For elderly patients, the risk of dying from a major bleeding event following a cancer-related venous thromboembolism (VTE), although low, is substantially higher than the risk for death from a recurrent VTE, a fact that raises questions about the use of anticoagulants in some patients.
MADRID – For elderly patients, the risk of dying from a major bleeding event following a cancer-related venous thromboembolism (VTE), although low, is substantially higher than the risk for death from a recurrent VTE, a fact that raises questions about the use of anticoagulants in some patients.
"The use of anticoagulants in cancer patients 65 years or older with thrombosis results in at least nine times higher mortality if they develop a major bleeding event compared to a VTE recurrence," said first author Alejandro Lazo-Langner, MD, of Western University, in London, Ontario, Canada. The findings come from a retrospective study he presented here at the European Hematology Association (EHA) 2017 Congress.
The risk for a VTE is known to be higher in cancer patients. However, the risk of bleeding is also high, owing to various causes, including abnormal tumor anatomy and the use of chemotherapy agents linked to an increased thrombocytopenia risk. These factors bear consideration when weighing the risks and benefits of the use of anticoagulants after a VTE, he explained.
Previous research has suggested that the risk for death related to a recurrent thrombosis after the initial event is similar to the risk for death from a major bleeding event, but these previous studies have various limitations, Dr Lazo-Langner commented. Hence, he set out with colleagues to further explore the relationship between these risks and the use of anticoagulants.
The team conducted a retrospective population-based cohort study in Ontario, Canada, using deidentified linked administrative healthcare databases at the Institute for Clinical Evaluative Sciences.
Their study involved 6967 VTE events identified among cancer patients older than 65 years between 2004 and 2014 who had experienced a VTE within 6 months of their initial cancer diagnosis and who were treated with an anticoagulant within 7 days of the VTE. Their treatment regimens included low-molecular-weight (LMW) heparin, used in 60% of patients, LMW heparin followed by warfarin, in 15.3%; warfarin, in 22.1%; rivaroxaban (Xarelto, Janssen), in 2.7%.
The mean age of the patients was 75 years, and about half (52%) were men.
Major bleeding events included upper and lower gastrointestinal and intracranial bleeding events.
At a follow-up of 6 months following the index VTE, the team found significantly fewer major bleeding events (n = 235; 3%) than VTE recurrences (n = 1184; 17%).
However, the rates of mortality within 7 days of the VTE or bleeding event were 0.5% for VTE recurrences and 11% for major bleeding events, with a 7-day mortality rate ratio of 21.8 (95% confidence interval, 9 - 53).
An exploratory analysis showed no differences in rates with respect to the type of anticoagulant prescription used, the authors noted.
Dr Lazo-Langner underscored the fact that the findings are specific to older patients.
It's important to keep in mind that this study only involved cancer patients over 65. Dr Alejandro Lazo-Langner
"It's important to keep in mind that this study only involved cancer patients over 65, so it might be different for younger patients because they may be able to better tolerate bleeding events," he told Medscape Medical News.
Furthermore, despite the much higher risk for death with major bleeding events, the numbers were still low, he added.
"In terms of the risk, we found the bleeding events were very low – about six times lower than the thrombotic events in this cohort ― but they were more lethal. So even in a cohort of this size, it's hard to draw a conclusion," he said.
Ultimately, the individual needs of the patient should guide the decision on the use of anticoagulants, Dr Lazo-Langner added.
"The general agreement is that patients who have had a cancer-related clot should remain on anticoagulation long term for as long as the cancer is active," he explained.
"So even though a major bleeding event is more lethal, the risk is still fairly low, and I think in the acute setting, it doesn't make any sense not to treat patients.
"But considering these findings, one might want to consider having the patient only on anticoagulants for a limited amount of time, perhaps 6 months."
Approached for comment, Alok Khorana, MD, an oncologist with the Cleveland Clinic Taussig Cancer Institute, in Ohio, said that the study underscores the known relationships between cancer and thrombotic events but does not prove causation.
"Cancer patients are well known to be at high risk for both VTE and bleeding. The study reinforces the impact of these complications on outcomes in cancer patients," he told Medscape Medical News. "It should be noted that cancer patients have high risk of bleeding with and without anticoagulation, so the [higher risk for mortality with major bleeding] is more of an association rather than causal effect, at least in this dataset."
That being said, the findings do not suggest changes in practice, Dr Khorana noted. "I would consider this hypothesis-generating, and it should not affect clinical decision making," Dr Khorana said.
"I would note that in multiple randomized trials of anticoagulation, safety issues have not been of substantial concern, although certainly trials tend to involve healthier subjects than in the 'real world.' "
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr Lazo-Langner was supported in part by a grant from the Canadian Institutes of Health Research. Dr Khorana has relationships with Janssen, Sanofi, Bayer, Pfizer and Leo Pharma. Dr Khorana has relationships with Janssen, Sanofi, Bayer, Pfizer, and Leo Pharma.
European Hematology Association (EHA) 2017 Congress. Abstract S441. Presented June 24, 2017.