Abstract
Thrombus formation at the site of plaque rupture has long been recognized as the inciting event in the pathophysiology of ST-segment elevation myocardial infarction (STEMI). Fibrinolysis remains the most common mode of revascularization worldwide and has the recognized limitation of creating large amounts of activated thrombin as a byproduct of its mechanism of action. Several antithrombin agents have been developed as adjuncts to either pharmacologic or mechanical revascularization strategies for this patient population. Unfractionated heparin remains a very important agent although low-molecular weight heparins and direct thrombin inhibitors have been developed and studied in these patients. How each class of antithrombin therapies will be optimally utilized for patients with STEMI remains to be defined. At the core of any antithrombin therapy rests the goals of minimizing ischemic complications while simultaneously avoiding any bleeding complications.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Yusuf S, Reddy S, Ounpuu S, Anand S (2001) Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 104:2746–2753
Keeley EC, Boura JA, Grines CL (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361:13–20
Rosenberg RD, Bauer KA (1994) The heparin-antithrombin system: a natural anticoagulant mechanism. In: Colman RW, Hirsh J, Marder VJ, Salzman EW (eds) Hemostasis and thrombosis: basic principles and clinical practice, 3rd edn. J.B. Lippincott, Philadelphia
GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (1990) Lancet 336:65–71
ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group (1992) Lancet 339:753–770
An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. N Engl J Med 1993;329:673-82.
The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. The GUSTO Angiographic Investigators (1993) N Engl J Med 329:1615–1622
Randomized factorial trial of high-dose intravenous streptokinase, of oral aspirin and of intravenous heparin in acute myocardial infarction. ISIS (International Studies of Infarct Survival) pilot study (1987) Eur Heart J 8:634–642
de Bono DP, Simoons ML, Tijssen J et al (1992) Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial. Br Heart J 67:122–128
Col J DO, Hanique G, Delligne B, Boland J, Pirenne B, Cheron P, Renkin J (1992) Infusion of heparin conjunct to streptokinase accelerates reperfusion of acute myocardial infarction: results of a double blind randomized study (OSIRIS). Circulation 86:259a
O’Connor CM, Meese R, Carney R et al (1994) A randomized trial of intravenous heparin in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex) in acute myocardial infarction: the Duke University Clinical Cardiology Study (DUCCS) 1. J Am Coll Cardiol 23:11–18
Hsia J, Hamilton WP, Kleiman N, Roberts R, Chaitman BR, Ross AM (1990) A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin–Aspirin Reperfusion Trial (HART) Investigators. N Engl J Med 323:1433–1437
Chesebro JH, Knatterud G, Roberts R et al (1987) Thrombolysis in Myocardial Infarction (TIMI) Trial phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 76:142–154
Neuhaus KL, Tebbe U, Gottwik M et al (1988) Intravenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarction: results of the German Activator Urokinase Study (GAUS). J Am Coll Cardiol 12:581–587
Califf RM, Topol EJ, Stack RS, et al. (1991) Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of thrombolysis and angioplasty in myocardial infarction – phase 5 randomized trial. TAMI Study Group. Circulation 83:1543–1556
Neuhaus KL, von Essen R, Tebbe U et al (1992) Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS). J Am Coll Cardiol 19:885–891
In-hospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. The International Study Group (1990) Lancet 336:71–75
Granger CB, Hirsch J, Califf RM et al (1996) Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial. Circulation 93:870–878
Antman EM, Hand M, Armstrong PW et al (2008) 2007 Focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 51:210–247
Weitz JI (1997) Low-molecular-weight heparins. N Engl J Med 337:688–698
Kontny F, Dale J, Abildgaard U, Pedersen TR (1997) Randomized trial of low molecular weight heparin (dalteparin) in prevention of left ventricular thrombus formation and arterial embolism after acute anterior myocardial infarction: the Fragmin in Acute Myocardial Infarction (FRAMI) Study. J Am Coll Cardiol 30:962–969
Frostfeldt G, Ahlberg G, Gustafsson G et al (1999) Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction–a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II). J Am Coll Cardiol 33:627–633
