| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1997;96:2155-2161.)
© 1997 American Heart Association, Inc.
Articles |
Randomized, Double-blind Comparison of Hirulog Versus Heparin in Patients Receiving Streptokinase and Aspirin for Acute Myocardial Infarction (HERO)
From Green Lane Hospital (H.D.W., J.K.F.), Auckland, New Zealand; Flinders Cardiovascular Centre (P.E.A.), Adelaide, South Australia; Heart Center of Sarasota (M.J.F.), Fla; Royal Victoria Hospital (A.A.J.A.), Belfast, Northern Ireland; University Hospital of Cleveland (R.N.), Ohio; Western Infirmary (W.S.H.), Glasgow, Scotland; Sinai Samaritan Medical Center (Y.S.), Milwaukee, Wis; Royal Adelaide Hospital (M.A.B.), South Australia; Radcliffe Infirmary (R.C.), Oxford, England; and Biogen Inc (J.M., B.A.), Boston, Mass.
Correspondence to Professor Harvey White, Cardiology Department, Green Lane Hospital, Private Bag 92 189, Auckland 1030, New Zealand. E-mail white002{at}msn.com
Background Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates.
Methods and Results Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg · kg-1 · h-1 for 12 hours then 0.125 mg · kg-1 · h-1), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg · kg-1 · h-1 for 12 hours then 0.25 mg · kg-1 · h-1). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog, P=.023; heparin versus high-dose hirulog, P=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P<.01).
Conclusions Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.
Key Words: myocardial infarction • heparin • hirulog • streptokinase
This article has been cited by other articles:
 |
|
 |
|
  S. Schulman, R. J. Beyth, C. Kearon, and M. N. Levine Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 257S - 298S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Goodman, V. Menon, C. P. Cannon, G. Steg, E. M. Ohman, and R. A. Harrington Acute ST-Segment Elevation Myocardial Infarction: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 708S - 775S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Singh, J. Molnar, and R. Arora Efficacy and Safety of Bivalirudin Versus Heparins in Reduction of Cardiac Outcomes in Acute Coronary Syndrome and Percutaneous Coronary Interventions Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2007; 12(4): 283 - 291. [Abstract] [PDF]
|
|
|
|
 |
|
 P. R. Sinnaeve, J. Simes, S. Yusuf, J. Garg, S. Mehta, J. Eikelboom, J. A. Bittl, P. Serruys, E. J. Topol, and C. B. Granger Direct thrombin inhibitors in acute coronary syndromes: effect in patients undergoing early percutaneous coronary intervention Eur. Heart J., November 2, 2005; 26(22): 2396 - 2403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Menon, R. A. Harrington, J. S. Hochman, C. P. Cannon, S. D. Goodman, R. G. Wilcox, H. J. Schunemann, and E. M. Ohman Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 549S - 575S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Eichler, N. Lubenow, U. Strobel, and A. Greinacher Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin Blood, January 15, 2004; 103(2): 613 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Eikelboom, H. White, and S. Yusuf The evolving role of direct thrombin inhibitors in acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 70S - 78S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The Task Force on the Management of Acute Myocardi, F. Van de Werf, D. Ardissino, A. Betriu, D. V. Cokkinos, E. Falk, K. A.A. Fox, D. Julian, M. Lengyel, F.-J. Neumann, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation Eur. Heart J., January 1, 2003; 24(1): 28 - 66. [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. Baker Jr Thrombolytic Therapy Clinical and Applied Thrombosis/Hemostasis, October 1, 2002; 8(4): 291 - 314. [PDF]
|
|
|
|
|
|
C.-K. Wong, J.K. French, M.W. Krucoff, W. Gao, P.E. Aylward, and H.D. White Slowed ST segment recovery despite early infarct artery patency in patients with Q waves at presentation with a first acute myocardial infarction. Implications of initial Q waves on myocyte reperfusion Eur. Heart J., September 2, 2002; 23(18): 1449 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-K. Wong, J.K. French, J. Andrews, M.J. Frey, A.A.J. Adgey, P.E. Aylward, and H.D. White Usefulness of the presenting electrocardiogram in predicting myocardial salvage with thrombolytic therapy in patients with a first acute myocardial infarction Eur. Heart J., March 1, 2002; 23(5): 399 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Armstrong and D. Collen Fibrinolysis for Acute Myocardial Infarction : Current Status and New Horizons for Pharmacological Reperfusion, Part 2 Circulation, June 19, 2001; 103(24): 2987 - 2992. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. I. Weitz and J. Hirsh New Anticoagulant Drugs Chest, January 1, 2001; 119(1_suppl): 95S - 107S. [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(1_suppl): 253S - 277S. [Full Text] [PDF]
