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Review1 December 1991

Antithrombotic Therapy in Cerebrovascular Disease

    Author, Article, and Disclosure Information
    https://doi.org/10.7326/0003-4819-115-11-885

    Abstract

    ▪ For more than two decades, anticoagulant and antiplatelet agents have been used routinely to prevent and treat ischemic stroke. Although recent clinical trials have shown that such treatment can be helpful in certain cases, antithrombotic therapy currently remains of unproven benefit in many clinical settings of cerebrovascular disease. Although the absence of data confirming clinical efficacy has generated uncertainty and hesitancy in some clinicians, the lingering conviction that antithrombotic therapy is efficacious has led others to continue a policy of routine and active therapeutic intervention. A critical analysis of the literature on antithrombotic therapy and cerebrovascular disease suggests that many acceptable management options lie between the extremes of therapeutic nihilism and "routine" intervention.

    References

    • 1. Byer J and Easton J. Therapy of ischemic cerebrovascular disease. Ann Intern Med. 1980;93:742-56. LinkGoogle Scholar
    • 2. Brust J. Transient ischemic attacks: natural history and anticoagulation. Neurology. 1977;27:701-7. CrossrefMedlineGoogle Scholar
    • 3. Conneally P, Dyken M, Futty D, Poskanzer D, Calanchini P, and Swanson P. Cooperative study of hospital frequency and character of transient ischemic attacks. VIII. Risk factors. JAMA. 1978;240:742-6. CrossrefMedlineGoogle Scholar
    • 4. Miller V and Hart R. Heparin anticoagulation in acute brain ischemia. Stroke. 1988;19:403-6. CrossrefMedlineGoogle Scholar
    • 5. Phillips S. An alternative view of heparin anticoagulation in acute focal brain ischemia. Stroke. 1989;20:295-8. CrossrefMedlineGoogle Scholar
    • 6. Sage J. The use and overuse of heparin in therapeutic trials. Arch Neurol. 1985;42:315-6. CrossrefMedlineGoogle Scholar
    • 7. Scheinberg P. Controversies in the management of cerebral vascular disease. Neurology. 1988;38:1609-16. CrossrefMedlineGoogle Scholar
    • 8. Scheinberg P. Heparin anticoagulation [Editorial]. Stroke. 1989;20:173-4. CrossrefMedlineGoogle Scholar
    • 9. Sherman D, Dyken M, Fisher M, Harrison M, and Hart R. Cerebral embolism. Chest. 1986;89 (2 Suppl):82S-98S. CrossrefMedlineGoogle Scholar
    • 10. Slivka A and Levy D. Natural history of progressive ischemic stroke in a population treated with heparin. Stroke. 1990:21:1657-62. CrossrefMedlineGoogle Scholar
    • 11. Biller J, Bruno A, Adams H, Godersky J, Loftus C, and Mitchell V. A randomized trial of aspirin or heparin in hospitalized patients with recent transient ischemic attacks. Stroke. 1989;20:441-7. CrossrefMedlineGoogle Scholar
    • 12. Duke R, Bloch R, Turpie A, Trebilcock R, and Bayer N. Intravenous heparin for the prevention of stroke progression in acute partial stable stroke. Ann Intern Med. 1986;105:825-8. LinkGoogle Scholar
    • 13. Levine M and Hirsh J. Hemorrhagic complications of long-term anticoagulant therapy for ischemic cerebral vascular disease. Stroke. 1986;17:111-6. CrossrefMedlineGoogle Scholar
    • 14. Keith D, Phillips S, Whisnant J, Nishimaru K, and O'Fallon W. Heparin therapy for recent transient focal cerebral ischemia. Mayo Clin Proc. 1987;62:1101-6. CrossrefMedlineGoogle Scholar
    • 15. Laureno R, Shields R, and Narayan T. The diagnosis and management of cerebral embolism and hemorrhagic infarction with sequential computerized cranial tomography. Brain. 1987;110:93-105. CrossrefMedlineGoogle Scholar
    • 16. Lodder J, Dennis M, Van Raak L, Jones L, and Warlow C. Cooperative study on the value of long term anticoagulation in patients with stroke and non-rheumatic atrial fibrillation. Br Med J [Clin Res]. 1988;296:1435-8. CrossrefMedlineGoogle Scholar
    • 17. Putnam S and Adams H. Usefulness of heparin in initial management of patients with recent transient ischemic attacks. Arch Neurol. 1985;42:960-2. CrossrefMedlineGoogle Scholar
