Direct Oral Anticoagulants Versus LMWH in Preventing Recurrent VTE in Cancer

At the 2021 ASCO Annual Meeting, two posters reported results from the CANVAS trial, which described the risk-benefit profiles of direct oral anticoagulants (DOACs) and low-molecular-weight heparin (LMWH) to prevent recurrent venous thromboembolism (VTE) in patients with cancer.

Overall, DOACs were noninferior to LMWH in terms of recurrent VTE, with no differences in rates of bleeding or death between the anticoagulation strategies. However, patients who received DOACs reported higher rates of satisfaction with the treatment, likely due to the lower treatment burden. Deborah Schrag, MD, MPH, of Dana-Farber Cancer Institute, was the lead author on both posters.

“Previous randomized trials in cancer patients suggest that DOACs are noninferior to LMWH for preventing recurrent VTE but have higher risk of bleeding,” Dr. Schrag and colleagues noted. “However, the balance of benefits and burdens remains uncertain.”

The CANVAS pragmatic trial is an unblinded, hybrid comparative-effectiveness noninferiority trial, which enrolled a total of 638 patients with cancer and VTE into randomized and preference cohorts between December 2016 and April 2020. Participants had been diagnosed with any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

Participants were randomized 1:1 to receive either DOAC (n=330) or LMWH (n=308); if assigned to LMWH, transitions to warfarin were allowed.

The preference cohort consisted of 137 participants who declined randomization, chose their preferred anticoagulant, and were followed for six months; this cohort was closed when predetermined stopping criteria were met. A total of 107 patients selected DOACs and 30 patients selected LMWH.

In the first analysis, researchers compared rates of recurrent VTE, bleeding, and death between the DOAC and LMWH groups.1 The primary goal was to establish noninferiority of anticoagulation with a DOAC, as defined by the upper limit of the two-sided 90% confidence interval for the difference in the event rate at six months of less than 3%.

The researchers reported that, at the final follow-up on November 30, 2020, the noninferiority criteria for recurrent VTE were met (TABLE 1). In the combined cohort, rates of recurrent VTE were 6.4% with DOACs and 7.8% with LMWH, for a difference of 1.3%. There also were no significant differences regarding secondary endpoints in this cohort: Rates of major bleeding were 5.4% and 4.4% with DOACs and LMWH, and rates of death were 20.5% and 19.3%, with DOACs and LMWH, respectively.

In the second analysis, Dr. Schrag and researchers examined patients’ perspectives on LMWH versus DOACs for preventing recurrent VTE, including the impact on health-related quality of life (QOL), treatment satisfaction, and perceptions of benefit and burden.2

For this study, participants reported QOL at baseline, three, and six months by completing the 12-Item Short Form Survey. At three and six months, they also reported satisfaction via the Anti-Clot Treatment Scale (ACTS), which includes a burden and a benefit scale. A two-point change was prespecified as significant.

There were no differences in QOL or patients’ perceptions of treatment benefits between groups, the authors reported. However, “patients who received DOACs reported lower treatment burden compared to those assigned to LMWH therapy,” they added (TABLE 2). This likely stemmed from decreased perception of the treatment of burden with the oral therapy.

Overall, the results suggest that DOACs are noninferior to LMWH in terms of preventing recurrent VTE in this population, with an advantage in terms of patient-reported outcomes. However, the findings are limited by the unblinded design of the trial, which may have introduced bias.

The authors report no relevant conflicts of interest.


  1. Schrag D, Uno H, Zattra O, et al. Patient-reported benefits and burdens of direct oral-anticoagulants (DOACs) and low molecular weight heparins (LMWHs): The CANVAS pragmatic randomized trial (AFT-28). Abstract #12112. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.
  2. Schrag D, Uno H, Rosovsky RPG, et al. The comparative effectiveness of direct oral anti-coagulants and low molecular weight heparins for prevention of recurrent venous thromboembolism in cancer: The CANVAS pragmatic randomized trial. Abstract #12020. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.