|
|
|
|
|
|
H.D. White Cardiogenic shock: a more aggressive approach is now warranted Eur. Heart J., December 1, 2000; 21(23): 1897 - 1901. [PDF]
|
|
|
|
|
|
P.W. Armstrong Reperfusion synergism: will it be both sustained and safe? Eur. Heart J., December 1, 2000; 21(23): 1913 - 1916. [PDF]
|
|
|
|
|
|
N. S. Van de Water, J. K. French, M. Lund, T. A. Hyde, H. D. White, and P. J. Browett Prevalence of factor v leiden and prothrombin variant g20210a in patients age <50 years with no significant stenoses at angiography three to four weeks after myocardial infarction J. Am. Coll. Cardiol., September 1, 2000; 36(3): 717 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Andrews, I. T. Straznicky, J. K. French, C. L. Green, A. C. P. Maas, M. Lund, M. W. Krucoff, and H. D. White ST-Segment Recovery Adds to the Assessment of TIMI 2 and 3 Flow in Predicting Infarct Wall Motion After Thrombolytic Therapy Circulation, May 9, 2000; 101(18): 2138 - 2143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. French, T. A. Hyde, I. T. Straznicky, J. Andrews, M. Lund, D. J. Amos, A. Zambanini, C. J. Ellis, B. J. Webber, S. C. McLaughlin, et al. Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1516 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Iqbal, H. Messmore, D. Hoppensteadt, J. Fareed, and W. Wehrmacher State-of-the-Art Review : Thrombolytic Drugs in Acute Myocardial Infarction Clinical and Applied Thrombosis/Hemostasis, January 1, 2000; 6(1): 1 - 13. [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]
|
|
|
|
|
|
P. Klement, P. Liao, and L. Bajzar A Novel Approach to Arterial Thrombolysis Blood, October 15, 1999; 94(8): 2735 - 2743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Song, G. Huhle, L. Wang, U. Hoffmann, and J. Harenberg Generation of Anti-Hirudin Antibodies in Heparin-Induced Thrombocytopenic Patients Treated With R-Hirudin Circulation, October 5, 1999; 100(14): 1528 - 1532. [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]
|
|
|
|
|
|
J. K. French, T. A. Hyde, H. Patel, D. J. Amos, S. C. McLaughlin, B. J. Webber, and H. D. White Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks J. Am. Coll. Cardiol., July 1, 1999; 34(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I.-K. Jang, D. F. M. Brown, R. P. Giugliano, H. V. Anderson, D. Losordo, J. C. Nicolau, O. P. Dutra, O. Bazzino, V. M. Viamonte, R. Norbady, et al. A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with Novastan and TPA (MINT) study J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1879 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J K French, I T Straznicky, B J Webber, P E Aylward, M J Frey, A A J Adgey, B F Williams, S C McLaughlin, and H D White Angiographic frame counts 90 minutes after streptokinase predict left ventricular function at 48 hours following myocardial infarction Heart, February 1, 1999; 81(2): 128 - 133. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. E. Gutstein and V. Fuster Pathophysiology and clinical significance of atherosclerotic plaque rupture Cardiovasc Res, February 1, 1999; 41(2): 323 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. A. Baughman, S. C. Kapoor, R. K. Agarwal, J. Kisicki, F. Catella-Lawson, and G. A. FitzGerald Oral Delivery of Anticoagulant Doses of Heparin : A Randomized, Double-Blind, Controlled Study in Humans Circulation, October 20, 1998; 98(16): 1610 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fareed Antithrombin Agents as Anticoagulants and Antithrombotics: Implications in Drug Development Clinical and Applied Thrombosis/Hemostasis, October 1, 1998; 4(4): 227 - 237. [Abstract] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
J. H. Chesebro Direct Thrombin Inhibition Superior to Heparin During and After Thrombolysis : Dose, Duration, and Drug Circulation, October 7, 1997; 96(7): 2118 - 2120. [Full Text]
|
|