    • 18. Ramirez-Lassepas M, Quinones M, and Nino H. Treatment of acute ischemic stroke. Open trial with continuous intravenous heparinization. Arch Neurol. 1986;43:386-90. CrossrefMedlineGoogle Scholar
    • 19. Sackett D. Rules of evidence and clinical recommendations on the use of antithrombotic agents. Chest. 1986;89 (2 Suppl):2S-4S. CrossrefMedlineGoogle Scholar
    • 20. Marsh E, Adams H, Biller J, Wasek P, Banwart K, and Mitchell V. Use of antithrombotic drugs in treatment of acute stroke: a survey of neurologists in practice in the United States. Neurology. 1989;39:1631-4. CrossrefMedlineGoogle Scholar
    • 21. Britton M and Roden A. Progression of stroke after arrival at hospital. Stroke. 1985;16:629-33. CrossrefMedlineGoogle Scholar
    • 22. Duke R, Turpie A, Bloch R, and Trebilcock R. Clinical trial of low-dose subcutaneous heparin for the prevention of stroke progression. In: Reivich M, Hurting HI, eds. Cerebrovascular Diseases. New York: Raven Press; 1983:399-405. Google Scholar
    • 23. Jones H, Millikan C, and Sandok B. Temporal profile (clinical course) of acute vertebrobasilar system cerebral infarction. Stroke. 1980;11:173-8. CrossrefMedlineGoogle Scholar
    • 24. Jones H and Millikan C. Temporal profile (clinical course) of acute carotid system cerebral infarction. Stroke. 1976;7:64-71. CrossrefMedlineGoogle Scholar
    • 25. Patrick B, Ramirez-Lassepas M, and Synder B. Temporal profile of vertebrobasilar territory infarction. Prognostic implications. Stroke. 1980;11:643-8. CrossrefMedlineGoogle Scholar
    • 26. Price T. Progressing ischemic stroke. In: Barnett HJ, Mohr JP, Stein BM, Yatsu FM, eds. Stroke: Pathophysiology, Diagnosis, and Management. New York: Churchill Livingstone; 1986:1059-68. Google Scholar
    • 27. Price T, Tuhrim S, Wolf C, Wolf P, Mohr J, and Hier D. Evolving ischemic infarction: The NINCDS Stroke Data Bank (Abstract). Stroke. 1986;17:141. Google Scholar
    • 28. Davalos A, Cendra E, Teruel J, Martinez M, and Genis D. Deteriorating ischemic stroke: risk factors and prognosis. Neurology. 1990;40:1865-9. CrossrefMedlineGoogle Scholar
    • 29. Dobkin B. Heparin for lacunar stroke in progression. Stroke. 1983;14:421-3. CrossrefMedlineGoogle Scholar
    • 30. Lodder J and Gorsselink E. Progressive stroke caused by CT-verified small deep infarcts; relation with the size of the infarct and clinical outcome. Acta Neurol Scand. 1985;71:328-30. CrossrefMedlineGoogle Scholar
    • 31. Mohr J, Caplan L, Melski J, Goldstein R, Duncan G, and Kistler J. The Harvard Cooperative Stroke Registry: a prospective registry. Neurology. 1978;28:754-762. CrossrefMedlineGoogle Scholar
    • 32. Fisher C. The "herald hemiparesis" of basilar artery occlusion. Arch Neurol. 1988;45:1301-3. CrossrefMedlineGoogle Scholar
    • 33. Gautier J. Stroke-in-progression. Stroke. 1985;16:729-33. CrossrefMedlineGoogle Scholar
    • 34. Irino T, Watanabe M, Nishide M, Gotoh M, and Tsuchiya T. Angiographical analysis of acute cerebral infarction followed by "cascades-like deterioration of minor neurological deficits. What is progressing stroke? Stroke. 1983;14:363-8. CrossrefMedlineGoogle Scholar
    • 35. Ramirez-Lassepas M and Quinones M. Heparin therapy for stroke: Hemorrhagic complications and risk factors for intracerebral hemorrhage. Neurology. 1984;34:114-7. CrossrefMedlineGoogle Scholar
    • 36. Ruff R and Dougherty J. Evaluation of acute cerebral ischemia for anticoagulant therapy: computed tomography or lumbar puncture. Neurology. 1981;31:736-40. CrossrefMedlineGoogle Scholar
    • 37. Haley E, Kassell N, and Torner J. Failure of heparin to prevent progression in progressing ischemic infarction. Stroke 1988; 19:10-4. CrossrefMedlineGoogle Scholar
    • 38. Bogousslavsky J and Regli F. Anticoagulant-induced intracerebral bleeding in brain ischemia. Evaluation in 200 patients with TIAs, emboli from the heart, and progressing stroke. Acta Neurol Scand. 1985;71:464-71. CrossrefMedlineGoogle Scholar