Simoons M, Krzeminska-Pakula M, Alonso A et al (2002) Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI-SK study. Eur Heart J 23:1282–1290
Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction (2001) Lancet 358:605–613
Ross AM, Molhoek P, Lundergan C et al (2001) Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II). Circulation 104:648–652
Baird SH, Menown IB, McBride SJ, Trouton TG, Wilson C (2002) Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. Eur Heart J 23:627–632
Antman EM, Louwerenburg HW, Baars HF et al (2002) Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 trial. Circulation 105:1642–1649
Wallentin L, Bergstrand L, Dellborg M et al (2003) Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction – the ASSENT Plus study. Eur Heart J 24:897–908
Wallentin L, Goldstein P, Armstrong PW et al (2003) Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation 108:135–142
Antman EM, Morrow DA, McCabe CH et al (2006) Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med 354:1477–1488
Cohen M, Gensini GF, Maritz F et al (2003) The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial. J Am Coll Cardiol 42:1348–1356
Eikelboom JW, Quinlan DJ, Mehta SR, Turpie AG, Menown IB, Yusuf S (2005) Unfractionated and low-molecular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with st-elevation acute myocardial infarction. Circulation 112:3855–3867
Coussement PK, Bassand JP, Convens C et al (2001) A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study. Eur Heart J 22:1716–1724
Yusuf S, Mehta SR, Chrolavicius S et al (2006) Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 295:1519–1530
Kaminski M, McDonagh J (1987) Inhibited thrombins. Interactions with fibrinogen and fibrin. Biochem J 242: 881–887
Hogg PJ, Jackson CM (1989) Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. Proc Natl Acad Sci USA 86:3619–3623
Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J (1990) Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 86:385–391
Antman EM (1994) Hirudin in acute myocardial infarction. Safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A Trial. Circulation 90:1624–1630
Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIa Investigators (1994) Circulation 90:1631–1637
Antman EM (1996) Hirudin in acute myocardial infarction. Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial. Circulation 94:911–921
Metz BK, White HD, Granger CB, et al. (1998) Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators. J Am Coll Cardiol 31:1493–1498
Neuhaus KL, von Essen R, Tebbe U, et al. (1994) Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte (ALKK). Circulation 90:1638–1642
Neuhaus KL, Molhoek GP, Zeymer U et al (1999) 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 34:966–973
Cannon CP, McCabe CH, Henry TD et al (1994) A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 5 trial. J Am Coll Cardiol 23:993–1003
Lidon RM, Theroux P, Lesperance J et al (1994) A pilot, early angiographic patency study using a direct thrombin inhibitor as adjunctive therapy to streptokinase in acute myocardial infarction. Circulation 89:1567–1572
Theroux P, Perez-Villa F, Waters D, Lesperance J, Shabani F, Bonan R (1995) Randomized double-blind comparison of two doses of Hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction. Circulation 91:2132–2139
White HD, Aylward PE, Frey MJ et al. (1997) Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators. Circulation 96:2155–2161
Direct thrombin inhibitors in acute coronary syndromes: principal results of a meta-analysis based on individual patients’ data (2002) Lancet 359:294–302
Stone GW, Ware JH, Bertrand ME et al (2007) Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management: one-year results from the ACUITY trial. JAMA 298:2497–2506
Lincoff AM, Kleiman NS, Kereiakes DJ et al (2004) Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA 292:696–703
Stone GW, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartman F, Gersh BJ, Pocock SJ, Dangas G, Wong SC, Kirtane AJ, Parise J, Mehran R for the HORIZONS-Trial Investigators (2008) Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 358:2218–2230
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Humana Press, a part of Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Galla, J.M., Askari, A.T. (2010). Antithrombin Therapy for Acute ST-Segment Elevation Myocardial Infarction. In: Askari, A., Lincoff, A. (eds) Antithrombotic Drug Therapy in Cardiovascular Disease. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-235-3_12
Download citation
DOI: https://doi.org/10.1007/978-1-60327-235-3_12
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60327-234-6
Online ISBN: 978-1-60327-235-3
eBook Packages: MedicineMedicine (R0)