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DOI: 10.1055/s-0038-1649627
Orgaran (Org 10172) or Heparin for Preventing Venous Thrombosis after Elective Surgery for Malignant Disease? A Double-Blind, Randomised, Multicentre Comparison
Publikationsverlauf
Received 18. Januar 1992
Accepted after revision 18. Mai 1993
Publikationsdatum:
24. Juli 2018 (online)
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Summary
This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units Standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. “Intent to treat” analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy (“compliant patients”) were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.
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References
- 1 Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopaedic, and urologic surgery. New Engl J Med 1988; 318: 1162-1173
- 2 Clagett GP, Reisch JS. Prevention of venous thomboembolism in general surgical patients. Results of meta-analysis. Ann Surg 1988; 208: 227-240
- 3 Strand L, Bank-Mikkelsen OK, Lindewald H. Small heparin doses as prophylaxis against deep-vein thrombosis in major surgery. Acta Chir Scand 1975; 141: 624-627
- 4 Rem J, Duckert F, Fridrich R, Gruber UF. Subkutane kleine Heparindosen zur Thromboseprophylaxe in der allgemeinen Chirurgie und Urologie. Schweiz Med Wschr 1975; 105: 827-835
- 5 Gallus AS, Hirsh J, O‗Brien EO, McBride JA, Tuttle RJ, Gent M. Prevention of venous thrombosis with small, subcutaneous doses of heparin. J Am Med Assoc 1976; 235: 1980-1982
- 6 Clarke-Pearson DL, Coleman RE, Synan IS, Hinshaw W, Creasman WT. Venous thromboembolism prophylaxis in gynecologic oncology: a prospective, controlled trial of low-dose heparin. Am J Obstet Gynecol 1983; 145: 606-613
- 7 Rogers PH, Walsh PN, Marder VJ. et al. Controlled trial of low-dose heparin and sulfinpyrazone to prevent venous thromboembolism after operation on the hip. J Bone Joint Surg 1978; 60-A: 758-762
- 8 Planes A, Vochelle N, Mazas F. et al. Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemostas 1988; 60: 407-410
- 9 Moskovitz PA, Ellenberg SS, Feffer HL. et al. Low-dose heparin in the prevention of venous thromboembolism in total hip arthroplasty and surgical repair of hip fractures. J Bone Joint Surg 1978; 60-A: 1065-1070
- 10 Chong BH. Heparin-induced thrombocytopenia. Blood Rev 1988; 2: 108-114
- 11 Hirsh J, Levine MN. Low molecular weight heparins. Blood 1992; 79: 1-17
- 12 Cade JF, Buchanan MR, Boneu B. et al. A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: the influence of the method of preparation. Thromb Res 1984; 35: 613-625
- 13 Bang CJ, Berstad A, Talstad I. Gastric mucosal bleeding after unfractionated and low molecular weight heparin in rats. Scand J Gastroenterol 1990; 25: 379-382
- 14 Cadroy Y, Harker LA, Hanson SR. Inhibition of platelet-dependent thrombosis by low molecular weight heparin (CY222): comparison with Standard heparin. J Lab Clin Med 1989; 114: 349-357
- 15 Levine MN, Hirsh J, Gent M. et al. Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 1991; 114: 545-551
- 16 Meuleman DG, Hobbelen PMJ, van Dedem G, Moelker HCT. A novel anti-thrombotic heparinoid (Org 10172) devoid of bleeding inducing capacity: a survey of its pharmacological properties in experimental animal models. Thromb Res 1982; 27: 353-363
- 17 Boneu B, Buchanan MR, Cade JF. et al. Effects of heparin, its low molecular weight fractions and other glycosaminoglycans on thrombus growth in vivo. Thromb Res 1985; 40: 81-89
