Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: The optimal duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain.

OBJECTIVE: To determine the efficacy and safety of extended out-of-hospital prophylaxis with low-molecular-weight heparin (ardeparin sodium).

DESIGN: Randomized, double-blind, placebo-controlled trial.

SETTING: 33 community, university, or university-affiliated hospitals.

PATIENTS: 1195 adults who had elective total hip or knee replacement and completed 4 to 10 days of postoperative ardeparin prophylaxis.

INTERVENTION: Daily subcutaneous ardeparin (100 anti-Xa IU/kg of body weight) or placebo from time of hospital discharge to 6 weeks after surgery.

MEASUREMENTS: Symptomatic, objectively documented venous thromboembolism or death, along with major bleeding, from time of hospital discharge to 12 weeks after surgery.

RESULTS: 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%]).

CONCLUSIONS: 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.