In a multicenter, double-blind clinical trial in 1,968 inpatients 1 daily subcutaneous administration of LMW
heparin plus 2 placebo
injections or 3 x 5,000 IU unfractionated (UF)
heparin was given for 10 (8-11) days. The primary end point was the incidence of proximal
deep-vein thrombosis or
pulmonary embolism. Patients were assessed during the study period for development of proximal
deep-vein thrombosis by compression sonography at days 1 and 10 and for
pulmonary embolism by scintigraphy in symptomatic patients. Aim of the study was to demonstrate the equivalence of both treatment regimens. A total of 1,968 patients were randomized to receive UF or LMW
heparin. Of these, 378 patients were excluded during the study period, so that 780 patients on UF and 810 on LMW
heparin were included in the efficacy analysis. Four primary end points were observed with UF and 6 with LMW
heparin, demonstrating the equivalence of treatments (p = 0.012). Additionally,
pulmonary embolism was suspected as the cause of death in 6 patients who died during the study (3 per treatment group). A higher frequency of death (n = 32) was observed in the LMW-
heparin group (p = 0.02) particularly documented in a part of the centers. Safety analysis showed a higher frequency of local
pruritus, local
erythema and subcutaneous
hematoma, a higher increase in plasma levels of
triglycerides, total
cholesterol,
alanine aminotransferase and
aspartate aminotransferase, and a decrease of
antithrombin III in patients receiving UF
heparin. A decrease in platelet count (values ranging between 40,000 and 80,000/microliter) was observed in 4 patients with UF and in none with LMW
heparin. No severe
thrombocytopenia was observed. Subcutaneous LMW
heparin is as effective as UF
heparin for prophylaxis of
thromboembolism in bedridden, hospitalized medical patients.