New ASH Guidelines: VTE Prevention, Treatment in Cancer Patients

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New guidelines from the American Society of Hematology “strongly recommend” using no thromboprophylaxis over using parenteral thromboprophylaxis in ambulatory patients receiving cancer chemotherapy who have low venous thromboembolism (VTE) risk, and using no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists in those at any VTE risk level.

The evidence-based guidelines for the prevention and treatment of VTE in patient with cancer, published online in Blood Advances, also include a “conditional recommendation” for using either thromboprophylaxis with the direct oral anticoagulants (DOACs) apixaban or rivaroxaban or using no thromboprophylaxis in ambulatory patients with intermediate risk and using the DOACs over no thromboprophylaxis in those with high VTE risk.

The purpose of the guidelines, which also address VTE prophylaxis in hospitalized patients with cancer and the use of anticoagulation for VTE treatment in patients with cancer, is to provide clinical decision support for shared decision-making by patients and clinicians, Gary H. Lyman, MD, of Fred Hutchinson Cancer Research Center, Seattle and Marc Carrier, MD, of the University of Ottawa, and their colleagues from the multidisciplinary guidelines panel explained.

“The recommendations take into consideration the strength of the evidence, risks of mortality, VTE, and bleeding, as well as quality of life, acceptability, and cost considerations,” they wrote, noting that VTE is a common complication in patients with cancer, who are at markedly increased risk for morbidity and mortality from VTE.

Levels of Evidence

The panel members relied on updated and original systematic evidence reviews. Conditional recommendations, as opposed to strong recommendations, are defined by the panel as “suggestions,” and all 33 recommendations that make up the guidelines include a statement on the strength of the relevant evidence.

For example, the thromboprophylaxis recommendations for low, intermediate, and high VTE risk are made based on “moderate certainty in the evidence of effects,” and the recommendation for no thromboprophylaxis over oral thromboprophylaxis with vitamin K antagonists is a strong recommendation based on “very low certainty in the evidence of benefits, but high certainty about the harms.”

The guidelines panel also strongly recommends, based on moderate certainty in the evidence of effects, using low-molecular-weight heparin over unfractionated heparin for the initial treatment of VTE in patients with cancer, and suggests, based on “very low certainty in the evidence of effects,” using LMWH over fondaparinux in this setting.

In addition to primary prophylaxis in ambulatory and hospitalized patients and initial VTE treatment, they also address primary prophylaxis for patients with cancer who have a central venous catheter, VTE treatment in surgical patients with cancer, short-term VTE treatment, and long-term VTE treatment.

For example, the guidelines panel conditionally recommends:

Not using parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter
Using LMWH or fondaparinux for surgical patients with cancer
Using DOACS for the short-term treatment of VTE, and LMWH or DOACs for the long-term treatment of VTE in patients with cancer.

The Perils of VTE

VTE in patients with cancer can interfere with treatment, increase mortality risk, and increase costs, the authors noted, adding that VTE can also adversely affect cancer patients’ quality of life.

“Some have even reported the experience of VTE to be more upsetting than that of the cancer,” they wrote. “More than 50% of thrombotic events occur within 3 months of the cancer diagnosis, a time when most cancer treatments will be underway. Patients, who are still coming to terms with a recent cancer diagnosis, often view the occurrence of VTE as a further threat to life, confirmation of the severity of their condition, and a poor prognostic sign.”

Therefore, the new guidelines aim to reduce VTE frequency, risk of bleeding complications, morbidity, and costs, thereby improving quality of life and the patient experience, the authors said, noting that three other recent guidelines on VTEs in patients with cancer have been published: the 2019 American Society of Clinical Oncology guidelines, the 2019 International Initiative on Thrombosis and Cancer guidelines, and the 2020 National Comprehensive Cancer Network guidelines.

The ASH guidelines are similar in many ways to the other guidelines, but differ in some ways, as well. An example is the timing of initiation of pharmacological thromboprophylaxis in patients undergoing cancer-related major abdominal surgery. The ASCO and ITAC guidelines advise starting thromboprophylaxis preoperatively, whereas the ASH guidelines recommend initiating thromboprophylaxis postoperatively, citing “the limited advantages to initiating thromboprophylaxis preoperatively, in addition to the potential bleeding and logistical considerations associated with neuraxial anesthesia.”

These differences highlight a lack of data in that setting and the need for additional studies, the authors said.

ASH vs. ASCO

James Douketis, MD, a practicing clinician and professor of medicine at McMaster University, Hamilton, Ont., highlighted another difference between the ASH and ASCO guidelines.

“For the treatment of [cancer-associated thrombosis], ASCO gives a strong recommendation to use LMWH or DOACs (with some caveats), which is easy to follow. ASH, on the other hand, suggests LMWH or a DOAC for the first 7-10 days, DOACs for the first 3-6 months, and back to LMWH or DOACs after 6 months,” he said in an interview.

The recommendation is “very evidence based but ambiguous and not helpful for the practicing clinician,” added Douketis, who helped develop the ITAC guidelines, but was not part of the ASH or ASCO guideline panels.

ASCO also provides a clear recommendation for giving VTE prophylaxis for 4 weeks after cancer surgery in patients with high VTE risk, whereas ASH gives “a somewhat vague recommendation” for thromboprophylaxis after hospital discharge.

The guidelines are “pretty well aligned” with respect to recommendations on VTE prophylaxis in medical cancer patients receiving chemotherapy, and although the “extremely academic” ASH guidelines were developed by “a superb team using the same evidence and excellent methodology,” they are interpreted in slightly different ways and fall short when it comes to being clinician friendly, Douketis said.

“At the end of day, for practicing clinicians, the ASH guidelines don’t provide a message that’s easy to digest,” he added.

ASH has, however, provided a resource page that includes tools and information for implementing the guidelines in clinical practice, and will maintain the guidelines “through surveillance for new evidence, ongoing review by experts, and regular revisions,” the authors said.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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