In a novel comparison of direct oral anticoagulants for treating cancer-associated venous thromboembolism (VTE), rivaroxaban, apixaban, and enoxaparin demonstrated similar rates of VTE recurrence and bleeding. Results from the study were published in the American Journal of Hematology.

Researchers enrolled 750 patients who were diagnosed with cancer-associated VTE and started treatment with rivaroxaban, apixaban, or enoxaparin within 2 weeks of diagnosis. In total, 224 patients received apixaban, 163 patients received rivaroxaban, and 363 patients received enoxaparin.

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The primary efficacy end point was VTE recurrence. The primary safety end point was major bleeding. Clinically relevant nonmajor bleeding was a secondary safety end point, and a composite of major and clinically relevant nonmajor bleeding comprised a third safety end point.

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VTE recurred in 11 patients receiving apixaban, 7 patients receiving rivaroxaban, and 17 patients receiving enoxaparin. The hazard ratios (HR) for apixaban compared with rivaroxaban, apixaban compared with enoxaparin, and rivaroxaban compared with enoxaparin were 1.31 (P =.57), 1.14 (P =.74), and 0.85 (P =.73), respectively. These similarities held after 3 months and 6 months of follow-up.

There were 82 deaths in the apixaban group, 74 deaths in the rivaroxaban group, and 171 deaths in the enoxaparin group, yielding mortality rates of 55.7, 39.31, and 53.80 per 100 person-years, respectively. Mortality was lower in patients who received rivaroxaban compared with patients treated with both apixaban (P =.002) and enoxaparin (P =.03). At 6 months of follow-up, rivaroxaban continued to demonstrate lower mortality compared with apixaban (14.7% vs 36.6%; P =.01) and enoxaparin (14.7% vs 28.1%; P =.003).

Major bleeding occurred in 11 patients treated with apixaban, 12 patients treated with rivaroxaban, and 21 patients treated with enoxaparin. These rates of major bleeding were not statistically different. Rivaroxaban was associated with increased rates of clinically relevant nonmajor bleeding compared with both apixaban (HR, 0.31; P =.03) and enoxaparin (HR, 2.84; P =.01).

The authors noted that patient and medication selection bias could have influenced these results, and that further research is needed to confirm the lower mortality rates demonstrated with rivaroxaban in this study.


1. Wysokinski WE, Houghton DE, Casanegra NI, et al. Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism [published online August 4, 2019]. Am J Hematol. doi:10.1002/ajh.25604