- 18 Hobbelen PMJ, Vogel GMT, Meuleman DG. Time courses of the antithrombotic effects, bleeding enhancing effects and interactions with factor Xa and thrombin after administration of low molecular weight heparinoid Org 10172 or heparin to rats. Thromb Res 1987; 48: 549-558
- 19 Cade JF, Wood M, Magnani H, Westlake GW. Early clinical experience of a new heparinoid, Org 10172, in prevention of venous thrombosis. Thromb Res 1987; 45: 497-503
- 20 Kaplan AL, Meier P. Non-parametric estimation from incomplete values. J Am Stat Assoc 1958; 53: 457-481
- 21 Kalbfleisch JD, Prentice RL. (eds) The Statistical Analysis of Failure Time Data. New York: J Wiley & Sons; 1980
- 22 Rohlf FJ, Sokal RR. Statistical Tables. 2.. San Francisco: W. H. Freeman and Company; 1981
- 23 Connolly SJ, Laupacis A, Gent M. et al. Canadian atrial fibrillation anticoagulation (CAFA) study. J Am Coll Cardiol 1991; 18: 349-355
- 24 Blum A, Desruennes E, Elias A, Lagrange G, Loriferne JF. DVT prophylaxis in surgery for digestive tract cancer comparing the LMW heparinoid Org 10172 (Lomoparan) with calcium heparin. Thromb Haemostas 1989; 62 (Suppl. 00) 126
- 25 Fricker J-P, Vergnes Y, Schach R. et al. Low dose heparin versus low molecular weight heparin (Kabi 2165, Fragmin) in the prophylaxis of thromboembolic complications of abdominal oncological surgery. Eur J Clin Ivest 1988; 18: 561-567
- 26 Caen JP. A randomized double-blind study between a low molecular weight heparin Kabi 2165 and standard heparin in the prevention of deep vein thrombosis in general surgery. A French multicenter trial. Thromb Haemostas 1988; 59: 216-220
- 27 Bergqvist D, Burmark AS, Frisell J. et al. Low molecular weight heparin once daily compared with conventional low dose heparin twice daily. A prospective double-blind multicentre trial on prevention of postoperative thrombosis. Br J Surg 1986; 73: 204-208
- 28 Bergqvist D, Matzsch T, Burmark AS. et al. Low molecular weight heparin given the evening before surgery compared with conventional low dose heparin in prevention of thrombosis. Br J Surg 1988; 75: 888-891
- 29 Hartl P, Brucke P, Dienstl E, Vinazzer H. Prophylaxis of thromboembolism in general surgery: comparison between standard heparin and Fragmin. Thromb Res 1990; 57: 577-584
- 30 Bergqvist D, Burmark AS, Frisell J. et al. Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin. Semin Thromb Hemostas 1990; 16 (Suppl. 00) 19-24
- 31 Samama M, Bernard JP, Bonnardot JP, Combe-Tamzali S, Lanson Y, Tissot E. Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis. Br J Surg 1988; 75: 128-131
- 32 Kakkar VV, Murray WJG. Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thromboembolism: a co-operative study. Br J Surg 1985; 72: 786-791
- 33 Encke A, Breddin K. Comparison of low molecular weight heparin and unfractionated heparin for the prevention of deep vein throm-bosis in patients undergoing abdominal surgery. Br J Surg 1988; 75: 1058-1063
- 34 Hoek JA, Henny ChP, Knipscheer HC, ten Cate H, Nurmohammed MT, ten Cate JW. The effect of different anaesthetic techniques on the incidence of thrombosis following total hip replacement. Thromb Haemostas 1991; 65: 122-125
- 35 Hoek JA, Nurmohammed MT, Hamelynck KJ. et al. Prevention of deep vein thrombosis following total hip replacement by low molecular weight heparinoids. Thromb Haemostas 1992; 67: 28-32
- 36 Gallus AS. Anticoagulants in the prevention of venous thromboembolism. Clin Haematol 1990; 3: 651-684
- 37 Turpie AGG, Levine MN, Hirsh J. et al. Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke. Lancet 1987; i: 524-526
- 38 Turpie AGG, Gent M, Côte R. et al. A low molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study. Ann Intern Med 1992; 117: 353-357