Open Issues in the Choice and Management of Direct Oral Anticoagulants in Patients with Cancer-Related Venous Thromboembolism

Edoxaban, Rivaroxaban, or Apixaban for Cancer-Associated Venous Thromboembolism in the Real World: Insights from the COMMAND VTE Registry-2

In this issue of the Journal, Sueta and co-authors[1] report a sub-analysis from the COMMAND VTE Registry 2 regarding the safety and efficacy of direct oral anticoagulants (DOACs) in patients with cancer-associated venous thromboembolism (VTE). The study included 1,197 patients with active cancer treated with edoxaban (n = 643, 54%), rivaroxaban (n = 297, 25%), and apixaban (n = 257, 22%). Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. Regarding bleeding events, the 5-year incidence of major and clinically relevant bleeding was lower in the rivaroxaban group than with other DOACs (22.6, 14.0, and 22.8%, p = 0.04; and 37.6, 26.8, and 38.3%, p = 0.01, respectively). This result was mitigated by adjustment for confounders.

Edoxaban was the most commonly used DOAC in the overall cohort, followed by rivaroxaban and apixaban. Characteristics of patients varied according to the DOAC used ([Table 1]). Indeed, patients on edoxaban were more frequently women, with anemia, terminal cancer, and with isolated distal deep vein thrombosis (DVT), while in the rivaroxaban group there was the lowest proportion of women, terminal cancer, and anemia. Patients on apixaban were more likely to have pulmonary embolism with or without DVT and to be treated with thrombolysis ([Table 1]).

Table 1 Summary of clinical characteristics of treatment groups in the study by Sueta et al[1]

Edoxaban	Rivaroxaban	Apixaban
↑ Women	↓ Women	↑ Thrombolysis
↑ Terminal cancer	↓ Terminal cancer	↑ PE with or without DVT
↑ Anemia	↓ Anemia
↓ PE/↑ DVT only
↓ Thrombolysis

Abbreviations: DVT, deep vein thrombosis; PE, pulmonary embolism.

The study deals with an important clinical topic related to the management of VTE associated with active cancer[2] [3] that may be influenced by clinical characteristics, endovascular devices,[4] and concomitant therapies.[5] Indeed, the comparative effectiveness and safety of various treatment strategies for patients with cancer are a topic of great interest.[6] [7]

Patients included in the COMMAND VTE Registry 2 have different characteristics compared to randomized clinical trials. As an example, compared to the HOKUSAI VTE and CARAVAGGIO, there is a lower prevalence of metastatic disease but a higher rate of cardiovascular comorbidities.[8] [9] Of note, the population was largely Asian, and racial differences in the propensity to bleeding have been reported.[10] In addition, risk factors and biomarkers for cancer-related VTE and bleeding have some heterogeneity between different cohorts, although common risk factors do feature.[11] [12] [13]

Interestingly, the cancer site does not seem to influence the choice of DOAC. In 2019, the European Society of Cardiology guidelines suggested not to use edoxaban and rivaroxaban in patients with gastrointestinal cancer.[14] A similar remark has been given by the 2021 Second Update of the CHEST Guideline and Expert Panel Report on antithrombotic treatment for VTE.[15] In the study by Sueta et al, the proportion of colon cancer was similar in the three groups.

Regarding initial treatment strategy, nearly 40% of patients received parenteral anticoagulation also when DOACs with approved loading doses were chosen, and despite a similar safety and efficacy of DOACs compared to low-molecular-weight heparin.[16] [17]

Another interesting observation relates to the rate of discontinuation of DOAC therapy. This was 58% for rivaroxaban, 64.1% for edoxaban, and 62.8% for apixaban within 5 years. These results suggest that despite the availability of low-dose DOACs for long-term therapy, many patients interrupt anticoagulation after VTE-associated cancer. Reasons for discontinuation need to be explored. Early discontinuation of DOAC may lead to an increased risk of thrombosis, so worsening the prognosis of cancer patients, especially in some cancer types such as lung, brain, and pancreas.[18] [19]

In conclusion, the authors provide interesting real-world and long-term data on the use of DOACs in patients with cancer-associated VTE. Characteristics related to cancer do not seem to influence the choice of DOACs, while type of VTE and bleeding risk factors appear as important modulators of DOACs' choice ([Fig. 1]).

Fig. 1 Factors influencing the choice of DOACs for VTE treatment in cancer patients.

Publication History

Received: 24 July 2024

Accepted: 25 July 2024

Article published online:
06 August 2024

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