London, UK - Prophylaxis for venous thromboembolism (VTE) in the acute hospital care setting is substantially underused worldwide, a large international trial shows [1]. Results from the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study were first presented at a conference last year and have now been published in the February 2, 2008 issue of the Lancet by Dr Alexander T Cohen (Kings College Hospital, London, UK) and colleagues.

Half the people are left at risk for something that has got a simple, inexpensive—£1 a day—therapy to prevent death. That's pretty striking.

"We found that half of all patients in medical and surgical wards worldwide are at risk of thrombosis—a potentially life-threatening condition—yet only half of them are getting something to stop this. So half the people are left at risk for something that has got a simple, inexpensive—£1 a day—therapy to prevent death. That's pretty striking," Cohen told heartwire. His team also found there were wide geographic variations between countries in terms of the use of VTE prevention and that medical patients were particularly poorly served.

In an accompanying comment [2], Drs Walter Ageno and Francesco Dentali (University of Insubria, Italy) say that while the volume of evidence is growing with regard to the prevention of VTE, "the number of patients receiving adequate prophylaxis is not. To improve the rate of appropriate thromboprophylaxis use, we must determine why practice and recommendations are discordant." They believe one of the main explanations for this is ongoing disagreement about VTE risk among physicians themselves—certain specialties remain to be convinced of the benefits of prophylaxis, as do clinicians in particular countries, they state.

ENDORSE, a multinational cross-sectional survey, was conducted in 32 countries and involved 68 183 patients in 358 hospitals. Cohen said the study was unique in scope, as previous research has focused on "two or three hospitals, this ward or that, these types of patients, whereas we randomly selected institutions and stratified for academic and nonacademic hospitals so we could really see what factors were determining the use of preventive therapies."

Using the 2004 American College of Chest Physicians (ACCP) guidelines and hospital chart review, the patients in ENDORSE were assessed for risk of VTE, and the proportion of at-risk patients who received effective prophylaxis was determined.

The researchers found that the risk for VTE is common—present in 51.8% of patients, including 64.4% of surgical cases and 41.5% of medical patients—but that VTE prophylaxis is underused, with only 58.5% of surgical patients receiving it overall and just 39.5% of medical cases.

Cohen said the results were not that unexpected, as other studies had indicated the problem to a certain extent. "But two things did surprise us. First of all, everyone did worse than they thought. Even the best countries have got big holes. When you talk to people who work in Germany or Switzerland, they say, 'All our patients get thromboprophylaxis,' but then you look at the results and you see, no, they don't. So there is room for improvement even in the good countries.

Even the best countries have got big holes. There is room for improvement even in the good countries.

"The second thing that was striking was that the risk is constant, at around 50%, throughout the world," says Cohen. Bangladesh, India, Pakistan, and Thailand were among the countries with the lowest rates of prescription in ENDORSE, at 16% or lower in surgical patients.

"People always said, 'We don't have patients at risk,' in, for example, Thailand and Bangladesh. But they do. Clearly people don't realize that they've got so many patients at risk and they are not doing much about it," he adds.

Ageno and Dentali concur. "The incidence of postsurgical VTE has long been thought to be low in Asian populations," but recent studies such as AIDA [3] "have challenged this view by showing that, without thromboprophylaxis, the rate of venous thrombosis in patients of Asian origin is similar to that previously reported in Europe and North America," they point out.

Cohen says there are a number of reasons why VTE is often seemingly ignored. "This is a silent, undiagnosed disease that kills people—we get the diagnosis right prior to death only in three out of 10 cases. So in seven out of 10 patients who die of thrombosis, we say it's something else. And it's massively underestimated. Last year we published a paper showing that more than 500 000 people a year in the EU are dying from thrombosis, which is more than twice all the deaths combined from breast cancer, prostate cancer, traffic accidents, and HIV infection.

"If you go out on the street and ask individuals, 'Do people die of thrombosis?' they say, 'No, that's what you get on an airplane.' They are just not aware, and doctors aren't aware. Thrombosis is a complication of heart failure, surgery, and cancer therapy, to name a few. Because of the compartmentalization of medicine, people have become specialists—they know how to look after the heart, for example, but they are not looking at the whole patient."

The use of recommended VTE prophylaxis was particularly poor in medical patients in ENDORSE, a finding that is also consistent with other studies, says Cohen. For example, only 37% of patients with active malignancy and ischemic stroke—two of the highest-risk groups for VTE—received prophylaxis. And even in countries where prevention is commonly provided to at-risk patients, he said, "We noted that rates of prophylaxis were low in medical patients with high-risk conditions such as congestive heart failure."

Cohen says last year he attended the European Society of Cardiology meeting, the European Respiratory Society conference, and the European Society of Medical Oncology meeting to try to raise awareness about thrombosis. "There are no recommendations on preventing thrombosis in heart-failure guidelines, and at the oncology meeting there was not a single abstract or paper on thrombosis, despite it being the second commonest cause of death if you have cancer."

And Ageno and Dentali say that different perceptions of the benefit/risk ratio of pharmacological prophylaxis exist among ischemic stroke specialists, "with some stroke guidelines not recommending routine use of pharmacologic prevention strategies."

"This disagreement . . . is not unique to stroke specialists but also has been an important limitation of VTE prophylaxis by general surgeons, urologists, and others," the Italian doctors say.

"Work is need to improve prevention of VTE in hospitalized patients. Local programs, such as electronic alerts to encourage prophylaxis in daily clinical practice, are effective and should be promoted," they continue.

"However, before these tools can be globally and successfully implemented, the prevalence of hospitalized patients who are at high risk for VTE must be better appreciated, and guidelines supporting the appropriate use of prophylactic strategies should be endorsed by all medical and surgical societies," they conclude.