Data show that heparin prophylaxis is cost-effective in decreasing the incidence of thromboembolism in patients who have had surgery. While heparin prophylaxis is generally recommended in medically ill patients at high risk of thromboembolism, evidence for its efficacy in this setting is lacking. To evaluate the efficacy and safety of enoxaparin in medically ill hospitalized patients, Samama and colleagues performed a randomized, placebo-controlled trial of this agent.
The 1,102 patients in the multicenter study were more than 40 years of age and were expected to be in the hospital for at least six days but not to be immobilized for more than three days. Patients eligible for the study were required to have class III or class IV congestive heart failure, acute respiratory failure that did not require mechanical ventilation or a risk factor for thromboembolism, plus one of the following conditions: acute infection without septic shock, acute rheumatic disorders (including acute lumbar pain, sciatica, vertebral compression or rheumatoid arthritis of the lower extremities) or an episode of inflammatory bowel disease. Risk factors for thromboembolism included age more than 75 years, obesity, previous venous thromboembolism, varicose veins or hormone therapy (except postmenopausal hormone replacement therapy). Of the 1,102 patients, 1,068 had at least one risk factor for venous thromboembolism. The mean number of risk factors per patient was 2.0.
Enoxaparin was given subcutaneously in a daily dosage of 20 or 40 mg. Therapy was initiated within 24 hours of hospitalization and was scheduled to last from six to 14 days while the patient was in the hospital. Patients received placebo or enoxaparin for a median of seven days.
The primary outcome was the occurrence of venous thromboembolism, defined as deep venous thrombosis, pulmonary embolism, or both, that occurred between day 1 and day 14. The secondary outcome was the occurrence of deep venous thrombosis or pulmonary embolism between day 1 and day 110 of hospital admission. Other outcomes assessed were death, major or minor hemorrhage and thrombocytopenia. Follow-up by telephone or in person was conducted between day 83 and day 110 after discharge.
The primary outcome was assessable in 866 patients. The incidence of deep venous thrombosis or pulmonary embolism by day 14 was 5.5 percent (16 of 291 patients) in those who received 40 mg of enoxaparin per day, compared with an incidence of 14.9 percent (43 of 288 patients) in the placebo group. There were 100 cases of deep venous thrombosis detected by day 14, and four cases of symptomatic nonfatal pulmonary embolism. Three cases of pulmonary embolism occurred in the placebo group, and one case occurred in a patient who received 20 mg of enoxaparin. There were no significant differences in primary outcome between the 20-mg treatment group and the placebo group.
Compared with the placebo group, the 40-mg treatment group had a significant reduction in the incidence of all venous thromboembolism and proximal and distal deep venous thrombosis during the three-month follow-up period. Between day 15 and day 110 of follow-up, eight additional thromboembolic events occurred in the study population.
By day 110 of follow-up, 142 patients had died: 50 in the placebo group, 51 in the 20-mg group and 41 in the 40-mg group. These differences were not statistically significant. The incidence of major or minor hemorrhage or thrombocytopenia did not differ significantly among the three groups.
The authors conclude that a daily subcutaneous injection of 40 mg of enoxaparin safely reduces the risk of venous thromboembolism in acutely ill hospitalized patients.