    • 39. . Immediate anticoagulation of embolic stroke: a randomized trial. Stroke. 1983;14:668-76. CrossrefMedlineGoogle Scholar
    • 40. . Immediate anticoagulation of embolic stroke: brain hemorrhage and management options. Stroke. 1984;15:779-89. CrossrefMedlineGoogle Scholar
    • 41. Shields R, Laureno R, Lachman T, and Victor M. Anticoagulant-related hemorrhage in acute cerebral embolism. Stroke. 1984; 15:426-37. CrossrefMedlineGoogle Scholar
    • 42. Rothrock J, Dittrich H, McAllen S, Taft B, and Lyden P. Acute anticoagulation of cardioembolic stroke and TIA. Stroke. 1989;20:730-4. CrossrefMedlineGoogle Scholar
    • 43. Biller J, Massey E, Marler J, Adams H, Davis J, and Bruno A. A dose escalation study of ORG 10172 (low molecular weight heparinoid) in the treatment of acute cerebral infarction. Neurology. 1989;39:262-5. CrossrefMedlineGoogle Scholar
    • 44. . Cardioembolic stroke, immediate anticoagulation, and brain hemorrhage. Arch Intern Med. 1987;147:636-40. CrossrefMedlineGoogle Scholar
    • 45. Hart R and Putnam C. Hemorrhagic transformation of cardioembolic stroke [Letter]. Stroke. 1989;20:117. CrossrefGoogle Scholar
    • 46. Hart R and Easton J. Hemorrhagic infarcts. Stroke. 1986;17:586-9. CrossrefMedlineGoogle Scholar
    • 47. Okada Y, Yamaguchi T, Minematsu K, Miyashita T, Sawada T, and Sadoshima S. Hemorrhagic transformation in cerebral embolism. Stroke. 1989;20:598-3. CrossrefMedlineGoogle Scholar
    • 48. Ansell J, Price J, Shah S, and Beckner R. Heparin-induced thrombocytopenia. Chest. 1985;88:878-82. CrossrefMedlineGoogle Scholar
    • 49. Kelton J. Heparin-induced thrombocytopenia. Haemostasis. 1986;16:173-86. MedlineGoogle Scholar
    • 50. Bell W. Heparin-associated thrombocytopenia and thrombosis. J Lab Clin Med. 1988;111:600-5. MedlineGoogle Scholar
    • 51. Rao A, White G, Sherman L, Colman R, Lan G, and Ball A. Low incidence of thrombocytopenia with porcine mucosal heparin. A prospective multicenter study. Arch Intern Med. 1989;149:1285-8. CrossrefMedlineGoogle Scholar
    • 52. Becker P and Miller V. Heparin-induced thrombocytopenia. Stroke. 1989;20:1449-59. CrossrefMedlineGoogle Scholar
    • 53. Chang J. White clot syndrome associated with heparin-induced thrombocytopenia: a review of 23 cases. Heart Lung. 1987; 16:403-7. MedlineGoogle Scholar
    • 54. Phelan B. Heparin-associated thrombosis without thrombocytopenia. Ann Intern Med. 1983;99:637-8. LinkGoogle Scholar
    • 55. Hirsh J, Ofosu F, and Buchanan M. Rationale behind the development of low molecular weight heparin derivatives. Sem Thromb Hemost. 1985;11:13-6. CrossrefMedlineGoogle Scholar
    • 56. Salzman E. Low-molecular-weight heparin. Is small beautiful? [Editorial]. N Engl J Med. 1986;315:957-9. CrossrefMedlineGoogle Scholar
    • 57. Turpie A, Levine M, Hirsh J, Carter C, Jay R, and Powers P. Double-blind randomised trial or Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in patients with thrombotic stroke. Lancet. 1987;1:523-6. CrossrefMedlineGoogle Scholar
    • 58. Green D, Lee M, Lim A, Chmiel J, Vetter M, and Pang T. Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin. Ann Intern Med. 1990;113:571-4. LinkGoogle Scholar
    • 59. Ten Cate H, Henny C, Buller H, Ten Cate J, and Magnani H. Use of heparinoid in patients with hemorrhagic stroke and thromboembolic disease. Ann Neurol. 1984;15:268-70. CrossrefMedlineGoogle Scholar
    • 60. Massey E, Biller J, Davis J, Adams H, Marler J, and Goldstein L. Large-dose infusions of heparinoid ORG 10172 in ischemic stroke. Stroke 1990;21:1289-92. CrossrefMedlineGoogle Scholar
    • 61. Cairns J, Gent M, Singer J, Finnie K, Froggatt G, and Holder D. Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial. N Engl J Med. 1985;313:1369-75. CrossrefMedlineGoogle Scholar
    • 62. Lewis H, David J, Archibald D, Steinke W, Smitherman T, and Doherty J. 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. CrossrefMedlineGoogle Scholar
