Direct Oral Anticoagulants Show Superiority to Low Molecular Weight Heparin for Venous Thromboembolism

Direct oral anticoagulants (DOACs) have been associated with higher persistence rates, lower risks of venous thromboembolism (VTE) recurrence, lower risk of major bleeding, and improved mortality, according to the results of a study published in JAMA Network Open. Investigators also said that warfarin could still be considered for individuals with contraindications to DOACs and those with poor persistence on low-molecular weight heparin.

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“DOACs have emerged as the most prescribed anticoagulant choice for management of cancer-associated VTE,” the investigators wrote.

The authors of the study said that the efficacy and clinical utilization of anticoagulants for cancer-associated thrombosis have rarely been investigated. The study aimed to determine the patterns and associated risk factors with anticoagulant usage, evaluating the efficacy of these drugs in individuals with active cancer in the clinical setting.

Data were obtained from the OptumLabs electronic health record claims from January 1, 2012, to September 30, 2019. Individuals aged 18 years or older were included if they had a primary cancer diagnosis, excluding skin cancer, during at least 1 inpatient or 2 outpatient visits within 6 months prior to VTE. Investigators analyzed the data from April 2020 to September 2021.

Investigators grouped individuals according to the anticoagulant that was prescribed, including DOACs, low-molecular weight heparin, and warfarin. They used odds ratios to determine associations between risk factors and the utilization of anticoagulants. The study authors noted that the risk of VTE recurrence and all-cause mortality were the main efficacy outcomes, while the mean safety outcomes included the risk of hospitalization due to major bleeding.

There were 5100 individuals included in the study, with the majority being women and White, with a mean age of 66.3 years. Investigators reported that 49.3% filled prescriptions with DOACs, 29.2% with low-molecular weight heparin, and 28.6% with warfarin. The median treatment duration was 3.2, 1.8, and 3.1 months, respectively.

Individuals with lung, urological, gynecological, and colorectal cancers were associated with an increase of low-molecular weight heparin prescriptions when compared with DOACs. Younger individuals were also more likely to be prescribed low-molecular weight heparin.

Low-molecular weight heparin and warfarin were associated with an increased risk of VTE recurrence at 39.76 per 100 person-years and 29.89 per 100 person-years, respectively, compared with 20.62 person-years for DOACs. Additionally, those who received low-molecular weight heparin had an increased risk of all-cause mortality at 21.18 per 100 person-years compared to 11.36 per 100 person-years for DOACs. There were no significant differences in mortality rates for warfarin and DOACs.

Further, low-molecular weight heparin was also associated with an increased risk of hospitalizations due to major bleeding compared to DOACs at 26.73 per 100 person-years and 9.88 per 100 person-years, respectively. The study authors noted that many of these events were from gastrointestinal (GI) bleeding associated with low-molecular weight heparin compared with DOACs, but major genitourinary bleeding events were low. There was an increased risk of intracranial bleeding with low-molecular weight heparin compared to DOACs.

For warfarin, investigators reported that the rates of major bleeding, GI bleeding, and intracranial bleeding were similar to DOACs. There were no significant differences among the drugs for GI bleeding in the upper GI malignant neoplasm, according to the post hoc sensitivity analysis.

Investigators said that DOACs and warfarin could offer better treatment compared to low-molecular weight heparin, evident in the results of the study.

Reference

Riaz IB, Fuentes H, Deng Y, Naqvi SAA, et al. Comparative effectiveness of anticoagulants in patients with cancer-associated thrombosis. JAMA Netw Open. 2023;6(7):e2325283. doi:10.1001/jamanetworkopen.2023.25283