American Heart Journal
Volume 143, Issue 2 , Pages 205-216 , February 2002

Persistence of the prothrombotic state after acute coronary syndromes: Implications for treatment

Received 6 March 2001 ,Accepted 2 October 2001.

References 

  1. Fuster V, Fayad Z, Badimon J. Acute coronary syndromes: biology. Lancet. 1999;353(II Suppl):5–9
  2. Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q wave myocardial infarction. Circulation. 1998;97:1195–1206
  3. Davies M. Stability and instability: two faces of coronary atherosclerosis: the Paul Dudley White Lecture 1995. Circulation. 1996;94:2013–2020
  4. Braunwald E, Antman EM, Beasly JW, et al.  ACC/AHA guidelines for the management of patients with unstable angina and non-ST elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with unstable angina). J Am Coll Cardiol. 2000;36:970–1062
  5. Van Belle E, Lablanche JM, Bauters C, et al.  Coronary angioscopic findings in the infarct-related vessel within 1 month of acute myocardial infarction: natural history and the effect of thrombolysis. Circulation. 1998;97:26–33
  6. Merlini PA, Bauer KA, Oltrona L, et al.  Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation. 1994;90:61–68
  7. Merlini PA, Ardissino D, Rosenberg RD, et al.  In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris. Arterioscler Thromb Vasc Biol. 2000;20:2162–2166
  8. Ault KA, Cannon CP, Mithchell J, et al.  Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial. J Am Coll Cardiol. 1999;33:634–639
  9. Topol EJ, Yaday J. Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation. 2000;101:570–580
  10. Ohman EM, Armstrong PW, Christenson R, et al.  Cardiac troponin levels for risk stratification in acute myocardial ischemia. N Engl J Med. 1996;335:1333–1341
  11. Heeschen C, Hamm C, Goldman B, et al.  Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. Lancet. 1999;354:1757–1762
  12. Hamm C, Heeschen C, Goldman B, et al.  Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin levels. N Engl J Med. 1999;340:1623–1629
  13. FRISC Investigators . Long-term molecular mass heparin in unstable coronary artery disease: FRISC II prospective randomized multicentre study. Lancet. 1999;354:701–707
  14. Oler A, Whooley MA, Oler J, et al.  Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: a meta analysis. JAMA. 1996;276:811–815
  15. Theroux P, Waters D, Lam J, et al.  Reactivation of unstable angina after discontinuation of heparin. N Engl J Med. 1992;327:141–145
  16. Granger CB, Hirsh J, Califf RM, et al.  Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial. Circulation. 1996;93:870–878
  17. Granger CB, Becker R, Tracy R, et al.  Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I trial. J Am Coll Cardiol. 1998;31:497–505
  18. Bahit MC, Topol EJ, Califf RM, et al.  Reactivation of ischemic events in acute coronary syndromes: results from GUSTO-IIb. J Am Coll Cardiol. 2001;37:1001–1007
  19. TRIM Study Group . A low molecular weight, selective thrombin inhibitor, inogatran, vs heparin, in unstable coronary artery disease in 1209 patients: a double-blind, randomised, dose-finding study. Eur Heart J. 1997;18:1416–1425
  20. Linder R, Olgren J, Egberg N, et al.  The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease. Eur Heart J. 1999;20:506–518
  21. Mombelli G, Marchetti O, Haeberli A, et al.  Effect of intravenous heparin infusion on thrombin-antithrombin complex and fibrinopeptide A in unstable angina. Am Heart J. 1998;136:1106–1113
  22. Merlini P, Ardissino D, Bauer KA, et al.  Persistent thrombin generation during heparin therapy in patients with acute coronary syndromes. Arterioscler Thromb Vasc Biol. 1997;17:1325–1330
  23. Becker RC, Spencer FA, Li Y, et al.  Thrombin generation after abrupt cessation of intervenous unfractionated heparin among patients with acute coronary syndromes: potential mechanisms for heightened prothrombic potential. J Am Coll Cardiol. 1999;34:1020–1027
  24. Granger CB, Miller JM, Bovill EG, et al.  Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation. 1995;91:1929–1935
  25. Ernofsson M, Strekerud F, Toss H, et al.  Low-molecular weight heparin reduces the generation and activity of thrombin in unstable coronary artery disease. Thromb Hemost. 1998;79:491–494
  26. Greenbaum AB, Harrington RA, Hudson MP, et al.  Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes: PURSUIT Investigators. J Am Coll Cardiol. 2001;37:492–498
  27. ISIS-2 Second International Study of Infarct Survival Collaborative Group . Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;2:349–360
  28. Theroux P, Ouimet H, McCans J, et al.  Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105–1111
  29. Lewis HD, Davis JW, Archibald DG, et al.  Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina: results of a Veterans Administration cooperative study. N Engl J Med. 1983;309:396–403
  30. Cairns JA, Gent M, Singer J, et al.  Aspirin, sulfinpyrazone, or both in unstable angina: results of a Canadian multicenter trial. N Engl J Med. 1985;313:1369–1375
  31. RISC Group . Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet. 1990;336:827–830
  32. Antiplatelet Trialists' Collaboration . Collaborative overview of randomized trials of antiplatelet therapy: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ. 1994;308:81–106
  33. Lindahl B, Toss H, Siegbahm A, et al.  Markers of myocardial damage and inflammation in relation to long term mortality in unstable coronary artery disease: FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl J Med. 2000;343:1139–1147
  34. Gurfinkel E. Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. J Am Coll Cardiol. 1995;26:313–318
  35. Cohen M, Demers C, Gurfinkel E, et al.  A comparison of low molecular heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997;337:447–452
