Administering pharmalogic prophylaxis with enoxaparin in addition to elastic stockings and graduated compression to acutely ill patients did not reduce the rate of mortality, according to a study published Dec. 29 in the New England Journal of Medicine. However, the authors did determine that pharmalogic thromboprophylaxis showed benefit in preventing venous thromboembolism.
“Although thromboprophylaxis reduces the incidence of venous thromboembolism in acutely ill medical patients, an associated reduction in the rate of death from any cause has not been shown,” Ajar K. Kakkar, PhD, of the University College London, and colleagues wrote.
To evaluate the outcomes of 40 mg of subcutaneous enoxaparin (Lovenox, Sanofi-Aventis) compared with placebo, Kakkar and colleagues enrolled 8,307 patients into the international, multicenter, randomized double blind LIFENOX trial. Patients received enoxaparin plus elastic stockings with graduated compression (4,171 patients) or placebo (4,136 patients). Enrolled patients were at least 40 years old and had been hospitalized for acute decompensated heart failure, severe systemic infection with at least one venous thromboembolism risk factor. The study took place at 193 sites throughout China, India, Korea, Malaysia, Mexico, the Philippines and Tunisia.
The study’s primary endpoint was the rate of death from any cause at 30 days after randomization and the primary safety outcome was the rate of major bleeding up to 48 hours post-treatment.
The researchers reported that the rate of death at 30 days was 4.9 percent in the enoxaparin group vs. 4.8 percent in the placebo group. The incidence of death from cardiopulmonary causes and the rate of sudden death or pulmonary embolism at 30 days did not statistically differ between the two groups. Of the patients who died, the most common cause was pulmonary failure, which occurred in 2.1 percent of the enoxaparin group and 1.8 percent of patients in the placebo arm. Three patients who received enoxaparin died from a hemorrhage.
Major bleeding events were reported in 16 patients who received enoxaparin and 11 patients who received placebo. Rates of minor bleeds were higher in the enoxaparin arm compared with the placebo arm, and the combined rates of bleeding events were higher in the enoxaparin group.
Adverse event rates occurred in 37.8 percent of the patients who received enoxaparin and 36.9 percent of those who received placebo.
“Pharmacologic prophylaxis was not associated with increased rates of major bleeding but was associated with increased rates of total bleeding,” the authors noted. “These findings appear to be counterintuitive, given the fact that pharmacologic prophylaxis has been shown to reduce the risk of venous thromboembolism, including asymptomatic deep-vein thrombosis, by at least 45 percent in hospitalized, acutely ill medical patients.”
The authors speculated that it could be possible that the use of elastic stockings with graduated compression is effective in preventing venous thromboembolism, which could reduce the rate of fatal pulmonary embolism.
Kakkar and colleagues concluded that the results of the LIFENOX trial did not statistically differ between acutely ill medical patients who were assigned to prophylaxis with enoxaparin in addition to elastic stockings or those who were assigned to receive elastic stockings with graduated compression alone.
Thromboprophylaxis showed benefit in the prevention of venous thromboembolism. This could reduce the need to treat symptomatic venous thromboembolism with high doses of anticoagulants, according to the authors.
“Furthermore, venous thromboembolism can lead to nonfatal complications such as the post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension, which are often not treated successfully,” Kakkar and colleagues summed.