Advertisement

Antithrombotic Therapy in Unstable Angina and Non-Q-Wave Myocardial Infarction

  • Marc Cohen
  • Reginald Blaber
Part of the Contemporary Cardiology book series (CONCARD)

Abstract

Unstable angina is a broad term representing a wide spectrum of ischemic coronary syndromes, ranging from progressive or accelerating angina to the high-risk subset of patients with rest angina and reversible electrocardiographic (ECG) changes. The underlying precipitant is the ruptured or fissured coronary plaque, which elicits a complex interaction between the coagulation cascade and platelets to form a thrombus. The majority of these disruptions and resulting thrombi cause only insignificant obstruction to coronary blood flow. However, a large thrombus can cause a significant impediment to coronary flow, resulting in ischemia. This thrombus may resolve spontaneously, with restoration of blood flow, or may propagate to cause further ischemia. Often this process can lead to complete occlusion of the vessel, precipitating a myocardial infarction (MI) (1–10). Unstable angina and non-Q-wave myocardial infarction (NQMI) represent two different points within the continuum of coronary thrombosis.

Keywords

Unstable Angina Deep Venous Thrombosis Unfractionated Heparin Antithrombotic Therapy Direct Thrombin Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fuster, V. Elucidation of the role of plaque instability and rupture in acute coronary events. Am J Cardiol 1995; 76: 24C - 33C.PubMedCrossRefGoogle Scholar
  2. 2.
    Falk E, Shah P, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657–670.PubMedCrossRefGoogle Scholar
  3. 3.
    Stein B, Fuster V, Halperin J, Chesebro J. Antithrombotic therapy in cardiac disease: an emerging approach based on pathogenesis and risk. Circulation 1989; 80: 1502–1513.CrossRefGoogle Scholar
  4. 4.
    Fuster V, Badimon L, Cohen M, Ambrose J, Badimon J, Chesebro J. Insights into the pathogenesis of acute ischemic syndromes. Circulation 1988; 77: 1213–1220.PubMedCrossRefGoogle Scholar
  5. 5.
    Fuster V, Stein B, Ambrose J, Badimon L, Badimon J, Chesebro J. Atherosclerotic plaque rupture and thrombosis: evolving concepts. Circulation 1990; 82 (Suppl II): 47–59.Google Scholar
  6. 6.
    Fuster V. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 1994; 90: 2126–2146.PubMedCrossRefGoogle Scholar
  7. 7.
    Theroux P, Lidon R. Unstable angina: pathogenesis, diagnosis, and treatment. Cliff Probl Cardiol 1993; 18: 157–231.Google Scholar
  8. 8.
    Cairns J, Lewis D, Jr, Meade T, Sutton G, Theroux P. Antithrombotic agents In coronary artery disease. Chest 1995; 108 (Suppl): 380S - 400S.PubMedCrossRefGoogle Scholar
  9. 9.
    Grambow D, Topol E. Effect of maximal medical therapy on refractoriness of unstable angina pectoris. Am J Cardiol 1992; 70: 577–581.PubMedCrossRefGoogle Scholar
  10. 10.
    Jaffrani N, Ehrenpreis S, Laddu A, Somberg J. Theapeutic approach to unstable angina: nitroglycerin, heparin, and combined therapy. Am Heart J 1993; 126: 1239–1242.PubMedCrossRefGoogle Scholar
  11. 11.
    DeWood M, Spores J, Notske R, Mouser L, Burroughs R, Golden M et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980; 303: 897–902.PubMedCrossRefGoogle Scholar
  12. 12.
    Lewis H, Davis J, Archibald D, Steinke W, Steinke W, Smitherman T, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med 1983; 309: 396–403.PubMedCrossRefGoogle Scholar
  13. 13.
    Cairns J, Gent M, Singer J, Finnie K, Froggartt G, Holder D, et al. Aspirin, sulfinpyrazone or both in unstable angina: results of a Canadian Multicenter Trial. N Engl J Med 1985; 313: 1369–1375.PubMedCrossRefGoogle Scholar
