(Circulation. 1996;94:911-921.)
© 1996 American Heart Association, Inc.
Articles |
Hirudin in Acute Myocardial Infarction
Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B Trial
the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
Correspondence to Elliott M. Antman, MD, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
Background The TIMI 9 trial evaluated whether the direct antithrombin hirudin is more effective than an indirect-acting antithrombin, heparin, as adjunctive therapy for thrombolysis in myocardial infarction.
Methods and Results Patients (n=3002) with acute myocardial infarction were treated with aspirin and either accelerated-dose tissue plasminogen activator (TPA) or streptokinase. They were randomized within 12 hours of symptoms to receive either intravenous heparin (5000 U bolus followed by infusion of 1000 U/h) or hirudin (0.1 mg/kg bolus followed by infusion of 0.1 mg/kg per hour). The infusions of both antithrombins were titrated to a target activated partial thromboplastin time (aPTT) of 55 to 85 seconds and were administered for 96 hours. Patients randomized to hirudin were significantly more likely to have an aPTT measurement in the target range (P<.0001). The primary end point (death, recurrent nonfatal myocardial infarction, or development of severe congestive heart failure or cardiogenic shock by 30 days) occurred in 11.9% of the 1491 patients in the heparin group and 12.9% of the 1511 patients in the hirudin group (P=NS). Subgroup analyses did not reveal any profile of patients who benefited more from one of the antithrombins. The rate of major hemorrhage was similar in the heparin (5.3%) and hirudin (4.6%) groups; intracranial hemorrhage occurred in 0.9% of the heparin and 0.4% of the hirudin patients.
Conclusions Heparin and hirudin have an equal effect as adjunctive therapy to TPA and streptokinase in preventing unsatisfactory outcome in patients with acute myocardial infarction. Similar rates of major bleeding were observed for patients in the heparin and hirudin groups.
Key Words: heparin • thrombolysis • myocardial infarction
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|
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|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
H. Van Aken, C. Bode, H. Darius, C. Diehm, A. Encke, D. C. Gulba, S. Haas, W. Hacke, W. Puhl, M. Quante, et al. State-of-the-Art Review: Anticoagulation: The Present and Future Clinical and Applied Thrombosis/Hemostasis, July 1, 2001; 7(3): 195 - 204. [Abstract] [PDF]
|
|
|
|
|
|
J. Hirsh, S. S. Anand, J. L. Halperin, and V. Fuster Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association Arterioscler Thromb Vasc Biol, July 1, 2001; 21 (7): e9 - e9. [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. G. Turpie and E. M. Antman Low-Molecular-Weight Heparins in the Treatment of Acute Coronary Syndromes Arch Intern Med, June 25, 2001; 161(12): 1484 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hirsh, S. S. Anand, J. L. Halperin, and V. Fuster Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association Circulation, June 19, 2001; 103(24): 2994 - 3018. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Antman The Search for Replacements for Unfractionated Heparin Circulation, May 8, 2001; 103(18): 2310 - 2314. [Full Text] [PDF]
|
|
|
|
|
|
G. N. Levine, M. N. Ali, and A. I. Schafer Antithrombotic Therapy in Patients With Acute Coronary Syndromes Arch Intern Med, April 9, 2001; 161(7): 937 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Bahit, E. J. Topol, R. M. Califf, P. W. Armstrong, D. A. Criger, V. Hasselblad, A. Betriu, J. Hirsh, D. Ardissino, and C. B. Granger Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb J. Am. Coll. Cardiol., March 15, 2001; 37(4): 1001 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Greinacher and N. Lubenow Recombinant Hirudin in Clinical Practice : Focus on Lepirudin Circulation, March 13, 2001; 103(10): 1479 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Armstrong, C. Granger, and F. Van de Werf Bolus Fibrinolysis : Risk, Benefit, and Opportunities Circulation, February 27, 2001; 103(8): 1171 - 1173. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
J. Hirsh, T. E. Warkentin, S. G. Shaughnessy, S. S. Anand, J. L. Halperin, R. Raschke, C. Granger, E. M. Ohman, and J. E. Dalen Heparin and Low-Molecular-Weight Heparin Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety Chest, January 1, 2001; 119 (2009): 64S - 94S. [Full Text] [PDF]
|
|
|
|
|
|
