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Randomized Trials of Antiplatelet Therapy

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Handbook of Platelet Physiology and Pharmacology

Abstract

Vascular disease is of major importance worldwide as a cause both of death and disability, mainly in middle-aged and elderly individuals. Ischemic heart disease and stroke are the two leading causes of death in the developing world, as well as in the developed world, and accounted for around one fifth of the 50 million deaths worldwide in 1990 (1). Cardiovascular disorders caused almost 10% of all disability worldwide in 1990 (2), and projections suggest that by the year 2020 this will have risen to 15%, with almost all of the increase occurring in developing countries (3).

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References

  1. Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997; 349: 1269–1276.

    Article  CAS  Google Scholar 

  2. Murray CJL, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349:1436–1442.

    Article  CAS  Google Scholar 

  3. Murray CJL, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 1997; 349:1498–1504.

    Article  CAS  Google Scholar 

  4. Peto R, Lopez AD, Boreham J, Thun M, Heath C Jr. Mortality from smoking in developed countries 1950–2000. Indirect estimates from National Vital Statistics. Oxford: Oxford University Press, 1994.

    Google Scholar 

  5. Collins R, Peto R. Antihypertensive Drug Therapy: Effects on Stroke and Coronary Heart Disease. In: Swales JD, ed. Textbook of Hypertension. Oxford: Blackwell Scientific Publications, 1994: 1156–1164.

    Google Scholar 

  6. Collins R, Peto R, Gray R, Parish S. Large-scale randomized evidence: trials and overviews. In: Weatherall DJ, Ledingham JGG, Warrell DA, eds. Oxford Textbook of Medicine Oxford: Oxford University Press, 1996: 21–32.

    Google Scholar 

  7. Early Breast Cancer Trialists’ Collaborative Group. Treatment of early breast cancer. Vol 1. Worldwide evidence 1985–1990. Oxford: Oxford University Press, 1990: 12–18.

    Google Scholar 

  8. Antiplatelet Trialists“ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy — I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994; 308: 81–106.

    Article  Google Scholar 

  9. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy — II: Maintenance of vascular graft or arterial patency by antiplatelet therapy. BMJ 1994; 308: 159–168.

    Article  Google Scholar 

  10. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy — III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. BMJ 1994; 308: 235–246.

    Article  Google Scholar 

  11. Patrono C. Aspirin as an antiplatelet drug. N Engl J Med 1994; 330: 1287–1294.

    Article  CAS  Google Scholar 

  12. Fitzgerald GA. Dipyridamole. N Engl J Med 1987; 316: 1247–1257.

    Article  CAS  Google Scholar 

  13. Diener HC, Cunha L, Forbes C, Sivenius J, Smuts P, Lowenthal A. European Secondary Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143: 1–13.

    Article  CAS  Google Scholar 

  14. Sudlow C, Baigent C, on behalf of the Antithrombotic Trialists’ Collaboration. Different antiplatelet regimens in the prevention of vascular events among patients at high risk of stroke: new evidence from the Antithrombotic Trialists’ Collaboration. (Seventh European Stroke Conference, Edinburgh, May, 1998). Cerebrovascular Diseases 1998; 8(suppl 4): 68.

    Google Scholar 

  15. Savi P, Heilmann E, Nurden P, et al. Clopidogrel: an antithrombotic drug acting on the ADP-dependent activation pathway of human platelets. Clin Appl Thromb Hemost 1996; 2: 35–42.

    Article  Google Scholar 

  16. CAPRIE Steering Committee. A randomised, blinded, trial of Clopidogrel versus aspirin in patients at risk of ischemic events. Lancet 1996; 348: 1329–1339.

    Article  Google Scholar 

  17. Ferguson JJ, Waly HM, Wilson JM. Fundamentals of coagulation and glycoprotein IIb/IIIa receptor inhibition. Eur Heart J 1998; 19(Suppl D): D3–D9.

    CAS  Google Scholar 

  18. Braunwald E, Maseri A, Armstrong PW, et al. Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes. Eur Heart J 1998; 19(Suppl D): D22–D30.

    CAS  Google Scholar 

  19. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high risk coronary angioplasty. N Engl J Med 1994; 330:956–961.

    Article  Google Scholar 

  20. Lincoff AM, Califf RM, Anderson K, et al. Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIb/IIIa receptor blockade by abciximab (c7E3 Fab) among patients with unstable angina undergoing percutaneous coronary revascularization. J Am Coll Cardiol 1997; 30:149–156.

    Article  CAS  Google Scholar 

  21. Topol EJ, Ferguson JJ, Weisman HF, et al. Long-term protection from myocardial ischemic events in a randomized trial of integrin ß3 blockade with percutaneous coronary intervention. JAMA 1997; 278: 479–484.

    Article  CAS  Google Scholar 

  22. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689–1696.

