From Pages to Practice

By James Yeh, MD MPH

Published January 5, 2022


Patients with active cancer have a heightened risk of venous thromboembolism (VTE). Recently, I had a patient who presented to clinic with unilateral leg swelling and was subsequently found to have venous thromboembolus and pancreatic cancer. How would you manage this patient’s anticoagulation therapy?

The standard of care and guideline-endorsed treatment for patients with VTE and cancer is to use parenteral anticoagulation with low-molecular-weight heparin (LMWH)-based products over oral vitamin-K–based anticoagulants (VKAs), because LMWH-based products are associated with greater risk reduction than VKAs. However, the use of direct oral anticoagulants (DOACs) has increased during the past decade and may be preferred over VKAs and parenteral anticoagulants due to the ease of use. DOACs also have similar efficacy and reduced risk of bleeding as VKA for acute VTE in noncancer patients. 

Although the DOAC apixaban is approved for the treatment of acute VTE, limited data support the use of DOACs in patients with cancer. In a randomized, placebo-controlled trial published in NEJM, Carrier et al. examined the efficacy and safety of apixaban in patients with cancer and active VTE. The results suggest that apixaban is a viable anticoagulation option for patients with cancer as described above.

The following NEJM Journal Watchsummary explains the study.


Thromboprophylaxis with Apixaban for Cancer Patients

The American Society of Hematology 2018 guidelines for the prevention of venous thromboembolism (VTE) in patients with active malignancy recommend low-molecular-weight heparin (LMWH), or aspirin if LMWHs are not feasible (Blood Advances 2018; 2:3198). Whether direct oral anticoagulants (DOACs) would be safe and effective for this indication is unclear.

To address this issue, investigators conducted an industry-funded, randomized, placebo-controlled, double-blind trial of the direct factor Xa inhibitor apixaban (2.5 mg twice daily) in 574 ambulatory cancer patients with intermediate-to-high–risk malignancies. Apixaban or placebo was given within 24 hours of starting chemotherapy and continued for 6 months.

VTE was less frequent in patients assigned to apixaban versus placebo (4.2% vs. 10.2%; hazard ratio 0.41; P<0.001); deep venous thrombosis was less frequent with apixaban (2.4% vs. 4.4%), as was pulmonary embolism (1.7% vs. 5.8%). Major bleeding occurred more often with apixaban (3.5% vs. 1.8%; HR, 2.0; P=0.046). No between-group differences were seen in the rates of adverse events and deaths.

Comment: Patients with active malignancies are at risk for VTE but do not always receive prophylactic anticoagulants because of concerns about bleeding, need for injections, and cost. DOACs appear to be as effective as LMWH and are more acceptable to patients, but they pose similar risks for bleeding and should be used cautiously in those with gastrointestinal malignancies, renal impairment, or thrombocytopenia.

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James Yeh, MD MPH, Physician at NEJM Group
James Yeh, MD MPH is an internist and assistant in medicine at the Massachusetts General Hospital and an instructor in medicine at Harvard Medical School. His clinical and academic interests are in evidence-based medicine, medical education, continuing medical education, cardiopulmonary diseases, cardiovascular risk reduction, critical illness, care transition, polypharmacy, and health communication. He was a NEJM editorial fellow in 2015-2016.