J. I. Weitz and J. Hirsh New Anticoagulant Drugs Chest, January 1, 2001; 119 (2009): 95S - 107S. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Cairns, P. Theroux, H. D. Lewis Jr., M. Ezekowitz, and T. W. Meade Antithrombotic Agents in Coronary Artery Disease Chest, January 1, 2001; 119 (2009): 228S - 252S. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Ohman, R. A. Harrington, C. P. Cannon, G. Agnelli, J. A. Cairns, and J.W. Kennedy Intravenous Thrombolysis in Acute Myocardial Infarction Chest, January 1, 2001; 119 (2009): 253S - 277S. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
T. Pernerstorfer, U. Hollenstein, J.-B. Hansen, P. Stohlawetz, H.-G. Eichler, S. Handler, W. Speiser, and B. Jilma Lepirudin blunts endotoxin-induced coagulation activation Blood, March 1, 2000; 95(5): 1729 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. McRedmond, P. Harriott, B. Walker, and D. J. Fitzgerald Streptokinase-induced platelet activation involves antistreptokinase antibodies and cleavage of protease-activated receptor-1 Blood, February 15, 2000; 95(4): 1301 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. Kong, E. J. Topol, J. A. Bittl, H. D. White, P. Theroux, V. Hasselblad, and R. M. Califf Clinical Outcomes of Bivalirudin for Ischemic Heart Disease Circulation, November 16, 1999; 100(20): 2049 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Oldgren, R. Linder, L. Grip, A. Siegbahn, and L. Wallentin Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease Eur. Heart J., November 2, 1999; 20(22): 1657 - 1666. [Abstract] [PDF]
|
|
|
|
|
|
C. P. Cannon Overcoming thrombolytic resistance: Rationale and initial clinical experience combining thrombolytic therapy and glycoprotein IIb/IIIa receptor inhibition for acute myocardial infarction J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1395 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Antman, C. H. McCabe, E. P. Gurfinkel, A. G. G. Turpie, P. J. L. M. Bernink, D. Salein, A. Bayes de Luna, K. Fox, J.-M. Lablanche, D. Radley, et al. Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non-Q-Wave Myocardial Infarction : Results of the Thrombolysis In Myocardial Infarction (TIMI) 11B Trial Circulation, October 12, 1999; 100(15): 1593 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Antman, M. Cohen, D. Radley, C. McCabe, J. Rush, J. Premmereur, and E. Braunwald Assessment of the Treatment Effect of Enoxaparin for Unstable Angina/Non-Q-Wave Myocardial Infarction : TIMI 11B-ESSENCE Meta-Analysis Circulation, October 12, 1999; 100(15): 1602 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-L. Neuhaus, G. P. Molhoek, U. Zeymer, U. Tebbe, K. Wegscheider, R. Schroder, A. Camez, G. J. Laarman, G. M. Grollier, D. J. A. Lok, et al. Recombinant hirudin (lepirudin) for the improvement of thrombolysis with streptokinase in patients with acute myocardial infarction: Results of the HIT-4 trial J. Am. Coll. Cardiol., October 1, 1999; 34(4): 966 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Zed, J. E. Tisdale, and S. Borzak Low-Molecular-Weight Heparins in the Management of Acute Coronary Syndromes Arch Intern Med, September 13, 1999; 159(16): 1849 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
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J. J. Cook, S. J. Gardell, M. A. Holahan, G. R. Sitko, G. L. Stump, A. A. Wallace, D. B. Gilberto, T. R. Hare, J. A. Krueger, D. L. Dyer, et al. Antithrombotic Efficacy of Thrombin Inhibitor L-374,087: Intravenous Activity in a Primate Model of Venous Thrombus Extension and Oral Activity in a Canine Model of Primary Venous and Coronary Artery Thrombosis J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 503 - 510. [Abstract] [Full Text]
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G. Frostfeldt, G. Ahlberg, G. Gustafsson, G. Helmius, B. Lindahl, A. Nygren, A. Siegbahn, E. Swahn, P. Venge, and L. Wallentin Low molecular weight heparin (dalteparin) as adjuvant treatment to thrombolysis in acute myocardial infarction--a pilot study: Biochemical Markers in Acute Coronary Syndromes (BIOMACS II) J. Am. Coll. Cardiol., March 1, 1999; 33(3): 627 - 633. [Abstract] [Full Text] [PDF]
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C. P. Cannon, J. Dingemanse, C. H. Kleinbloesem, T. Jannett, K. M. Curry, and C. P. Valcke Automated Heparin-Delivery System to Control Activated Partial Thromboplastin Time : Evaluation in Normal Volunteers Circulation, February 16, 1999; 99(6): 751 - 756. [Abstract] [Full Text] [PDF]
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R. C. Becker, J. S. Hochman, C. P. Cannon, F. A. Spencer, S. P. Ball, M. J. Rizzo, E. M. Antman, and for the TIMI 9 Investigators Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists: Observations from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9 Study J. Am. Coll. Cardiol., February 1, 1999; 33(2): 479 - 487. [Abstract] [Full Text] [PDF]
