Rh. Fitzgerald et al., Prevention of venous thromboembolic disease following primary total knee arthroplasty - A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin, J BONE-AM V, 83A(6), 2001, pp. 900-906
Ortopedics, Rehabilitation & Sport Medicine","da verificare
Background: Patients treated with total knee arthroplasty are at high risk
for the development of venous thrombo-embolism postoperatively. This study
compared the efficacy and safety of two common thromboprophylactic agents,
enoxaparin (a low-molecular-weight heparin) and warfarin.
Methods: Three hundred and forty-nine patients were included in a prospecti
ve, randomized, multicenter, open-label, parallel-group clinical trial. Tre
atment with enoxaparin (30 mg, administered subcutaneously twice daily) or
warfarin (adjusted to an international normalized ratio of 2 to 3) was init
iated during the immediate postoperative period, within eight hours after t
he surgery, and was continued for four to fourteen days. Venous thromboembo
lism was defined as deep-vein thrombosis documented by contrast venography,
symptomatic deep-vein thrombosis documented by lower-extremity ultrasonogr
aphy, or symptomatic pulmonary embolism confirmed by a positive lung scan o
r pulmonary angiography.
Results: In the all-treated-patients group, eighty (45%) of the 176 warfari
n-treated patients had venous thromboembolism: fifty-nine (34%) had distal
deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one
(0.6%), pulmonary embolism. Venous thromboembolism developed in significant
ly fewer (p = 0.0001) enox- aparin-treated patients (forty-four of 173; 25%
): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal
deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-trea
ted patients also had a significantly lower prevalence of proximal deep-vei
n thrombosis (p = 0.002). The estimated odds for the development of venous
thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3
.19) with warfarin than they were with enoxaparin. Major hemorrhage occurre
d in four warfarin-treated patients and nine enoxaparin-treated patients; w
ith the numbers available, this difference was not significant (p = 0.17).
clinically important operative-site hemorrhage occurred in six (3%) of the
warfarin-treated patients and twelve (7%) of the enoxaparin-treated patient
s (p = 0.15).
Conclusions: A fixed 30-mg subcutaneous dose of enoxaparin, administered tw
ice daily, with the first dose administered within eight hours after the co
mpletion of surgery, was significantly more effective than adjusted-dose wa
rfarin in reducing the occurrence of asymptomatic venous thromboembolism, i
ncluding proximal deep-vein thrombosis, in patients undergoing total knee a
rthroplasty. With the numbers available, there was no significant differenc
e between groups with regard to the occurrence of major hemorrhagic complic
ations; however, the rate of overall hemorrhagic complications was higher i
n the enoxaparin group.