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).


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
33 community, university, or university-affiliated hospitals.


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


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


METHODS
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.
Heit
J A
JA
Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Elliott
C G
CG
Trowbridge
A A
AA
Morrey
B F
BF
Gent
M
M
Hirsh
J
J
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D002423:Cause of Death; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011655:Pulmonary Embolism / Q000209:etiology / Q000517:prevention & control*; D013921:Thrombocytopenia / Q000139:chemically induced; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000209:etiology / Q000517:prevention & control*
D006495:Heparin, Low-Molecular-Weight; D010919:Placebos; C093450:ardeparin