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S. M. Bates and J. I. Weitz Prevention of activation of blood coagulation during acute coronary ischemic syndromes: beyond aspirin and heparin Cardiovasc Res, February 1, 1999; 41(2): 418 - 432. [Abstract] [Full Text] [PDF]
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C. P. Cannon, C. M. Gibson, C. H. McCabe, A. A. J. Adgey, M. J. Schweiger, R. F. Sequeira, G. Grollier, R. P. Giugliano, M. Frey, H. S. Mueller, et al. TNK–Tissue Plasminogen Activator Compared With Front-Loaded Alteplase in Acute Myocardial Infarction : Results of the TIMI 10B Trial Circulation, December 22, 1998; 98(25): 2805 - 2814. [Abstract] [Full Text] [PDF]
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 N. R Grubb, P. Bloomfield, and C. A Ludlam The end of the heparin pump? BMJ, December 5, 1998; 317(7172): 1540 - 1542. [Full Text]
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The Paradigm Investigators Combining thrombolysis with the platelet glycoprotein IIb/IIIa inhibitor lamifiban: results of the Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) Trial J. Am. Coll. Cardiol., December 1, 1998; 32(7): 2003 - 2010. [Abstract] [Full Text] [PDF]
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 V. Fuster, J. J. Badimon, and J. H Chesebro Atherothrombosis: mechanisms and clinical therapeutic approaches Vascular Medicine, August 1, 1998; 3(3): 231 - 239. [Abstract] [PDF]
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R. A. Kloner, T. Shook, E. M. Antman, C. P. Cannon, K. Przyklenk, K. Yoo, C. H. McCabe, and E. Braunwald Prospective Temporal Analysis of the Onset of Preinfarction Angina Versus Outcome : An Ancillary Study in TIMI-9B Circulation, March 24, 1998; 97(11): 1042 - 1045. [Abstract] [Full Text] [PDF]
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C. P. Cannon, C. H. McCabe, S. Borzak, T. D. Henry, M. D. Tischler, H. S. Mueller, R. Feldman, S. T. Palmeri, K. Ault, S. A. Hamilton, et al. Randomized Trial of an Oral Platelet Glycoprotein IIb/IIIa Antagonist, Sibrafiban, in Patients After an Acute Coronary Syndrome : Results of the TIMI 12 Trial Circulation, February 3, 1998; 97(4): 340 - 349. [Abstract] [Full Text] [PDF]
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R. Altman Controversies in Antithrombotic Therapy in Cardiovascular Diseases Clinical and Applied Thrombosis/Hemostasis, January 1, 1998; 4(1): 11 - 24. [Abstract] [PDF]
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H. D. White, P. E. Aylward, M. J. Frey, A. A. J. Adgey, R. Nair, W. S. Hillis, Y. Shalev, M. A. Brown, J. K. French, R. Collins, et al. Randomized, Double-blind Comparison of Hirulog Versus Heparin in Patients Receiving Streptokinase and Aspirin for Acute Myocardial Infarction (HERO) Circulation, October 7, 1997; 96(7): 2155 - 2161. [Abstract] [Full Text]
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M. Cohen, C. Demers, E. P. Gurfinkel, A. G.G. Turpie, G. J. Fromell, S. Goodman, A. Langer, R. M. Califf, K. A.A. Fox, J. Premmereur, et al. A Comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Unstable Coronary Artery Disease N. Engl. J. Med., August 14, 1997; 337(7): 447 - 452. [Abstract] [Full Text] [PDF]
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J. M. Gore and J. E. Dalen Cardiovascular Disease JAMA, June 18, 1997; 277(23): 1845 - 1846. [PDF]
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C. Bode, S. R. Hanson, J. F. Schmedtje, E. Haber, P. Mehwald, A. B. Kelly, L. A. Harker, and M. S. Runge Antithrombotic Potency of Hirudin Is Increased in Nonhuman Primates by Fibrin Targeting Circulation, February 18, 1997; 95(4): 800 - 804. [Abstract] [Full Text]
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C. P. Cannon, C. H. McCabe, C. M. Gibson, M. Ghali, R. F. Sequeira, G. R. McKendall, J. Breed, N. B. Modi, N. L. Fox, R. P. Tracy, et al. TNK-Tissue Plasminogen Activator in Acute Myocardial Infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A Dose-Ranging Trial Circulation, January 21, 1997; 95(2): 351 - 356. [Abstract] [Full Text]
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J. Loscalzo Thrombin Inhibitors in Fibrinolysis: A Hobson's Choice of Alternatives Circulation, September 1, 1996; 94(5): 863 - 865. [Full Text]
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E. M. Antman, H. W. Louwerenburg, H. F. Baars, J. C.L. Wesdorp, B. Hamer, J.-P. Bassand, F. Bigonzi, G. Pisapia, C. M. Gibson, H. Heidbuchel, et al. Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction: Results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial Circulation, April 9, 2002; 105(14): 1642 - 1649. [Abstract] [Full Text] [PDF]
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