Researchers at University College London (UCL; United Kingdom) and other institutions conducted a placebo-controlled, randomized trial to assess the effect of subcutaneous enoxaparin (40 mg daily) as compared with placebo--both administered to 8,307 patients who were wearing elastic stockings with graduated compression--on the rate of death from any cause at 30 days among hospitalized, acutely ill patients at participating sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia. Inclusion criteria were age of at least 40 years, hospitalization for acute decompensated heart failure (HF), and severe systemic infection with at least one risk factor for venous thromboembolism, or active cancer.

The results showed that the rate of death from any cause at day 30 was 4.9% in the enoxaparin group, as compared with 4.8% in the placebo group; two-week all-cause mortality was similar in the two groups, at 2.9% in each, and three-month all-cause mortality was also similar, with a hazard rate of 8.4% for patients receiving thromboprophylaxis and 8.6% for those receiving placebo. The rate of major bleeding was 0.4% in the enoxaparin group and 0.3% in the placebo group. Analysis revealed that pulmonary failure was the most common cause of death at 30 days; other causes included active cancer, impaired kidney function, two or more coexisting acute illnesses, and chronic pulmonary disease. The study was published in the December 29, 2011, issue of the New England Journal of Medicine (NEJM).

“While thromboprophylaxis in surgical patients has been shown to decrease the rate of lethal pulmonary embolism, acutely ill medical patients may be at risk for death from many causes other than pulmonary embolism, thus diminishing the ability of pharmacologic prophylaxis to improve the overall clinical outcome,” concluded lead author Ajay Kakkar, MBBS, PhD, of UCL, and colleagues. “Another possible reason for the lack of a benefit could be that rates of pulmonary embolism have been reported to be lower in Asia than in Western countries.”

Heparin is a highly sulfated glycosaminoglycan, widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. Although it is used principally in medicine for anticoagulation, its true physiological role in the body remains unclear, because blood anticoagulation is achieved mostly by heparan sulfate proteoglycans. It has been proposed that, rather than anticoagulation, the main purpose of heparin is defense at such sites against invading bacteria and other foreign materials.

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