Current issues of ACP Journal Club are published in Annals of Internal Medicine


Ardeparin plus graduated compression stockings prevented DVT after knee surgery

ACP J Club. 1996 Nov-Dec;125:63. doi:10.7326/ACPJC-1996-125-3-063

Source Citation

Levine MN, Gent M, Hirsh J, et al. Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery. Arch Intern Med. 1996 Apr 22;156:851-6. [PubMed ID: 8774203]



To compare the combination of ardeparin—a low-molecular-weight heparin (LMWH)—and graduated compression stockings (GCSs) with GCSs alone for prevention of deep venous thrombosis (DVT) in patients having major knee surgery.


Randomized, double-blind, placebo-controlled trial with 14-day follow-up.


5 hospitals in Canada.


246 patients (mean age 68 y, 60% women) who were having total knee replacement or tibial osteotomy. Exclusion criteria included age < 30 years; increased risk for bleeding or thrombosis; allergy to iodine, radiopaque dye, heparin, pork, or fish; alcohol or drug abuse; uncontrolled hypertension; requirement for aspirin therapy; bilateral knee surgery; or inability to wear stockings. Follow-up was complete.


Patients were allocated to subcutaneous ardeparin, 0.005 mL/kg of body weight (50 anti-Xa units/kg) twice daily (n = 122) or placebo (n = 124) for 14 days or until hospital discharge. Patients in both groups were fitted with GCSs below the knees immediately after wound closure.

Main outcome measures

Patients had bilateral venography before hospital discharge. Occurrence of DVT, proximal DVT, pulmonary embolism, and major bleeding.

Main results

199 patients had evaluable venograms. Of these, DVT was detected in 28 patients (29%) who received ardeparin compared with 60 patients (58%) who received placebo (P < 0.001) (Table). Proximal DVT was also reduced in patients who received ardeparin compared with those who received placebo (P < 0.001) (Table). Pulmonary embolism was confirmed in 1 patient in each group. Major hemorrhage did not differ between groups (P < 0.99) (Table).


The combination of ardeparin and graduated compression stockings reduced total and proximal deep venous thrombosis compared with stockings alone in patients having major knee surgery.

Source of funding: Wyeth-Ayerst.

For article reprint: Dr. M.N. Levine, Hamilton Regional Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2, Canada. FAX 905-389-9288.

Table. Ardeparin plus graduated compression stockings (GCSs) vs placebo plus GCSs for preventing deep venous thrombosis (DVT)*

Outcomes at 14 d Ardreparin + GCSs Placebo + GCSs RRR (95% CI) NNT (CI)
DVT 29% 58% 50% (30 to 65) 3% (2 to 6)
Proximal DVT 2% 16% 87% (50 to 97) 7% (5 to 16)
Major hemorrhage 2.5% 2.4% Not significant Not significant

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


DVT remains a substantial complication after major knee surgery despite multiple prophylactic methods. The incidence of DVT is approximately 60% if no prophylaxis is used and ranges from 11% to 79% with use of intermittent compression stockings, LMWH, low-dose heparin, warfarin, or aspirin (1). LMWHs are the newest preventive intervention, with DVT rates of 19% to 37% and proximal DVT rates of 0% to 6% (2, 3). This study by Levine and colleagues used weight-adjusted ardeparin given twice daily. The 29% incidence rate of DVT (2% proximal) is similar to that seen in another study that used enoxaparin (4), and in a previous study, ardeparin was shown to be more effective than warfarin (5).

The American College of Chest Physicians (1) recommends LMWH or intermittent compression stockings as prophylaxis during elective knee surgery. No studies have compared LMWH with intermittent compression stockings.

The high rate of distal DVT occurring with all prophylactic measures (27% in this study) raises the possibility of proximal clot propagation after discharge from the hospital. DVT outcomes were measured with bilateral venograms when ardeparin or placebo therapy was stopped at 14 days or at hospital discharge. The study would have been strengthened with longer (6 months) follow-up.

This study, along with previous studies of LMWH, confirms the effectiveness and safety of LMWH as prophylaxis against DVT in patients having knee surgery.

Scott Kaatz, DO
Henry Ford HospitalDetroit, Michigan, USA


1. Clagett GP, Anderson FA Jr, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest. 1995;108:312S-34S.

2. Lensing AW, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis. Arch Intern Med. 1995;155:601-7.

3. Nurmohamed MT, Rosendaal FR, Buller HR, et al. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet. 1992; 340:152-6.

4. Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med. 1996;124:619-26.

5. RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. RD Heparin Arthroplasty Group. J Bone Joint Surg. 1994;76A:1174-85.