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 managed with an elective total hip or total knee arthroplasty were compared with the efficacy and safety of warfarin in an open-label prospective, multicenter trial. Patients were randomized to receive either a fixed dose of fifty anti- factor-X(a) units of RD heparin per kilogram of body weight, administered subcutaneously twice daily, beginning postoperatively; a fixed dose of ninety anti-factor-X(a) units of RD heparin per kilogram of body weight, administered subcutaneously once daily, beginning postoperatively; or five milligrams of warfarin, administered orally preoperatively, followed by a daily adjusted dose of warfarin to prolong the prothrombin time ratio to 1.2 to 1.5. The primary measure of efficacy was contrast venography of the treated limb, performed by local radiologists blinded to the type of treatment that had been assigned. Nine hundred and sixty-nine patients had a complete assessment for the presence of deep-vein thrombosis. The over-all rates of venous thromboembolic disease were 16 per cent (95 per cent confidence interval, 13 to 21 per cent) (fifty-three) for the 328 patients who received RD heparin twice daily, 21 per cent (95 per cent confidence interval, 17 to 26 per cent) (sixty-eight) for the 320 patients who received RD heparin once daily, and 27 per cent (95 per cent confidence interval, 22 to 32 per cent) (eighty-seven) for the 321 patients who received warfarin (p < 0.001 for RD heparin administered twice daily compared with warfarin; p = 0.13 for RD heparin administered once daily compared 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 interval, -6 to 37 per cent), respectively. The rates of venous thromboembolic disease after 523 total hip arthroplasties were 8, 14, and 14 per cent for the patients who received RD heparin twice daily, those who received it once daily, and those who received warfarin (p = 0.07 for RD heparin administered twice daily compared with warfarin; p = 0.82 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 compared with warfarin; p = 0.04 for RD heparin administered once daily compared with warfarin). A fixed dose of fifty anti-factor-X(a) units of RD heparin per kilogram of body weight administered subcutaneously twice daily, beginning postoperatively, appeared more effective than low-dose warfarin for the prevention of venous thromboembolic disease following a major orthopaedic procedure on the lower limb. For the patients 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 daily 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 require daily adjustments of the dose or laboratory monitoring, which makes it easier to administer than warfarin.