  14. 14.
    The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable angina. Lancet 1990; 336: 827–830.CrossRefGoogle Scholar
  15. 15.
    Balsano F, Rizzon P, Violi F, Scrutino D, Cimminiello C, Aguglia F, et al., STAI Group. Antiplatelet treatment with ticlopidine in unstable angina: a controlled multicenter clinical trial. Circulation 1990; 82: 17–26.PubMedCrossRefGoogle Scholar
  16. 16.
    Oler A, Whooley M, Oler J, Grady D. 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Willard J, Lange R, Hillis L. The use of aspirin in ischemic heart disease. N Engl J Med 1992; 327: 175–181.PubMedCrossRefGoogle Scholar
  18. 18.
    Patrono C. Aspirin as an Antiplatelet Drug. N Engl J Med 1994; 330: 1287–1294.PubMedCrossRefGoogle Scholar
  19. 19.
  20. 20.
    Theroux P, Ouimet H, McCans J, Latour J, Joly P, Levy G, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988; 319: 1105–1111.PubMedCrossRefGoogle Scholar
  21. 21.
    Cohen M, Parry G, Adams P, Xiong J, Chamberlain D, Wieczorek I, et al, and the ATAC Research Group. Prospective evaluation of a prostacyclin-sparing aspirin formulation and heparin/warfarin in aspirin users with unstable angina or non-Q-wave myocardial infarction at rest. Eur Heart J 1994; 15: 1196–1203.PubMedGoogle Scholar
  22. 22.
    Montgomery H, Chester M. Heparin in unstable angina. Lancet 1995; 346: 245.CrossRefGoogle Scholar
  23. 23.
    Hirsh, J. Heparin. N Engl J Med 1991: 324: 1565–1574.CrossRefGoogle Scholar
  24. 24.
    Yusuf S, Wittes J, Friedman L. Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction. JAMA 1988; 260: 2088–2093.PubMedCrossRefGoogle Scholar
  25. 25.
    Hennekens D, O’Donnell C, Ridker P. Current and future perspectives on antithrombotic therapy of acute myocardial infarction. Eur Heart J 1995; 16 (Suppl D): 2–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Telford A, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome. Lancet 1981; 1: 1225–1228.PubMedCrossRefGoogle Scholar
  27. 27.
    Theroux P, Waters D, Qui S, McCans J, deGuise P, Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993; 88: 2045–2048.PubMedCrossRefGoogle Scholar
  28. 28.
    Neri Serneri G, Gensini G, Poggesi L, Trotta F, Modesti P, Boddi M, et al. Effect of heparin, aspirin, or alteplase in reduction of myocardial ischaemia in refractory unstable angina. Lancet 1990; 335: 615–618.CrossRefGoogle Scholar
  29. 29.
    Neri Serneri G, Modesti P, Gensini G, Branzi A, Melandri G, Poggesi L, et al., for the SESAIR Group. Randomised comparison of subcutaneous heparin, intravenous heparin, and aspirin in unstable angina. Lancet 1995; 345: 1201–1204.CrossRefGoogle Scholar
  30. 30.
    Theroux P, Waters D, Lam J, Juneau M, McCans. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992; 327: 141–145.PubMedCrossRefGoogle Scholar
  31. 31.
    Cohen M, Adams P, Parry G, Xiong J, Chamberlain D, Wieczorek I, et al., and the Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users primary end points analysis from the ATACS Trial. Circulation 1994; 89: 81–88.PubMedCrossRefGoogle Scholar
  32. 32.
    Holdright D, Patel D, Cunningham D, Thomas R, Hubbard W, Hendry G, et al. Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. J Am Coll Cardio11994; 24: 39–45.Google Scholar
  33. 33.
    Lefkovits J, Topol E. Direct thrombin inhibitors in cardiovascular medicine. Circulation 1994; 90: 1522–1536.PubMedCrossRefGoogle Scholar
  34. 34.
