Apixaban for the treatment of recurrent cancer-associated VTE

By Jeff Shenfeld, PGY-3

Venous thromboembolism (VTE) has been found to be a common cause of morbidity and mortality in patients with cancer. Patients with cancer are at risk of both recurrent thromboembolism and bleeding, making the challenge anticoagulation a difficult one. Current guidelines recommend the use of low-molecular-weight heparin for the treatment of cancer-associated VTE, and recently, oral agents such as edoxaban and rivoroxaban have been added. However, these oral agents have been found to be associated with higher risks of bleeding, especially in the gastrointestinal tract. The Carvaggio trial was done to assess whether oral apixaban would be noninferior to subcutaneous dalteparin, a low-molecular-weight heparin for the prevention of recurrent VTE in cancer patients without increasing the risk of major bleeding.

The trial was multinational, randomized, and controlled. The primary outcome was recurrent VTE, which occurred in 5.6% of the apixaban group, and 7.9% of the dalteparin group. Major bleeding occurred in 3.8% of the apixaban group, and 4.0% of the dalteparin group. Major GI bleeding occurred in 1.9% of the apixaban group, and 1.7% of the dalteparin group. Major non-GI bleeding occurred in 1.9% of the apixaban group, and .2% of the dalteparin group. There were no fatal bleeding episodes in the apixaban group, and 2 in the dalteparin group. 

This trial found oral apixaban to be noninferior to subcutaneous dalteparin for the treatment of recurrent VTE in patients with cancer. This is consistent with and further contributes to the evidence of the efficacy of direct oral anticoagulants in the treatment of VTE in cancer patients. Apixaban was found to be associated with similar rates of major bleeding. This included major gastrointestinal bleeding, which contrasted with previous studies of other direct oral anticoagulants, which showed higher incidences of GI bleeding.

There were several trial limitations. These include the trial being open-label, GI bleeding was not a prespecified trial outcome, and that patients with certain cancers, including brain tumors, known cerebral metastases, or acute leukemia were excluded for safety reasons. However, despite these limitations, apixaban was found to have a favorable safety profile that is consistent with the results of previous randomized control trials. Moving forward, the use of apixaban may be expanded to patients with both cancer and venous thromboembolism without incurring an increased risk of major bleeding.

Agnelli, Giancarlo, et al. “Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer.” New England Journal of Medicine, vol. 382, no. 17, 2020, pp. 1599–1607., doi:10.1056/nejmoa1915103.