Direct Oral Anticoagulant Therapy in Cancer

Direct Oral Anticoagulant Therapy in Cancer
Sara Massey, PharmD, MOBE 

Background: Patients diagnosed with different types of cancer are at an increased risk of thrombosis as well as an increased risk of bleeding. Currently, low-molecular-weight heparin (LMWH) is the standard treatment to prevent venous thromboembolisms (VTE) in patients with cancer, which was determined in the early 2000’s by the CLOT trial (LMWH compared to vitamin k antagonist). Since then, direct oral anticoagulants (DOAC) have been introduced and have many advantages including fewer food and drug interactions and more predictable pharmacodynamics and pharmacokinetics. This study aimed to compare the safety and efficacy of DOACs and LMWH in cancer-associated VTE. 

Evidence: This study was a retrospective analysis in an academic teaching hospital.  Patients included were aged 18 to 89 years old with active cancer being treated with a DOAC or LMWH for VTE. Patients were excluded if there was a documented history of atrial fibrillation, vascular disease, weight >120 kg or body mass index >40 kg/m2, hypercoagulable disorder, pregnancy, severe renal impairment, hepatic impairment, or concomitant use of a strong CYP-450 3A4 or P-glycoprotein inhibitor/inducer. The primary outcome of this study was the frequency of VTE reoccurrence in each patient. There were multiple secondary outcomes including major and minor bleeding events and occurrence of other thrombosis. 

Of the 456 patients identified for the study, 156 patients were included in the study population. All patients were prescribed the manufacturer recommended dose of a DOAC or LMWH. Both the DOAC and LMWH groups contained an equal number of patients (n=78). In the DOAC group, 76% of the patients were on rivaroxaban, 18% on apixaban, and 6% on dabigatran. All patients in the LMWH group were on enoxaparin. The primary outcome of VTE occurred in 5 patients in the DOAC group and in 8 patients in the LMWH group, 6.4% and 10.3% respectively, (0.6 [95% CI 0.19 - 1.92]). The secondary outcome of major bleeding (0.49 [95% CI 0.9 - 2.74]) and minor bleeding (1.32 [95% CI 0.47 - 3.75]) were similar when comparing the DOAC group to the LMWH group.  

Discussion: The investigators described this study as one of the first to compare DOACs to LMWH in patients with cancer in a real-life setting. There are some limitations including a single-center chart review, lack of patient adherence tracking, potential bleeding or VTE recorded at a different institution, difference in the length of follow-up between and within groups, and difference of metastatic disease between groups. With the few limitations and size of the study,additional studies evaluating the safety and efficacy of using DOACs for VTE prevention in patients with cancer are warranted. 

Clinical Impact: This study showed a similar occurrence of VTE when using DOACs and LMWH in patients with cancer. With a similar VTE and bleeding frequency, this potentiates the use of DOACs as an alternative for VTE prevention in cancer patients. The use of DOACs will allow patients an oral agent option, with less follow-up required, and fewer drug and food interactions.  

References: 

  1. Fovel L, Seabury R, Miller C, et al. Safety and Efficacy of Direct Oral Anticoagulants in Patients with Cancer. J Pharm Prac. 2019. doi:10.1177/0897190019896500. [ePub ahead of print].