Trends and outcomes of direct oral anticoagulant use in patients with cancer: a nationwide cohort study

Background
Cancer-associated thrombosis (CAT) is increasingly acknowledged as one of the leading causes of death in patients with cancer. The 2022 European guidelines issued a level 1A recommendation for both direct oral anticoagulants (DOACs) and low-molecular-weight heparins (LMWH). However, while randomized trials support DOACs as an alternative to LMWH, their real-world implementation is still unclear.

Purpose
We investigated temporal trends in DOAC use for CAT according to cancer status, alongside factors associated with DOAC initiation, and associated risk of bleeding and re-thrombosis.

Methods
Using nationwide Danish registers, we included all patients with first-time venous thromboembolism (VTE) from 2012–2021. Cancer status was categorized as no cancer, history of cancer, non-active cancer or active cancer; restricted to either breast-, gastrointestinal- or lung cancer. Outcomes were 90-day probability of DOAC initiation, 1-year absolute risk (AR) of bleeding and re-thrombosis estimated using the Aalen-Johansen non-parametric method to account for competing risk of death. Factors associated with DOAC initiation were estimated using Cox regression models.

Results
A total of 45,887 patients diagnosed with a first-time VTE were identified (median age 69 years [56, 79]). The prevalence of comorbidities was largely unchanged throughout the study period. The 90-day probability of DOAC initiation for no cancer increased from 22.0% (95% CI: 21.2-22.8) in 2012-2014 to 69.2% (95% CI: 68.5-69.9) in 2018-2021. For active cancer, the 90-day probability increased from 3.2% (95% CI: 2.1-4.2) in 2012-2014 to 21.1% (95% CI: 19.0-23.1) in 2018-2021 (Figure 1). A lower hazard ratio (HR) for DOAC initiation was observed in patients with a history of cancer (0.86 [95% CI 0.80-0.93]), non-active cancer (0.45 [95% CI 0.43-0.48]), and diabetes (0.85 [95% CI 0.81-0.89]). The 1-year AR of bleeding in patients on DOAC decreased for patients without cancer, remained stable for those with a history of cancer, increased for those with non-active cancer and decreased for patients with active cancer throughout the study period (Table 1). Conversely, the 1-year AR of re-thrombosis increased for patients without cancer, remained stable for those with history of cancer, increased for those with non-active cancer and active cancer (Table 1).

Conclusions
In a nationwide VTE cohort, DOAC use increased from 2012-2021 but remained low in patients with active cancer (21%). The increased use of DOAC was not associated with higher bleeding rates, supporting DOAC safety. Findings align with current guideline recommendations, reinforcing their implementation in real-world CAT patients.