Clinical question: Are direct oral anticoagulants (DOACs) acceptable compared to low-molecular-weight heparin (LMWH) for preventing venous thromboembolism (VTE) with a safe bleeding risk in cancer patients?
Background: LMWH has long been the standard of care in cancer patients with VTE and for future VTE prevention. Are DOACs now a viable option?
Study design: Randomized clinical trial
Setting: 67 U.S. member centers of the Alliance for Clinical Trials in Oncology research network
Synopsis: 671 participants were randomized to either the DOAC or LMWH group. Rates of VTE were 6.1% in the DOAC group and 8.8% in the LMWH group, consistent with a non-inferior outcome. Major bleeding occurred in 5.2% of the DOAC group and 5.6% of the LMWH group, also showing DOACs to be non-inferior. Severe adverse events (anemia, death) occurred in 33.8% of the DOAC group and 35.1% of the LMWH group. The study included a wide range of disease states, including numerous types of cancer, the presence of metastatic disease, impaired performance status, and reduced hepatic and renal function. This likely broadens the application of its result. Conversely, its low proportional recruitment of Asian, Hispanic, and Black individuals may limit its generalizability in those populations. Additionally, around 10% fewer participants were “taking [the medication] as prescribed” at three and six months in the LMWH group. This may reflect reduced adherence with injectable medications, as physicians might anticipate, though it could also lead to an underestimate of both the benefit and the side-effect profile from LMWH medications.
Bottom line: In adult patients with active cancer and VTE, DOACs are non-inferior to LMWH for preventing VTE over a six-month follow-up period. The most common serious events of anemia and death occurred similarly in both groups.
Citation: Schrag D, et al. Direct oral anticoagulants vs low-molecular-weight heparin and recurrent VTE in patients with cancer. JAMA. 2023;329(22):1924-33.
Dr. McKnight
Dr. Emery
Drs. McKnight and Emery are clinical assistant professors in the department of hospital medicine at The Ohio State University Wexner Medical Center in Columbus, Ohio.