A study by Mayo Clinic researchers provides some clarity on the use of direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, to treat acute venous thromboembolism (VTE) in patients with gastrointestinal cancers. The findings were published 2 June in Mayo Clinic Proceedings.
Among the study’s findings:
- Rivaroxaban showed no higher risk of bleeding in luminal gastrointestinal cancer and should not be considered contraindicated in this group of patients.
- Apixaban showed a higher risk of bleeding in patients with luminal gastrointestinal cancer, and it should be used with great caution to treat this type of cancer until more studies are available to establish its safety.
- DOACs can be used in patients with VTE and non-luminal gastrointestinal cancers, such as pancreatic cancer and hepatobiliary cancer. This is similar to the way patients with non-gastrointestinal cancers are treated for venous thromboembolism.
“It is well known that nearly one in five patients with cancer will develop either a deep vein thrombosis or pulmonary embolism,” says Waldemar Wysokinski, a cardiologist at the Mayo Clinic in Rochester, USA. “Clotting events can be deadly, with pulmonary embolism being the second most common cause of death in cancer patients.”
Wysokinski says patients with cancer who are treated with anticoagulants for VTE have a higher risk of a new clot formation and bleeding, and every anticoagulant should be specifically checked for its effectiveness and safety in this group of patients.
“In the past, the front-line treatment for VTE in patients with cancer was low-molecular-weight heparin [LMWH] injected via syringe,” says Wysokinski. “However, between 2018 and 2020, three new anticoagulants—edoxaban, rivaroxaban, and apixaban—previously approved by the FDA [US Food and Drug Administration] for VTE treatment were specifically evaluated in patients with cancer-associated VTE and found to be non-inferior to LMWH, specifically dalteparin.”
Wysokinski notes that in the randomised clinical trial with rivaroxaban, a safety analysis of patients treated with this blood thinner identified four major bleeding events that occurred among 11 patients, or 36% of patients, whose cancers were located in the upper portion of the gastrointestinal tract (oesophagus or oesophagus-stomach junction) compared to one major bleeding event in 19 patients, or 11% of patients, treated with LMWH. This observation resulted in excluding patients with this type of cancer from further enrolment in this trial.
Wysokinski details that a retrospective analysis of patients with gastrointestinal cancer enrolled in a study comparing efficacy and safety of another DOAC—edoxaban—to LMWH showed a nearly fourfold higher risk of major bleeding in patients treated with this blood thinner, compared to patients treated with LMWH.
“These two observations prompted changes in medical guidelines recommending against using DOACs such as rivaroxaban or edoxaban in patients with gastrointestinal cancer in favour of LMWH,” says Wysokinski. “We felt that these recommendations were based on a very small number of patients and that the findings would require further evaluation to define if restrictions on the use of DOACs applied to all blood thinner of this category—and to the whole group of patients with gastrointestinal cancers or only to patients with luminal gastrointestinal cancers.”
At the time his team completed its analysis and submitted their study for publication, Wysokinski states that there were no studies of patients with cancer-associated VTE that compared apixaban to LMWH in a subgroup of patients with gastrointestinal cancer. He says that while the current study showed no higher risk of bleeding in patients with luminal gastrointestinal cancer treated with rivaroxaban, there was a higher risk of bleeding in patients treated with apixaban.
“Our study does not support the observations of previous clinical trials of rivaroxaban, but it does raise concerns regarding the use of apixaban in this type of cancer and indicates the need for further studies to establish its safety,” comments Wysokinski.
