RD HEPARIN COMPARED WITH WARFARIN FOR PREVENTION OF VENOUS THROMBOEMBOLIC DISEASE FOLLOWING TOTAL HIP OR KNEE ARTHROPLASTY

The efficacy and safety of RD heparin, a low-molecular-weight heparin, for the prevention of venous thromboembolic disease among patients ma naged with an elective total hip or total knee arthroplasty were compa red with the efficacy and safety of warfarin in an open-label prospect ive, multicenter trial. Patients were randomized to receive either a f ixed dose of fifty anti-factor-X(a) units of RD heparin per kilogram o f body weight, administered subcutaneously twice daily, beginning post operatively; a fixed dose of ninety anti-factor-X(a) units of RD hepar in per kilogram of body weight, administered subcutaneously once daily , beginning postoperatively; or five milligrams of warfarin, administe red orally preoperatively, followed by a daily adjusted dose of warfar in to prolong the prothrombin time ratio to 1.2 to 1.5. The primary me asure of efficacy was contrast venography of the treated limb, perform ed by local radiologists blinded to the type of treatment that had bee n assigned. Nine hundred and sixty-nine patients had a complete assess ment for the presence of deep-vein thrombosis. The over-all rates of v enous thromboembolic disease were 16 per cent (95 per cent confidence interval, 13 to 21 per cent) (fifty-three) for the 328 patients who re ceived RD heparin twice daily, 21 per cent (95 per cent confidence int erval, 17 to 26 per cent) (sixty-eight) for the 320 patients who recei ved RD heparin once daily, and 27 per cent (95 per cent confidence int erval, 22 to 32 per cent) (eighty-seven) for the 321 patients who rece ived warfarin (p < 0.001 for RD heparin administered twice daily compa red with warfarin; p = 0.13 for RD heparin administered once daily com pared with warfarin). Compared with warfarin, RD heparin administered twice daily and RD heparin administered once daily reduced the risk of venous thromboembolic disease by 41 per cent (95 per cent confidence interval, 20 to 56 per cent) and 18 per cent (95 per cent confidence i nterval, -6 to 37 per cent), respectively. The rates of venous thrombo embolic disease after 523 total hip arthroplasties were 8, 14, and 14 per cent for the patients who received RD heparin twice daily, those w ho received it once daily, and those who received warfarin (p = 0.07 f or RD heparin administered twice daily compared with warfarin; p = 0.8 2 for RD heparin administered once daily compared with warfarin). The rates after 446 total knee arthroplasties were 26, 30, and 43 per cent , respectively (p = 0.004 for RD heparin administered twice daily comp ared with warfarin; p = 0.04 for RD heparin administered once daily co mpared with warfarin). A fixed dose of fifty anti-factor-X(a) units of RD heparin per kilogram of body weight administered subcutaneously tw ice daily, beginning postoperatively, appeared more effective than low -dose warfarin for the prevention of venous thromboembolic disease fol lowing a major orthopaedic procedure on the lower limb. For the patien ts who had had a total hip arthroplasty, RD heparin administered twice daily and warfarin were equally effective and safe. For the patients who had had a total knee arthroplasty, RD heparin administered twice d aily was significantly more effective than warfarin, although the rate of deep-vein thrombosis remained substantial. There was no difference between RD heparin administered twice daily and warfarin with regard to the rate of clinically important bleeding events. Both regimens of RD heparin and the warfarin were equally safe. RD heparin does not req uire daily adjustments of the dose or laboratory monitoring, which mak es it easier to administer than warfarin.