  36. Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAXIS (Fraxiparine in Ischaemic Syndrome). Eur Heart J. 1999;20:1553–1562
  37. Klein W, Buchwald A, Hillis S, et al.  Comparison of low molecular weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Circulation. 1997;96:61–68
  38. Fragmin during Instability in Coronary Artery Disease FRISC Study Group . Low-molecular-weight heparin during instability in coronary artery disease. Lancet. 1996;347:561–568
  39. Antman E, McCabe C, Gurfinkel E, 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. 1999;100:1593–1601
  40. Antman E, Cohen M, Radley D, et al.  Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction: TIMI 11B-ESSENCE meta-analysis. Circulation. 1999;100:1602–1608
  41. Invasive compared with non-invasive treatment in unstable coronary artery disease: FRISC II prospective randomized multicenter study: Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease Investigators. Lancet. 1999;354:708–715
  42. Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis ASPECT Research Group . Effect of long term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet. 1994;343:499–503
  43. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med. 1990;323:147–152
  44. Anand S, Yusuf S, Pogue J, et al.  Long term oral anticoagulant therapy in patients with unstable angina or suspected non Q wave myocardial Infarction: OASIS pilot study results. Circulation. 1998;98:1064–1070
  45. Anand S, Yusuf S. The OASIS investigators: randomised trial of oral anticoagulant therapy in patients with acute ischemic syndromes without ST elevation: importance of good compliance. J Am Coll Cardiol. 1999;33:396A
  46. Coumadin Aspirin Reinfarction Study CARS Investigators . Randomized double-blind trial of fixed low dose warfarin with aspirin after myocardial infarction. Lancet. 1997;350:389–396
  47. Fiore L, Combination Hemotherapy and Mortality Prevention CHAMP study . Plenary Session XII: Late Breaking Clinical Trials. Proceedings of the 72nd Scientific Sessions of the American Heart Association; 1999 Nov 7-10; Atlanta, Ga. Atlanta: The Association; 1999;
  48. Van Es RF. The Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis-2 (ASPECT-2). In: Proceedings of the 22nd Congress of the European Society of Cardiology; 2000 Aug 26-30; Amsterdam, The Netherlands. Amsterdam: The Society; 2000;
  49. Brower MA. The Antithrombotics in the Prevention of Reocclusion in Coronary Thrombosis-2 (APRICOT-2). In: Proceedings of the 22nd Congress of the European Society of Cardiology; 2000 Aug 26-30; Amsterdam, The Netherlands. Amsterdam: The Society; 2000;
  50. Arnesen H, Warfarin-Asprin Re-Infarction Study WARIS II. Plenary Session: Hotline . Proceedings of the 23rd Congress of the European Society of Cardiology; 2001 Sept 2-5; Stockholm, Sweden. Stockholm: The Society; 2001;
  51. CAPRIE Investigators . A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329–1339
  52. CURE Investigators . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502
  53. Mehta SR, Yusuf S, Peters RJG, et al.  Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358:527–533
  54. Chew DP, Bhatt DL, Sapp S, et al.  Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials. Circulation. 2001;103:201–206
  55. O'Neill WW, Serruys P, Knudtson M, et al.  Long-term treatment with a platelet glycoprotein receptor antagonist after percutaneous coronary revascularization. N Engl J Med. 2000;342:1316–1324
  56. Cannon CP, McCabe CH, Wilcox RG, et al.  Oral glycoprotein IIb/IIIa inhibition with orbofiban with unstable coronary syndromes (OPUS TIMI 16) trial. Circulation. 2000;102:149–156
  57. SYMPHONY Investigators . Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial. Lancet. 2000;355:337–345
  58. Second SYMPHONY Investigators . Randomized trial of aspirin, sibrafiban or both for secondary prevention after acute coronary syndromes. Circulation. 2001;103:1727–1733
  59. Topol EJ, Easton D, Amarenco P, et al.  Design of the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial. Am Heart J. 2000;139:927–933
  60. Casey M, Fornari C, Bozovich G, et al.  Increased expression of platelet P-selectin in patients treated with oral orbofiban in the OPUS TIMI 16 trial. [abstract] In: Proceedings of the 72nd Scientific Sessions of the American Heart Association; 1999 Nov 7-10; Atlanta, Ga. Atlanta: The Association; 1999;
  61. Adderley SR, Fitzgerald DJ. Glycoprotein IIb/IIIa antagonist induce apoptosis in rat cardiomyocytes by Caspase-3 activation. J Biol Chem. 2000;275:5760–5766
  62. Califf RM, Woodlief LH, Harrell FE, et al.  Selection of thrombolytic therapy for individual patients: development of a clinical model. GUSTO-I Investigators. Am Heart J. 1997;133:630–639
  63. Lindahl B, Venge P, Wallentin L, et al.  Troponin T identifies patients with unstable coronary artery disease who benefit from long term antithrombotic protection. J Am Coll Cardiol. 1997;29:43–48
  64. Newby LK, Ohman EM, Christenson RH, et al.  Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin T-positive status: the PARAGON-B troponin T substudy. Circulation. 2001;103:2891–2896
  65. Simoons ML, for the GUSTO IV investigators . Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet. 2001;357:1915–1924

☆ Supported by an unrestricted educational grant from Pharmacia & Upjohn, Peapack, NJ.

☆☆ Guest Editor for this manuscript was Richard C. Becker, MD, University of Massachusetts Medical Center, Worcester, Mass.

★ Reprint requests: Maria Cecilia Bahit, MD, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715. E-mail: bahit001@mc.duke.edu

PII: S0002-8703(02)65464-X

doi: 10.1067/mhj.2002.120767

American Heart Journal
Volume 143, Issue 2 , Pages 205-216 , February 2002

Article Tools

* Image Usage & Resolution