EFFICACY AND SAFETY OF LOW-MOLECULAR-WEIGHT HEPARIN (ARDEPARIN SODIUM) COMPARED TO WARFARIN FOR THE PREVENTION OF VENOUS THROMBOEMBOLISM AFTER TOTAL KNEE REPLACEMENT SURGERY - A DOUBLE-BLIND DOSE-RANGING STUDY

We performed a double-blind, randomized clinical trial to compare the efficacy and safety of three different subcutaneous (SC) low molecular weight heparin doses (ardeparin sodium 25, 35, or 50 anti-X(a) U/kg t wice 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 discovere d at postoperative venography of the operated leg, or symptomatic, obj ectively-documented pulmonary embolism. Of 860 patients randomized, 68 0 (79%) had an evaluable venogram or pulmonary embolism. The total ven ous thromboembolism prevalence was significantly greater among patient s 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, res pectively. Overt bleeding occurred in 22 (7.9%) ardeparin 50 BID patie nts compared to 12 (4.4%) warfarin patients (p = 0.08), and in seven a rdeparin 25 and 35 BID patients each (5.2% and 5.0%, respectively). Co mpared 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 ard eparin 50 anti-X(a) U/kg SC BID is significantly more effective than a djusted-dose warfarin for this indication. Although overt bleeding amo ng warfarin and ardeparin 50 BID patients did not differ significantly , ardeparin 50 BID patients had significantly greater blood loss. Arde parin 35 anti-X(a) U/kg SC BID may provide efficacy similar to ardepar in 50 anti-X(a) U/kg SC BID but with reduced bleeding.