    Lidon R, Theroux P, Juneau M, Adelman B, Maraganore J. Initial experience with a direct anti-thrombin, hirulog, in unstable angina. Anticoagulant, antithrombotic, and clinical effects. Circulation 1993; 88: 1495–1501.PubMedCrossRefGoogle Scholar
  35. 35.
    Cannon C, Braunwald E. Hirudin: initial results in acute myocardial infarction, unstable angina and angioplasty. J Am Coll Cardiol 1995; 25 (Suppl): 30S - 37S.PubMedCrossRefGoogle Scholar
  36. 36.
    Heras M, Chesebro J, Webster M, Mruk J, Grill D, Penny W, et al. Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis. Circulation 1990; 82: 1476–1484.PubMedCrossRefGoogle Scholar
  37. 37.
    Sharma G, Lapsley D, Vita J, Sharma S, Coccio E, Adelman B, et al. Safety and efficacy of hirolog in patients with unstable angina. Circulation 1992;(Suppl I):I-386 (abstract).Google Scholar
  38. 38.
    Cannon C, McCabe C, Henry T, et al. A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: results of TIMI 5 Trial. J Am Coll Cardiol 1994; 23: 993–1003.PubMedCrossRefGoogle Scholar
  39. 39.
    Topol E, Fuster V, Harrington R, Califf R, Kleiman N, Kereiakes D, et al. Recombinant hirudin for unstable angina pectoris-a multicenter, randomized angiographic trial. Circulation 1994; 89: 1557–1566.PubMedCrossRefGoogle Scholar
  40. 40.
    Fuchs J, Cannon C, the TIMI 7 Investigators. Hirulog in the treatment of unstable angina. Results of the TIMI 7 Trial. Circulation 1995; 92: 727–733.PubMedCrossRefGoogle Scholar
  41. 41.
    The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb Investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Engl J Med 1996; 335: 775–782.CrossRefGoogle Scholar
  42. 42.
    Antman E, for the TIMI 9B Investigators. Hirudin in acute myocardial infarction: thrombolysis and thrombin inhibition in myocardial infarction (TIMI) 9B TRIAL. Circulation 1996; 94: 911–921.PubMedCrossRefGoogle Scholar
  43. 43.
    Hirsh J, Levine M. Low molecular weight heparin. Blood 1992; 79: 1–17.PubMedGoogle Scholar
  44. 44.
    Cohen M, Blaber R. Potential uses of a new class of low-molecular-weight heparins in cardiovascular indications. Thromb Hemost 1996; 22 (Suppl 2): 25–27.Google Scholar
  45. 45.
    Samama M, Bara L, Gerotziafas G. Mechanisms for the antithrombotic activity in man of low molecular weight heparins. Haemostasis 1994; 24: 105–117.PubMedGoogle Scholar
  46. 46.
    Waters D, Azar R. Low-molecular-weight heparins for unstable angina: a better mousetrap? Circulation 1997; 96: 3–5.PubMedGoogle Scholar
  47. 47.
    Carter C, Kelton J, Hirsh J, Cerkus A, Santos A, Gent M. The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982; 59: 1239–1245.PubMedGoogle Scholar
  48. 48.
    Nurmohamed M, Rosendaal F, Buller H, Dekker E, Hommes D, Vandenbroucke J, et al. Low molecular weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet 1992; 340: 152–156.PubMedCrossRefGoogle Scholar
  49. 49.
    Leclerc J, Geerts W, Desjardins L, Jobin F, Laroche F, Delorme F, et al. Prevention of deep venous thrombosis after major knee surgery-a randomized, double blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost1992; 67: 417–423.Google Scholar
  50. 50.
    Hull R, Raskob G, Pineo G, et al. A comparison of subcutaneous low molecular weight heparin with warfarin sodium for prophylaxis against deep vein thrombosis after hip or knee implantation. N Engl J Med 1993; 329: 1370–1376.PubMedCrossRefGoogle Scholar
  51. 51.
    Spiro T, Johnson G, Christie M, Lyons R, MacFarlane D, Blasier R, et al., for the Enoxparin Clinical Trial Group. Efficacy and safety of enoxaparin to prevent deep venous thrombosis after hip replacement surgery. Ann Intern Med 1994; 121: 81–89.PubMedCrossRefGoogle Scholar