    Article  Google Scholar 

  23. The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997; 349: 1429–1435.

    Article  Google Scholar 

  24. The IMPACT-II Investigators. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Lancet 1997; 349:1422–1428.

    Article  Google Scholar 

  25. The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation 1997; 96: 1445–1453.

    Article  Google Scholar 

  26. Califf RM. PURSUIT. Presented at the 70th Scientific Sessions of the American Heart Association; November, 1997, Orlando, Florida, USA.

    Google Scholar 

  27. Theroux P, Kouz S, Roy L, et al. Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina: the Canadian Lamifiban Study. Circulation 1996; 94: 899–905.

    Article  CAS  Google Scholar 

  28. Alexander JH, Newby LK, Moliterno DJ, et al. Relationship of outcomes to treatment with lamifiban in patients undergoing PTCA: analysis of PARAGON A (abstract). J Am Coll Cardiol 1997; 29:409A.

    Google Scholar 

  29. Van de Werf F. PARAGON. Presented at the 19th Congress of the European Society of Cardiology; August, 1997, Stockholm, Sweden.

    Google Scholar 

  30. The PRISM-PLUS Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. New Engl J Med 1998; 338: 1488–1497.

    Article  Google Scholar 

  31. Kleiman NS, Ohman EM, Califf RM, et al. Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy: results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 pilot study. J Am Coll Cardiol 1993; 22: 381–389.

    Article  CAS  Google Scholar 

  32. Ohman EM, Kleiman NS, Gacioch G, et al. Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with integrilin in acute myocardial infarction: results of a randomized, placebo-controlled, dose-ranging trial. Circulation 1997; 95: 846–854.

    Article  CAS  Google Scholar 

  33. Brener SJ, Barr LA, Burchenal J, et al. A randomized, placebo-controlled trial of abciximab with primary angioplasty for acute MI: the RAPPORT trial (abstract). Circulation 1997; 96(suppl I):I–473.

    Google Scholar 

  34. Harrington RA PARADIGM Presented at the 69th Scientific Sessions of the American Heart Association; November 1996, New Orleans, La, USA.

    Google Scholar 

  35. Molitorio DJ, Topol EJ. Meta-analysis of platelet GP IIb/IIIa antagonist randomized clinical trials in ischemic heart disease: consistent, durable, salutary effects. Circulation 1997; 96(suppl I): I–475.

    Google Scholar 

  36. Narins CR, Topol EJ. Attention shifts to the white clot Lancet 1997; 350(suppl III): 2.

    Google Scholar 

  37. Ferguson JJ, Kereiakes DJ, Adgey AAJ, et al. Safe use of GP IIb/IIIa inhibitors. Eur Heart J 1998; 19(Suppl D): D40–D51.

    CAS  Google Scholar 

  38. Cannon CP, McCabe CH, Borzak S, et al. Randomized trial of an oral platelet glycoprotein IIb/IIIa antagonist, sibrofiban, in patients after an acute coronary syndrome: results of the TIMI 12 Trial. Circulation 1998; 97: 340–349.

    Article  CAS  Google Scholar 

  39. Dyken ML, Barnett HJM, Easton JD, Fields WS, Fuster V, Hachinski V et al. Low-dose aspirin and stroke. “It ain’t necessarily so”. Stroke 1992; 23: 1395–1399.

    Article  CAS  Google Scholar 

  40. Barnett HJM, Kaste M, Meldrum H, Eliasziw M. Aspirin dose in stroke prevention. Beautiful hypotheses slain by ugly facts. Stroke 1996; 27: 588–592.

    Article  CAS  Google Scholar 

  41. UK-TIA Study Group. The United Kingdom transient ischemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991; 54:1044–1054.

    Article  Google Scholar 

  42. The Dutch TIA Study Group. A comparison of two doses of aspirin (30mg vs 283mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 1991; 325: 1261–1266.

    Article  Google Scholar 

  43. SALT Collaborative Group. Swedish aspirin low-dose trial (SALT) of 75mg aspirin as secondary prophylaxis after cerebrovascular ischemic events. Lancet 1991; 338: 1345–1349.

    Article  Google Scholar 

  44. Juul-Moller S, Edvardsson N, Jahnmatz B, Rosen A, Soreneson S, Omblus R, for the Swedish Angina Pectoris Aspirin Trial (SAPAT) Group. Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. Lancet 1992; 340:1421–1425.

    Article  CAS  Google Scholar 

  45. Patrono C, Ciabattoni G, Patrigiani P, et al. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation 1985; 72: 1177–1184.

    Article  CAS  Google Scholar 

  46. Sandercock PAG, van den Belt AGM, Lindley RI, Slattery J. Antithrombotic therapy in acute ischemic stroke: an overview of the completed randomised trials. J Neurol Neurosurg Psychiatry 1993; 56: 17–25.

    Article  CAS  Google Scholar 

  47. International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both or neither among 19,435 patients with acute ischemic stroke. Lancet 1997; 349: 1569–1581.

    Article  Google Scholar 

  48. CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischemic stroke. Lancet 1997; 349: 1641–1649.

    Article  Google Scholar 

  49. Multicentre Acute Stroke Trial — Italy (MAST-I) Group. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischemic stroke. Lancet 1995; 346:1509–1514.

