We performed a double-blind, randomized clinical trial to compare the efficacy and safety of three different subcutaneous (s.c.)
low molecular weight heparin doses (
ardeparin sodium 25, 35, or 50 anti-Xa U/kg twice daily [BID]) to adjusted-dose
warfarin (international normalized ratio [INR] = 2.0 to 3.0), as
venous thromboembolism prophylaxis after
total knee replacement surgery. The primary endpoint was total
venous thromboembolism prevalence, defined as
deep vein thrombosis discovered at postoperative venography of the operated leg, or symptomatic, objectively-documented
pulmonary embolism. Of 860 patients randomized, 680 (79%) had an evaluable venogram or
pulmonary embolism. The total
venous thromboembolism prevalence was significantly greater among patients prophylaxed with
warfarin compared to
ardeparin 50 BID (38% vs 27%, p = 0.019); the prevalence among
ardeparin 25 BID (37%) and 35 BID (28%) patients was similar to
warfarin and
ardeparin 50 BID patients, respectively. Overt
bleeding occurred in 22 (7.9%)
ardeparin 50 BID patients compared to 12 (4.4%)
warfarin patients (p = 0.08), and in seven
ardeparin 25 and 35 BID patients each (5.2% and 5.0%, respectively). Compared to the
warfarin group, blood loss was significantly greater in the
ardeparin 50 and 25 BID groups, and not different in the
ardeparin 35 BID group.
CONCLUSIONS: Postoperative, unmonitored, fixed-dose
ardeparin 50 anti-Xa U/kg s.c. BID is significantly more effective than adjusted-dose
warfarin for this indication. Although overt
bleeding among
warfarin and
ardeparin 50 BID patients did not differ significantly,
ardeparin 50 BID patients had significantly greater blood loss.
Ardeparin 35 anti-Xa U/kg s.c.BID may provide efficacy similar to
ardeparin 50 anti-Xa U/kg s.c. BID but with reduced
bleeding.