API-CAT Findings Support Existing NCCN Cancer-Associated VTE Guidance

Patients with cancer are predisposed to recurrent venous thromboembolism (VTE) because malignancy creates a hypercoagulable state, 1 of the 3 components of Virchow’s triad (Figure 1).¹ The consideration for VTE prophylaxis in malignancy should be guided by an individualized assessment of both thrombosis risk and major bleeding risk, weighing potential benefits against harms.²

For recurrent cancer-associated VTE (CAT), the American Society of Hematology (ASH), National Comprehensive Cancer Network (NCCN), and American Society of Clinical Oncology (ASCO) clinical practice guidelines recommend either a direct oral anticoagulant (DOAC) or low-molecular-weight heparin (LMWH).^2-4 Guideline-supported DOACs include apixaban (Eliquis; Bristol Myers Squibb), rivaroxaban (Xarelto; Johnson & Johnson), and edoxaban (Savaysa; Daiichi-Sankyo), all of which directly inhibit factor Xa, preventing fibrin clot formation.^2-5

Anticoagulation is generally continued for at least 6 months and can be continued for as long as the cancer remains active or the patient is receiving anticancer treatment.^2-4 Additionally, the NCCN guidelines recommend reduced-dose DOACs, such as apixaban 2.5 mg twice daily, in ambulatory patients with cancer with intermediate-to-high risk for VTE determined by a Khorana score of 2 or greater (Table 1^3,7).³ This recommendation is based on findings from the Apixaban for the Prevention of Venous Thromboembolism in the High-Risk Ambulatory Cancer Patients (AVERT) trial.⁶

In the double-blind, randomized, noninferiority API-CAT trial, 866 patients were assigned to receive apixaban 2.5 mg twice daily (reduced dose), and 900 patients were assigned to receive apixaban 5 mg twice daily (full dose). Eligible participants had active cancer with a history of VTE, had completed at least 6 months of anticoagulation for CAT, and continued treatment for an additional 12 months as secondary prophylaxis.⁸

The primary objective was to determine whether reduced-dose apixaban was noninferior to the full dose for preventing recurrent CAT. Patients in the reduced-dose apixaban group had a 24% lower risk of the primary outcome and a 25% lower risk of clinically relevant bleeding compared with full-dose apixaban. However, mortality rates were similar between both groups.⁸

These results support the use of reduced-dose apixaban for extended prophylaxis in patients with active cancer, a recommendation already included in the NCCN guidelines prior to this trial.⁸

The key takeaway is that clinicians can maintain efficacy while reducing bleeding risk by stepping down to reduced-dose apixaban after 6 months of initial therapy, potentially improving patient comfort and adherence. As always, anticoagulation decisions in cancer care should be individualized through ongoing discussion of risks, benefits, and patient preferences.

REFERENCES

1. Donnellan E, Khorana AA. Cancer and venous thromboembolic disease: a review. Oncologist. 2017;22(2):199-207. doi:10.1634/theoncologist.2016-0214

2. Lyman GH, Carrier M, Ay C, et al. American Society of Hematologist 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv. 2021;5(4):927-974. doi:10.1182/bloodadvances.2020003442

3. NCCN. Clinical Practice Guidelines in Oncology. Cancer-Associated Venous Thromboembolic Disease, Version 2.2025. Accessed August 28, 2025. https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf

4. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496-520. doi:10.1200/JCO.19.01461

5. Eliquis [prescribing information]. Bristol Myers Squibb; May 2025. Accessed September 3, 2025. https://packageinserts.bms.com/pi/pi_eliquis.pdf

6. Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2019;380(8):711-719. doi:10.1056/NEJMoa1814468

7. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902-4907. doi:10.1182/blood-2007-10-116327

8. Mahé I, Carrier M, Mayeur D, et al. Extended reduced-dose apixaban for cancer-associated venous thromboembolism. N Engl J Med. 2025;392(14):1363-1373. doi:10.1056/NEJMoa2416112