Ardeparin Sodium for Extended Out-of-Hospital Prophylaxis against Venous Thromboembolism after Total Hip or Knee Replacement

Abstract

The optimal duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain. To determine the efficacy and safety of extended out-of-hospital prophylaxis with low-molecular-weight heparin (ardeparin sodium). Randomized, double-blind, placebo-controlled trial. 33 community, university, or university-affiliated hospitals. 1195 adults who had elective total hip or knee replacement and completed 4 to 10 days of postoperative ardeparin prophylaxis. Daily subcutaneous ardeparin (100 anti-Xa IU/kg of body weight) or placebo from time of hospital discharge to 6 weeks after surgery. Symptomatic, objectively documented venous thromboembolism or death, along with major bleeding, from time of hospital discharge to 12 weeks after surgery. Patients who received ardeparin (n = 607) and those who received placebo (n = 588) did not differ significantly in the cumulative incidence of venous thromboembolism or death (9 cases [1.5%] compared with 12 cases [2.0%]; odds ratio, 0.7 [95% CI, 0.3 to 1.7]; P > 0.2; absolute difference, -0.56 percentage points [CI, -2.2 to 1.1 percentage points]) or major bleeding (2 cases [0.3%] compared with 3 cases [0.5%]). Among patients who had total knee or total hip replacement and received 4 to 10 days of postoperative ardeparin prophylaxis, the cumulative incidence of symptomatic venous thromboembolism or death after hospital discharge was not significantly reduced by extended out-of-hospital ardeparin prophylaxis. Extended ardeparin use could provide a maximum 2.2-percentage point true reduction in such events. The benefit of extended ardeparin use is not clinically important for most patients. Future research should identify high-risk patients who would benefit most from extended prophylaxis.