Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery
M. N. Levine, M. Gent, J. Hirsh, J. Weitz, A. G. Turpie, P. Powers, J. Neemeh, A. Willan and P. Skingley
Department of Medicine, McMaster University, Hamilton, Ontario.
BACKGROUND: Deep vein thrombosis is common in patients undergoing major
knee surgery. Static graduated compression stockings effectively prevent
venous thrombosis in general surgery. Because of the demonstrated
prophylactic efficacy of pneumatic compression in knee surgery, the similar
efficacy of static graduated compression and pneumatic compression in
neurosurgery, and the easier use of static graduated compression in knee
surgery, graduated static compression stockings were used as the control
arm in our clinical trial. Although low-molecular-weight heparin had been
shown to be effective in general surgery and hip replacement, its efficacy
was unproved in knee surgery. METHODS: A double-blind, randomized trial
compared the combination of low-molecular-weight heparin and graduated
compression stockings with graduated compression stockings alone in
patients undergoing major knee surgery. Patients received either ardeparin
(Normiflo) (low-molecular-weight heparin), 0.005 mL/kg (50 anti-Xa U/Kg),
or placebo. Both were administered subcutaneously twice daily commencing 12
to 24 hours after surgery and continued for 14 days or until discharge, if
sooner. Both study groups wore graduated compression stockings. Bilateral
venography was performed on day 14, or sooner if the patient was ready for
discharge. RESULTS: One hundred twenty-two patients were allocated to
receive ardeparin and 124 received placebo. Ninety-six patients in the
ardeparin group and 103 in the placebo group had evaluable venograms. Deep
vein thrombosis was detected in 28 patients in the ardeparin group and in
60 in the placebo group. Proximal deep vein thrombosis was detected in two
patients who received ardeparin and 16 who received placebo. One patient in
each group, both of whom did not have venography, experienced pulmonary
embolism. Thus, deep vein thrombosis or pulmonary embolism was detected in
29 (29.9%) of the 97 patients in the ardeparin group and in 61 (58.7%) of
the 104 patients in the placebo group, a relative risk reduction of 49% (P
< 00.1). The rate of major bleeding in the ardeparin group was 2.5%,
compared with 2.4% in the placebo group. CONCLUSION: Ardeparin administered
postoperatively twice daily is effective and safe for the prevention of
venous thrombosis in patients undergoing major knee surgery. Whereas
graduated compression stockings have been shown to be effective
prophylactic agents in general surgery and neurosurgery, they have little
effect in knee surgery.