    Google Scholar 

  50. Peto R, Gray R, Collins R, et al. Randomized trial of prophylactic daily aspirin in British male doctors. BMJ 1988; 296: 313–316.

    Article  CAS  Google Scholar 

  51. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing physicians’ health study. N Engl J Med 1989; 321:129–135.

    Article  Google Scholar 

  52. The Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischemic heart disease in men at increased risk. Lancet 1998; 351: 233–241.

    Article  Google Scholar 

  53. Hanssem L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: 1755–1762.

    Article  Google Scholar 

  54. Gillum RF. Coronary artery bypass surgery and coronary angiography in the United States, 1979–1985. Am Heart J 1987; 113: 1255–1260.

    Article  CAS  Google Scholar 

  55. Fuster V, Chesebro JH. Role of platelets and platelet inhibitors in aorto-coronary vein graft disease. Circulation 1986; 73: 227–232.

    Article  CAS  Google Scholar 

  56. Cainpean L, Enjalbert M, Leoperance J. The relation of risk factors to the development of atherosclerosis in saphenous vein bypass grafts. N Engl J Med 1984; 311: 1329–1332.

    Article  Google Scholar 

  57. Detre KM, Holubkov R, Kelsey SF, Cowley M, Kent KM, Williams DK, et al. Percutaneous transluminal coronary angioplasty in 1985–1986 and 1977–1981. N Engl J Med 1988; 318: 265–270.

    Article  CAS  Google Scholar 

  58. MacMahon S, Raine A. Mortality from myocardial infarction among dialysis and renal transplant patients in Britain. Circulation 1990; 82(Suppl 3): 615.

    Google Scholar 

  59. Pirk J, Ruzbarsky V, Kunig J. The effect of antiaggregating drugs on the patency of grafts in the arterial system. World J Surg 1980; 4: 615–620.

    Article  CAS  Google Scholar 

  60. Bonchek LI, Boerboom LE, Olinger GN. Prevention of lipid accumulation in experimental vein bypass by antiplatelet therapy. Circulation 1982; 66: 338–341.

    Article  CAS  Google Scholar 

  61. Antiplatelet Trialists’ Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet treatment. BMJ 1988; 296: 320–331.

    Article  Google Scholar 

  62. Israel DH, Adams PC, Stein B, Chesebro JH, Fuster V. Antithrombotic therapy in the coronary vein graft patient. Clin Cardiol 1991; 14: 283–295.

    Article  CAS  Google Scholar 

  63. Thromboembolic Risk Factors (THRIFT) Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. BMJ 1992; 305: 567–574.

    Article  Google Scholar 

  64. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. N Engl J Med 1988; 318: 1162–1173.

    Article  CAS  Google Scholar 

  65. Leizorovicz A, Haugh MC, Chapuis F-R, Boissel J-P. Low molecular weight heparin in the prevention of perioperative thrombosis. BMJ 1992; 305: 567–574.

    Article  Google Scholar 

  66. Consensus Development Conference Report. Prevention of venous thrombosis and pulmonary embolism. JAMA 1986; 256: 744–749.

    Article  Google Scholar 

  67. Collins R, Baigent C, Sandercock P, Peto R, for the Antiplatelet Trialists’ Collaboration. Antiplatelet therapy for thromboprophylaxis: the need for careful consideration of the evidence from randomised trials. BMJ 1994; 309:1215–1217.

    Article  CAS  Google Scholar 

  68. Huber O, Bounameaux H, Borst F, Rohner A. Postoperative pulmonary embolism after hospital discharge. An underestimated risk. Arch Surg 1992; 127: 310–313.

    Article  CAS  Google Scholar 

  69. Roderick PJ, Wilkes HC, Meade TW. The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials. Br J Clin Pharmacol 1993; 35: 219–226.

    Article  CAS  Google Scholar 

  70. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project 1981–1986. 2. Incidence, case fatality and overall outcome at one year of cerebral infarction, primary intracerebral hemorrhage and subarachnoid hemorrhage. J Neurol Neurosurg Psychiatry 1990; 53: 16–22.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford Radcliffe Infirmary, Oxford, OX2 6HE, UK

    Cathie L. M. Sudlow & Colin N. Baigent

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  1. Cathie L. M. Sudlow
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  2. Colin N. Baigent
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Editors and Affiliations

  1. Departments of Lab. Med. & Pathol. and Biomed. Engineering, UMHC, P. B. 609, USA

    Gundu H. R. Rao Ph. D.

  2. Academic Health Center, University of Minnesota, Minneapolis, MN, 55455, USA

    Gundu H. R. Rao Ph. D.

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Sudlow, C.L.M., Baigent, C.N. (1999). Randomized Trials of Antiplatelet Therapy. In: Rao, G.H.R. (eds) Handbook of Platelet Physiology and Pharmacology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5049-5_24

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  • DOI: https://doi.org/10.1007/978-1-4615-5049-5_24

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7295-0

  • Online ISBN: 978-1-4615-5049-5

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