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Thromb Haemost 1997; 77(01): 032-038
DOI: 10.1055/s-0038-1655902
Clinical Studies
Schattauer GmbH Stuttgart

Efficacy and Safety of Low Molecular Weight Heparin (Ardeparin Sodium) Compared to Warfarin for the Prevention of Venous Thromboembolism after Total Knee Replacement Surgery: A Double-blind, Dose-ranging Study

John A Heit
1   The Division of Cardiovascular Diseases and Section of Hematology Research, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
,
Scott D Berkowitz
2   Divisions of Hematology and Cardiology, Duke University, Durham, North Carolina
,
Robert Bona
3   Hematology-Oncology Division, St. Francis Hospital and Medical Center, Hartford, Connecticut
,
Victor Cabanas
4   Franciscan Health System of Cincinnati, Inc., Cincinnati, Ohio
,
John D Corson
5   Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa
,
C Gregory Elliott
6   Pulmonary Division, University of Utah School of Medicine, Salt Lake City, Utah
,
Roger Lyons
7   Hematology & Oncology Associates of Texas, San Antonio, Texas, USA
,
(Ardeparin Arthroplasty Study Group) › Institutsangaben
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Publikationsverlauf

Received 11. Juni 1996

Accepted after resubmisssion 28. August 1996

Publikationsdatum:
11. Juli 2018 (online)

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Summary

We performed a double-blind, randomized clinical trial to compare the efficacy and safety of three different subcutaneous (SC) low molecular weight heparin doses (ardeparin sodium 25,35, or 50 anti-XaU/kg twice daily [BID]) to adjusted-dose warfarin (international normalized ratio [INR] = 2.0 to 3.0), as venous thromboembolism prophylaxis after total knee replacement surgery. The primary endpoint was total venous thromboembolism prevalence, defined as deep vein thrombosis discovered at postoperative venography of the operated leg, or symptomatic, objectively-documented pulmonary embolism. Of 860 patients randomized, 680 (79%) had an evaluable venogram or pulmonary embolism. The total venous thromboembolism prevalence was significantly greater among patients prophylaxed with warfarin compared to ardeparin 50 BID (38% vs 27%, p = 0.019); the prevalence among ardeparin 25 BID (37%) and 35 BID (28%) patients was similar to warfarin and ardeparin 50 BID patients, respectively. Overt bleeding occurred in 22 (7.9%) ardeparin 50 BID patients compared to 12 (4.4%) warfarin patients (p = 0.08), and in seven ardeparin 25 and 35 BID patients each (5.2% and 5.0%, respectively). Compared to the warfarin group, blood loss was significantly greater in the ardeparin 50 and 25 BID groups, and not different in the ardeparin 35 BID group.

Conclusions: Postoperative, unmonitored, fixed-dose ardeparin 50 anti-Xa U/kg SC BID is significantly more effective than adjusted-dose warfarin for this indication. Although overt bleeding among warfarin and ardeparin 50 BID patients did not differ significantly, ardeparin 50 BID patients had significantly greater blood loss. Ardeparin 35 anti-Xa U/kg SC BID may provide efficacy similar to ardeparin 50 anti-Xa U/kg SC BID but with reduced bleeding.

*For a list of investigators, see the Appendix


 

  • References

  • 1 Cohen SH, Erhlich GE, Kauffman MS, Cope C. Thrombophlebitis following knee surgery. J Bone Joint Surg 1973; 55-A: 106-112
    PubMedGoogle Scholar
  • 2 Stulberg BN, Insall JN, Williams GW, Ghelman B. Deep-vein thrombosis following total knee replasement. An analysis of six hundred and thirty-eight arthroplasties. J Bone Joint Surg 1984; 66-A: 194-201
    PubMedGoogle Scholar
  • 3 Lynch AF, Bourne RB, Rorabeck CH, Rankin RN, Conald A. Deep vein thrombosis and continuous passive motion after total knee arthroplasty. J Bone Joint Surg 1988; 70 A 11-14
    CrossrefPubMedGoogle Scholar
  • 4 Stringer MD, Steadman CA, Hedges AR, Thomas EM, Morley TR, Kakkar VV. Deep vein thrombosis after elective knee surgery. J Bone Joint Surg 1989; 71-B: 492-497
    CrossrefPubMedGoogle Scholar
  • 5 Khaw FM, Moran CG, Pinder IM, Smith SR. The incidence of fatal pulmonary embolism after knee replacement with no prophylactic anticoagulation. J Bone Joint Surg 1993; 75-B: 940-941
    CrossrefPubMedGoogle Scholar
  • 6 Mohr DN, Silverstein MD, Ilstrup DM, Heit JA, Money BF. Venous thromboembolism associated with hip and knee arthroplasty: current prophylactic practices and outcomes. Mayo Clin Proc 1992; 67: 861-870
    CrossrefPubMedGoogle Scholar
  • 7 National Institutes of Health Consensus Development Conference Statement. Prevention of venous thrombosis and pulmonary embolism. JAMA 1986; 256: 744
    CrossrefPubMedGoogle Scholar
  • 8 Clagett TP, Anderson Jr FA, Levine MN, Salzman EW, Wheeler HB. Prevention of venous thromboembolism. Chest 1992; 102 (Suppl) 391S-407S
    CrossrefPubMedGoogle Scholar
  • 9 Clagett TP, Anderson Jr FA, Heit JA, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest 1995; 108 (Suppl) 312S-314S
    CrossrefPubMedGoogle Scholar
  • 10 Paiment GD. Practice patterns in prophylaxis of deep vein thrombosis among U. S. orthopedic surgeons. Orthopedics 1994; 17: 11-13
    PubMedGoogle Scholar
  • 11 The RD Heparin Arthroplasty Group. RD heparin compared to warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. J Bone Joint Surg 1994; 76-A: 1174-1185
    PubMedGoogle Scholar
  • 12 Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134-144
    CrossrefPubMedGoogle Scholar
  • 13 The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990; 263: 2753-2759
    CrossrefPubMedGoogle Scholar
  • 14 Hull R, Raskob B, Pineo G, Rosenbloom D, Evans W, Mallory T, Anquist K, Smith F, Hughes G, Green D, Elliott CG, Panju A, Brant R. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med 1993; 329: 1370-1376
    CrossrefPubMedGoogle Scholar
  • 15 Leclerc JR, Geerts WH, Desjardins L, Laflamme GH, l'Esperance B, Demers C, Kassis J, Cruikshank M, Whitman L, Delorme F. Prevention of venous thromboembolism after knee arthroplasty – a randomized, doubleblind trial, comparing enoxaparin with warfarin. Ann Intern Med 1996; 124: 619-626
    CrossrefPubMedGoogle Scholar
  • 16 Spiro TE, Fitzgerald RH, Trowbridge AA, Overdyke WL, Gardiner GA, Young TR, Ohar JA, Gustilo RB, Whitsett TL. Enoxaparin a low molecular weight heparin and warfarin for the prevention of venous thromboembolic disease after elective knee replacement surgery. Blood 1994; 84: 246a
    PubMedGoogle Scholar
  • 17 Arcelus JI, Caprini JA, Traverso Cl. Venous thromboembolism after hospital discharge. Sem in Thromb Hemost 1993; 19 (Suppl) 142-146
    PubMedGoogle Scholar
  • 18 Trowbridge A, Bosese CK, Woodruff B, Brindley HH, Lowry WE, Spiro TE. Incidence of posthospitalization proximal deep venous thrombosis after total hip arthroplasty; a pilot study. Clin Orthop 1994; 299: 203-208
    PubMedGoogle Scholar