Subcutaneous Low-Molecular-Weight Heparin Fragmin Versus Intravenous Unfractionated Heparin in the Treatment of Acute Non Massive Pulmonary Embolism: An Open Randomized Pilot Study

Summary

Low-molecular-weight heparins have been extensively investigated in the treatment of deep venous thrombosis but limited data are available concerning their use in pulmonary embolism. In an open, pilot, randomized study, we compare the safety and efficacy of Fragmin, a low-molecular-weight heparin with those of unfractionated heparin in 60 patients with non massive pulmonary embolism (Miller Index < 20). Thirty one patients received unfractionated heparin intravenously and 29 received a fixed dose of 120 Anti-Xa IU/kg of Fragmin administered subcutaneously twice a day for 10 days. There was no pulmonary embolism recurrence nor major bleeding in either group during the treatment period. The decrease in pulmonary vascular obstruction on perfusion lung scan between day 0 and day 10 was 17 ± 13% in the Fragmin group and 16 ± 13% in the heparin group (NS). These results indicate that Fragmin may be a safe and effective treatment of submassive pulmonary embolism.

• References

• 1 Hirsh J, Fuster V. Guide to anticoagulant therapy. Part I: Heparin. American Heart Association Circulation 1994; 89: 1449-1468
• 2 Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1992; 102 suppl 408S-425S
• 3 Dalen JE, Hirsh J. American College of Chest Physicians and the National Heart, Lung and Blood Institute-National conference on antithrombotic therapy. Arch Intern Med 1986; 146: 462-472
• 4 Kelton JG, Hirsh J. Bleeding associated with antithrombotic therapy. Semin Heniatol 1980; 17: 259-295
• 5 Bratt G, Törnebohm E, Granqvist S, Aberg W, Lockner D. A comparison between low-molecular-weight heparin (Kabi 2165) and standard heparin in the intravenous treatment of deep venous thrombosis. Thromb Haemost 1985; 54: 813-817
• 6 Holm HA, Ly B, Handeland GE, Abildgaard U, Arnesen KE, Gottschalk P, Hoeg V, Aandahl M, Haugen K, Loerum F, Scheel B, Sortland O, Vinje B. Subcutaneous heparin treatment of deep venous thrombosis. A comparison of unfractionated and low-molecular-weight heparin Haemostasis 1986; 16 suppl (Suppl. 02) 30-37
• 7 Albada J, Nieuwenhuis HK, Sixma JJ. Treatment of acute venous thromboembolism with low-molecular-weight heparin (Fragmin): Results of a double-blind randomized study. Circulation 1989; 80: 935-940
• 8 Haddeland GF, Abildgaard U, Holm HA, Arnesen KE. Dose-adjusted heparin treatment of deep venous thrombosis : A comparison of unfractionated and low-molecular-weight heparin. Eur J Clin Pharmacol 1990; 39: 107-112
• 9 Prandoni P, Vigo M, Cattelan AM, Ruol A. Treatment of deep venous thrombosis by fixed doses of a low-molecular-weight heparin (CY 216). Haemostasis 1990; 20 suppl (Suppl. 01) 220-223
• 10 Bratt G, Aberg W, Johansson M, Törnebohm E, Granqvist S, Loekner D. Two daily subcutaneous injections of Fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT). Thromb Haemost 1990; 64: 506-510
• 11 Duroux P. A randomized trial of subcutaneous low-molecular-weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis : A collaborative european mullieenter study. Thromb Haemost 1991; 65: 251-256
• 12 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Brettell HR, Norton J, Carter CJ, George R, Merli G, Ward J, Mayo W, Koscnhloom D, Brant R. Subcutanenous low-molecular-weight heparin compared with continous intravenous heparin in the treatment of proximal vein thrombosis. N Engl J Med 1992; 326: 975-982
• 13 Simonneau G, Charbonnier B, Decousus H, Planchon B, Ninet J, Sié P, Silsiguen M, Combe S. Subcutaneous low-molecular-weight heparin compared with continous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis. Arch Intern Med 1993; 153: 1541-1546
• 14 Théry C, Simonneau G, Meyer G, Hélénon O, Bridey F, Armagnae C, d’Azémar P, Coquart JP. Randomized trial of subcutaneous low-molecular-weight heparin CY 216 (Fraxiparine) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism. A dose-ranging study Circulation 1992; 85: 1380-1389
• 15 Miller GA H, Sutton GC, Kerr IH, Gibson RV, Honey M. Comparison of streptokinase and heparin in treatment of isolated acute massive pulmonary embolism. Br Med J 1971; 2: 681-684
• 16 Meyer G, Collignon AM, Guinet F, Jeffrey AA, Barritault L, Sors H. Comparison of perfusion lung scanning and angiography in the estimation of vascular obstruction in acute pulmonary embolism. Eur J Nucl Med 1990; 17: 315-319
• 17 Hirsh J. Heparin. N Engl J Med 1991; 324: 1565-1574
• 18 Hirsh J. Low molecular weight heparin. Thromb Haemost 1993; 70: 204-207
• 19 Leizorovicz A, Simonneau G, Decousus H, Boissel JP. Comparison of the efficacy and safety of low molecular weight heparins and unfractionated heparin in the initial treatment of deep venous thrombosis: a meta-analysis. Br Med J 1994; 309: 299-304
• 20 Green D, Hirsh J, Heit J, Prins M, Davidson B, Lensing AW A. Low Molecular Weight Heparin: A Critical Analysis of Clinical Trials. Pharmacol Rev 1994; 46: 89-109