Thromboembolism Risk Doubled in Cancer Patients

Liam Davenport

August 18, 2017

NEW YORK, NY — Cancer patients face a significantly increased risk of arterial thromboembolism in the first 6 months after diagnosis, with the greatest incidence of thromboembolic events seen in lung-cancer patients, results of a US population-based study reveal[1].

The study in more than 275,000 matched pairs of cancer and noncancer patients indicates that cancer patients are more than twice as likely to develop ischemic stroke and/or MI than other patients, although the increased risk disappears 1 year after diagnosis.

The research, published in the August 15, 2017 issue of the Journal of the American College of Cardiology, also showed that such arterial thromboembolic events are associated with a significantly greater 30-day mortality in cancer patients than in noncancer patients.

There are a number of potential explanations for the increased thromboembolic risk among cancer patients, including shared risk factors such as smoking, age, and obesity, a later stage at diagnosis, and direct induction of a hypercoagulable state by the cancer itself.

Singling out an explanation is made more complex, however, as cancer is not one single disease but many different entities, each with different pathophysiologies.

Speaking to | Medscape Cardiology, lead author Dr Babak B Navi (Weill Cornell Medicine, New York, NY) pointed out that not only does individual cancer histology play a role via its effects on the clotting system but also that cancer treatments vary by cancer type.

"We know that certain cancer treatments appear to increase the risk of heart attack and stroke, and the differences in treatment by cancer type will obviously reflect that," he said.

As a result, Navi feels that, while the findings indicate that cancer patients should be monitored for arterial thromboembolic events, "right now it would be premature to take this data and, across the board, institute blood-thinning medicines or cholesterol-lowering medicines in all patients diagnosed with cancer."

He continued, "That is not justified by the data. This is the first step to figuring out how to reduce the risk of arterial thromboembolism [ATE] in these patients, now that we've clearly demonstrated the heightened risk."

Navi said clinical trials are needed to explore the issues further, as cancer patients are predisposed not only to developing thrombosis but also to bleeding, as chemotherapy can affect their bleeding risk, on top of which they undergo numerous invasive procedures.

"Balancing the risks and benefits of a blood thinner really needs to be worked out in a clinical trial," he said, noting that there are currently a few such trials under way.

"They're still mostly in the early stage, but that's where things begin. I think in a few years, we'll have a better idea of how to treat these patients."

Mining SEER Data

While previous studies have suggested that individual cancers are associated with an increased rate of specific arterial thromboembolic events, there is a lack of broad, population-based data on the overall association between cancer and such events.

Using data from the Surveillance Epidemiology and End Results (SEER) database, linked to Medicare claims from 2002 to 2012, the researchers identified patients newly diagnosed with primary breast, lung, prostate, colorectal, bladder, pancreatic, or gastric cancer or non-Hodgkin's lymphoma, who were matched to Medicare enrollees without the disease by year of birth, sex, race, location of SEER registry, and Charlson Comorbidity Index in the year before study entry. Validated diagnostic codes were used to identify cases of ATE, defined as MI or ischemic stroke.

The 279,719 cancer patients and matched controls (48% male) had a median age of 74 years. At diagnosis, 18% of cancer patients had stage IV disease, although rates varied widely by cancer type. Median follow-up was 2.8 years in the cancer group vs 5.0 years among controls.

The cumulative incidence of ATE at 6 months was 4.7% among cancer patients compared with 2.2% in controls (hazard ratio [HR] 2.2; 95% CI 2.1–2.3, P<0.001).

The highest overall risk of ATE events was seen in lung-cancer patients, at a 6-month cumulative incidence of 8.3% vs 2.4% among controls (P<0.001).

The researchers note that, over time, the excess thromboembolic risk among cancer patients decreased and generally resolved by 1 year.

Further analysis indicated that 6-month cumulative risk of MI in cancer patients vs controls was, at a hazard ratio of 2.9 (95% CI 2.8–3.1; P<0.001), higher than that seen for ischemic stroke, where the hazard ratio was 1.9 (95% CI 1.8–2.0; P<0.001).

In cancer patients, ATE was associated with a significantly increased mortality risk that remained after adjustment for matching factors and cancer stage (HR 3.1; 95% CI 3.0–3.1).

The researchers also calculated that the 30-day cumulative mortality incidence after ATE was significantly higher in cancer patients than in controls, at 17.6% vs 11.6% among controls (P<0.001).

Drs Edward TH Yeh and Hui-Ming Chang (University of Missouri, Columbia) point out in an accompanying editorial that there are a number of limitations to the study, such as its retrospective design and reliance on diagnostic codes[2]. However, they say the findings can be used as a springboard for developing closer cooperation between cardiologists and oncologists to modify patients' cardiovascular risk factors.

"There are a large number of cardiologists who are interested in working more closely with oncologists; in fact, there are many programs of oncocardiology or cardio-oncology in different schools, institutions, and hospitals around the world," Yeh told | Medscape Cardiology.

"These people are interested in exactly what I've advocated for: collaboration between cardiologists and oncologists to take care of cancer patients' heart problems during or after their therapy."

For now, Yeh feels that there are two main issues around the high rate of thromboembolic events in cancer patients, the first being that of prevention.

"Usually, when patients are diagnosed with cancer, the main focus is on treating cancer and, many times, their cardiovascular risk factors are not monitored," he said, adding that cardiovascular complications are "a very important part of optimal cancer therapy, because many cancer therapies can induce cardiovascular complications."

The second major consideration, Yeh said, is that if a patient develops acute coronary syndrome or MI while on cancer therapy, "there is a tendency of not treating them aggressively."

Noting that there are ways of monitoring their bleeding risk and still treating them aggressively, he added "these patients should not be ignored when they develop acute coronary syndrome or myocardial infarction."

The research was supported by the National Institutes of Health (NIH) and the Florence Gould Endowment for Discovery in Stroke. Navi reported no relevant financial relationships. Disclosures for the coauthors are listed in the paper. Yeh is supported by a grant from the NIH. Chang reports that she has no relevant financial relationships.

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