecular-Weight Heparin (LMWH) has served as the standard initial treatment duration.
However, cancer is a chronic and often progressive condition, and the thrombotic risk doesn’t dissipate once the initial treatment window concludes. Clinical guidelines generally recommend the continuation of anticoagulation for as long as the malignancy remains active or systemic therapy is ongoing. Yet, this approach necessitates a careful balancing act – prolonged anticoagulation mitigates thrombotic recurrence but heightens the risk of bleeding, a risk that persists over time.
A major challenge in this domain has been the lack of robust evidence from randomized clinical trials to guide extended anticoagulation beyond six months, particularly regarding the optimal dose that maintains efficacy while minimizing harm. While reduced-dose anticoagulation has emerged as a promising strategy in non-cancer populations, its application to cancer-associated thrombosis had not been thoroughly evaluated until recently.
The Apixaban Cancer Associated Thrombosis (API-CAT) trial is a large, randomized, double-blind, noninferiority study aimed to determine whether a reduced dose of Apixaban (2.5 mg twice daily) could effectively prevent recurrent VTE in patients with active cancer, while also offering a safer bleeding profile, compared to the standard full dose (5 mg twice daily). All participants had previously completed a minimum of six months of anticoagulation for either proximal deep-vein thrombosis or pulmonary embolism. The trial enrolled 1,766 patients, randomly assigned to either the reduced-dose (N=866) or full-dose (N=900) Apixaban group. The baseline characteristics of the patients in this trial were similar to those in observational studies and randomized trials. The median age of the patients was 69 years, and 43% were men. Among patients with active cancer, the most frequent sites of the primary cancer were the breast (22.7%), colon or rectum (15.2%), gynecologic system (12.1%), and lung (11.3%). The Primary efficacy outcome was centrally adjudicated fatal or nonfatal recurrent VTE over the 12-month follow-up period and key Secondary outcome was clinically relevant bleeding, which was defined as a composite of adjudicated major or clinically relevant nonmajor bleeding during the 12-month follow-up period.
The results were compelling: the reduced-dose regimen demonstrated noninferiority to the full dose in preventing VTE recurrence. Specifically, recurrent events occurred in 2.1% of patients in the reduced-dose group compared to 2.8% in the full-dose group (adjusted subhazard ratio=0.76; P=0.001 for noninferiority). More importantly, the incidence of clinically relevant bleeding – a composite measure that included both major and non-major events with real-world impact – was significantly lower in the reduced-dose group (12.1% vs. 15.6%; adjusted subhazard ratio=0.75; P=0.03). The incidence of death was similar in the two groups (19.6% in the full-dose group and 17.7% in the reduced-dose group), and most deaths were related to cancer.
Notably, the study defined clinically relevant bleeding more broadly than previous trials—capturing both major and non-major events that impact patient well-being and quality of life. This approach reflects the reality that even so-called “minor” bleeds can significantly affect daily functioning and emotional health, particularly in patients with incurable malignancies.
In conclusion, reduced-dose Apixaban offers a clinically effective and safer alternative for extended anticoagulation in patients with active cancer, successfully preventing recurrent venous thromboembolism while minimizing bleeding risks. With cancer patients living longer due to advances in immunotherapy and targeted treatments, clinicians are increasingly tasked with navigating long-term thrombosis prevention strategies. The API-CAT trial helps address a key evidence gap and marks a significant advancement in the long-term management of cancer-associated thrombosis and reinforces the importance of personalized care in oncology.
Cancer-Associated Venous Thromboembolism- Beyond 6 Months. Mahe I, Carrier M, Mayeur D, et al. for the API-CAT Investigators. N Engl J Med 2025;392:1439-1440