  52. 52.
    Green D, Chen D, Chmiel J, Olsen N, Berkowitz M, Novick A, et al. Prevention of thromboembolism in spinal cord injury: role of low molecular weight heparin. Arch Phys Med Rehabil 1994; 75: 290–292.PubMedCrossRefGoogle Scholar
  53. 53.
    Kakkar V, Cohen A, Edmonson R, Phillips M, Cooper D, Das K, et al. Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. Lancet 1993; 341: 259–265.PubMedCrossRefGoogle Scholar
  54. 54.
    Prandoni P, Lensing A, Buller H, Carta M, Cogo A, Vigo M, et al. Comparison of subcutaneous low molecular weight heparin in proximal deep venous thrombosis. Lancet 1992; 339: 441–445.PubMedCrossRefGoogle Scholar
  55. 55.
    Hull R, Raskob G, Pineo G, Green D, Trowgridge A, et al. Subcutaneous low molecular weight heparin in the treatment of proximal vein thrombosis. N Engl J Med 1992; 326: 975–982.PubMedCrossRefGoogle Scholar
  56. 56.
    Lensing A, Prins M, Davidson B, Hirsh J. Treatment of deep venous thrombosis with low molecular weight heparins: a meta-analysis. Arch Intern Med 1995; 155: 601–607.PubMedCrossRefGoogle Scholar
  57. 57.
    Levine M, Gent M, Hirsh J, Leclerc J, et al. A comparison of low molecular weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep vein thrombosis. N Engl J Med 1996; 334: 677–681.PubMedCrossRefGoogle Scholar
  58. 58.
    Koopman M, Prandoni P, Piovella F, Ockelford P, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low molecular weight heparin administered at home. N Engl J Med 1996; 334: 682–687.PubMedCrossRefGoogle Scholar
  59. 59.
    Leizorovicz A, Simoneau G, Decousus H, Boissel J. Comparison of efficacy and safety of low molecular weight heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ 1994; 309: 299–304.PubMedCrossRefGoogle Scholar
  60. 60.
    Edmondson R, Cohen A, Das S, Wagner M, Kakkar V. Low molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting. Lancet 1994; 344: 914–918.PubMedCrossRefGoogle Scholar
  61. 61.
    Kay R, Wong D, Yu Y, Chan Y, Tsoi T, Ahuj a A, et al. Low molecular weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995; 333: 1588–1593.PubMedCrossRefGoogle Scholar
  62. 62.
    Gurfinkel E, Manos E, Mejail R, Cerda M, Duronto E, Garcia C, et al. 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.PubMedCrossRefGoogle Scholar
  63. 63.
    Wallentin L, for the Fragmin During Instability in Coronary Artery Disease (FRISC) Group. Low molecular weight heparin during instability in coronary artery disease. Lancet 1996; 347: 561–568.Google Scholar
  64. 64.
    Klein, W, Buchwald A, Hillis S, Monrad S, Sanz G, Turpie G, et al., for the FRIC Investigators. Comparison of low molecular weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: Fragmin in Unstable Coronary Artery Disease Study (FRIC). Circulation 1997; 96: 61–68.PubMedCrossRefGoogle Scholar
  65. 65.
    Cohen M et al. Primary end point analysis from the ESSENCE Trial: enoxaparin versus unfractionated heparin in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1997; 337: 447–452.PubMedCrossRefGoogle Scholar
  66. 66.
    Antman E, McCabe, Marble S, Cannon C, Feldman R, Papuchis G, et al. for the TIMI 11A Investigators. Dose ranging trial of enoxaparin for unstable angina: results of TIMI 11A. J Am Coll Cardiol 1997; 29: 1474–1482.CrossRefGoogle Scholar
  67. 67.
    Antman EM. TIMI 11B Trial. Presented at The European Society of Cardiology, Vienna, August 1998.Google Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Marc Cohen
  • Reginald Blaber

There are no affiliations available

Personalised recommendations