Venous thromboembolism is the biggest mortality risk besides cancer itself, but bleeding also kills.
Anticoagulant-related bleeding in cancer patients is tied to a threefold risk of early death compared to patients without a bleed, according to new research in the American Journal of Hematology.
Cancer patients are at an increased risk of venous thromboembolism, but data has so far been sparse on the links between anticoagulant use and survival in these patients.
“Clinicians [have to] carefully weigh the risk of clot-related complications (morbidity and death) against the risk of major bleeding, which can also be life-threatening,” said Associate Professor Marliese Alexander, deputy director of pharmacy (quality and research) at the Peter MacCallum Cancer Centre.
“This is a significant issue for our patients, [as] cancer-associated clots, or complications of these clots, is the highest cause of death for patients with cancer – other than the cancer itself.”
Researchers used data from more than 9000 patients with a solid tumour and newly diagnosed VTE who were in the US Veterans Affairs healthcare system to retrospectively examine the association between anticoagulant-related bleeding events requiring hospitalisation and death within a year of starting the anticoagulant therapy.
The median age of included patients was 68 years. Lung cancer was the most common type of cancer (28%), followed by prostate (13%) and lower gastrointestinal cancers (11%). Roughly a third of patients underwent chemotherapy.
All patients had been prescribed direct oral anticoagulants, low molecular-weight heparin or vitamin K antagonists for at least 30 days within 30 days of being diagnosed with VTE. The majority of patients received LMWH (53%) or a DOAC (24%).
Professor Alexander told Oncology Republic that there were several key factors that influenced clinician decision-making on whether to prescribe anticoagulative therapies, including:
- the choice and dose of anticoagulant: “some agents are more easily reversed or have lower bleeding risks, [and] lower doses may be considered in patients with bleeding risks”
- how bleeding risks are managed: “for example, in patients with thrombocytopenia, platelet transfusions may be given to safely allow anticoagulation”
- multidisciplinary decision-making: “haematologists, oncologists and other specialists collaborate to tailor anticoagulation therapies based on the patient’s overall condition, prognosis and goals of care”
One in 12 patients developed clinically significant bleeding that required hospitalisation within 12 months of starting anticoagulant therapy; 56% of these patients experienced a GI bleed, 20% experienced a genitourinary bleed, and 11% experienced an intracranial haemorrhage. Among those who experienced a bleed there were more patients with a history of alcohol abuse, anaemia, stroke, liver disease or uncontrolled hypertension than among the patients who did not.
More than one in five patients died within 12 months of initiating anticoagulation therapy. The median overall survival was shorter for patients with a clinically significant bleed compared to those without a bleed (10 vs 15 months).
After controlling for the impact of potential confounders, having an anticoagulant-related bleeding event meant patients were more than twice as likely to die (adjusted hazard ratio 2.91) within 12 months compared to patients who did not have a bleeding event.
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The location of the bleeding event was also associated with mortality. Patients who experienced an intercranial haemorrhage were nearly six times more likely to die, and patients who experienced a GI bleed nearly three times more likely to die, than patients who did not experience a bleed.
“In the absence of reliable bleeding risk assessment models in cancer patients, the findings underscore the importance of individualised risk assessment and vigilant monitoring in managing anticoagulant therapy in this frail population,” the researchers concluded.
Professor Alexander agreed with the researchers’ conclusion about the need to take a tailored approach to treatment to balance the risks of clotting and bleeding, and said the findings added to the body of evidence supporting continued efforts to optimise both prevention and treatment strategies.
“In the prevention setting (primary prophylaxis), much lower doses of anticoagulants are used, significantly reducing bleeding risks while still preventing VTE,” Professor Alexander said.
“Where supported by the evidence, primary prevention is preferred to avoid the complications of VTE and the need for high-dose therapeutic anticoagulation.”
