Venous Thromboembolisms (VTEs) rise in cancer patients on chemotherapy


The risk of venous thromboembolism (VTE) almost doubled over an 8.5-month period among cancer patients receiving chemotherapy, a retrospective cohort study showed.

VTE incidence increased from 7.6% at 3.5 months to 13.5% at 12 months, rates higher than those observed in clinical trials.

Patients who developed VTE also had an increased risk of bleeding at 3.5 and 12 months compared with patients who did not have embolic complications, Gary H. Lyman, MD, of Duke University and co-authors reported online in The Oncologist.

"The VTE rates reported in our study are much higher than those observed in randomized clinical trials," the authors said of their findings.

"The development of VTE in patients with cancer may interfere with planned active treatment, may increase patient morbidity and early death rates, and may worsen quality of life," they added. "These results highlight that VTE prevention is not only important for reducing the thrombosis risk but probably also for preventing the bleeding risk associated with thrombosis and its therapy."

Malignancy is associated with a hypercoagulable state that increases the risk of VTE by at least four-fold as compared with people without cancer. Other factors that can affect VTE risk include age, obesity, history of thrombosis, recent reduced mobility, and major surgery.

The type of cancer treatment also influences VTE risk. Chemotherapy, for example, can boost the risk by as much as 6.5-fold. Moreover, VTE risk varies throughout the disease course, the authors noted in their introduction. The risk is particularly elevated in the first months after diagnosis and in patients who have late-stage, metastatic disease.

Finally, VTE risk varies by the type of cancer. Hematologic malignancies carry the highest risk, followed by lung, pancreatic, stomach, ovarian, uterine, bladder, and brain cancer.

Reported VTE rates have ranged from 2% to 12% in different populations of patients with cancer, the authors continued.

"It is therefore anticipated that a subset of patients with cancer who have additional VTE risk factors and are undergoing chemotherapy are at high risk for VTE," said Lyman and co-authors. "Thromboprophylaxis use is sporadic and not routine, and patients with cancer are usually treated with curative doses when symptomatic VTE events occur."

Neither North American nor European clinical guidelines recommend routine thromboprophylaxis for outpatients receiving chemotherapy. However, both the National Comprehensive Cancer Network and the American Society of Clinical Oncology recently suggested that thromboprophylaxis warrants consideration for high-risk ambulatory cancer patients.

To provide a "real-world" estimate of VTE risk in chemotherapy-treated cancer patients, Lyman and colleagues searched a large healthcare claims database encompassing records for more than 100 million people in managed care plans. They limited the search to patients with cancer of the lung, pancreas, stomach, colon/rectum, bladder, or ovary and who started chemotherapy from January 2005 through December 2008.

Using ICD-9 diagnostic codes, investigators identified cancer patients who had at least one claim related to VTE. Patients were followed from the initiation of chemotherapy to 12 months.

Investigators used three different definitions to define VTE. The least stringent definition relied solely on the presence of one or more claims for VTE.

The intermediate definition limited cases to patients who had two or more outpatient claims at least 30 days apart, one inpatient claim, or one outpatient claim associated with administration of an anti-coagulant within 90 days.

The most stringent definition excluded any VTE that occurred within 90 days of major or invasive surgery.

Data analysis included 27,479 patients who had a mean age of 62. Men accounted for 52% of the study population, and half of the patients had metastatic disease. Demographic and clinical characteristics did not differ between patients who developed VTE and those who did not, the authors reported.

By the least stringent definition, the overall VTE rate at 3.5 months was 7.3%. By the intermediate and strict definitions, the rates were 3.4% and 3.2%, respectively. Regardless of definition, higher rates were seen in patients with pancreatic, lung, and stomach cancers.

The least stringent definition of VTE was associated with the highest VTE rate at 12 months (13.6%), whereas the intermediate (7.1%) and strict (6.7%) definitions were associated with lower and similar rates.

Patients with VTE had a higher risk of major bleeding within 12 months as compared with patients who did not have VTE, and the difference held up irrespective of VTE definition.

By the least stringent definition, the patients who had VTEs within the first 3.5 months had a bleeding incidence at 3.5 months compared with patients who did not have a VTE (11.0% versus 3.8%). At 12 months the bleeding rates were 19.8% in patients with VTE and 9.6% in patients without VTE.

VTE was associated with significantly higher healthcare costs. In the 12 months prior to starting chemotherapy, patients who subsequently developed VTE (most lenient definition) had mean overall costs of $35,476 versus $33,618 for patients who did not develop VTE.

At 12 months, total costs averaged $110,719 for patients who developed VTE and $76,804 for those who did not (P<0.0001).

Cancer researchers and clinicians have known that cancer patients have an increased risk of VTE, but the study quantified the risk to an extent not previously reported.

"What we didn't know was the prevalence of patients who are ambulatory, outpatients getting chemotherapy," Sahil Parikh, MD, of University Hospitals-Case Medical Center in Cleveland, told MedPage Today. "We thought the risk was relatively low, 1% to 3%. The mean [in this study] was about 7% at 3.5 months and up to 12% at one year. Quite a substantial risk, and that is what I think is additive about this real-world database."

Nonetheless, the results require some caution in interpretation.

"Not only do these patients who develop VTE have higher incidences than we thought, but they also have higher incidences of bleeding complications than we thought," said Parikh. "Those two possibly paradoxical findings need to be adjusted when people are thinking about therapy."


Source: MedPage Today:

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