    • 63. . Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-60. MedlineGoogle Scholar
    • 64. Zeumer H, Hacke W, and Ringelstein E. Local intraarterial thrombolysis in vertebrobasilar thromboembolic disease. AJNR. 1983;4:401-4. MedlineGoogle Scholar
    • 65. Zeumer H, Hundgen R, Ferbert A, and Ringelstein E. Local intraarterial fibrinolytic therapy in inaccessible internal carotid occlusion. Neuroradiology. 1984;26:315-7. CrossrefMedlineGoogle Scholar
    • 66. Guerci A, Gerstenblith G, Brinker J, Chandra N, Gottlieb S, and Bahr R. A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. N Engl J Med. 1987;317:1613-8. CrossrefMedlineGoogle Scholar
    • 67. del Zoppo G, Ferbert A, Otis S, Bruckman H, Hacke W, and Zyroff J. Local intra-arterial fibrinolytic therapy in acute carotid territory stroke. A pilot study. Stroke. 1988;19:307-13. CrossrefMedlineGoogle Scholar
    • 68. del Zoppo G. Investigational use of tPA in acute stroke. Ann Emerg Med. 1988;17:1196-201. CrossrefMedlineGoogle Scholar
    • 69. Zivin J. Thrombolytic therapy for stroke. In: Weinstein PR, Faden AI, eds. Protection of the Brain From Ischemia. Baltimore, Maryland: Williams & Wilkens; 1990:231-6. Google Scholar
    • 70. Brott T, Haley C, Levy D, Barsan S, Sheppard G, and Broderick J. Safety and potential efficacy of tissue plasminogen activator (tPA) for stroke [Abstract]. Stroke. 1990;21:27. Google Scholar
    • 71. . An open multicenter study of the safety and efficacy of various closes of tPA in patients with acute stroke: a progress report [Abstract]. Stroke. 1990;21:27. Google Scholar
    • 72. . An open safety/efficacy trial of rt-PA in acute thromboembolic stroke: final report [Abstract]. Stroke. 1991;22:153. Google Scholar
    • 73. Koudstaal P, Stibbe J, and Vermeulen M. Fatal ischaemic brain edema after early thrombolysis with tissue plasminogen activator in acute stroke. BMJ. 1988;297:1571-4. CrossrefMedlineGoogle Scholar
    • 74. Hossman V, Heiss W, Bewermeyer H, and Wiedemann G. Controlled trial of ancrod in ischemic stroke. Arch Neurol. 1983;40:803-8. CrossrefMedlineGoogle Scholar
    • 75. Olinger C, Brott T, Barsan W, Hedges J, and Glas-Greenwalt P. Double-blind, randomized placebo controlled study of ancrod as therapy for acute cerebral infarction. Stroke. 1988;17:133. Google Scholar
    • 76. Pollak V, Glas-Greenwalt P, Olinger C, Wadhwa N, and Myre S. Ancrod causes rapid thrombolysis in patients with acute stroke. Am J Med Sci. 1990;299:319-25. CrossrefMedlineGoogle Scholar
    • 77. Bogousslavsky J, van Melle G, Regli F, and Kappenberger L. Causes of stroke in patients with non-valvular atrial fibrillation. Stroke. 1990;21:20. Google Scholar
    • 78. . Cardiogenic brain embolism: The second report of the Cerebral Embolism Task Force. Arch Neurol. 1989;46:727-43. CrossrefMedlineGoogle Scholar
    • 79. . Cardiogenic brain embolism. Arch Neurol. 1986;43:71-84. CrossrefMedlineGoogle Scholar
    • 80. Norrving B and Nilsson B. Cerebral embolism of cardiac origin; the limited possibilities of secondary prevention [Abstract]. Acta Neurol Scand. 1986;73:520. Google Scholar
    • 81. Hart R, Coull B, and Hart D. Early recurrent embolism associated with nonvalvular atrial fibrillation. Stroke. 1983;14:688-93. CrossrefMedlineGoogle Scholar
    • 82. Santamaria J, Graus F, and Peres J. Cerebral embolism and anticoagulation [Letter]. Neurology. 1983;33:1104. CrossrefGoogle Scholar
    • 83. Fisher C. Embolism in atrial fibrillation. In: Kulbertus HE, Olsson SB, Schlepper M, eds. Atrial Fibrillation. Molndal, Sweden: A.B. Hassle; 1982:192-205. Google Scholar
    • 84. Sage J. Prospective study of stroke associated with nonvalvular atrial fibrillation: low frequency of early recurrence [Abstract]. Ann Neurol. 1986;20:155. Google Scholar
    • 85. Yamanouchi H, Nagura H, Ohkawa Y, Sakurai Y, Kuzuhara S, and Kuramoto K. Anticoagulant therapy in recurrent cerebral embolism: a retrospective study in nonvalvular atrial fibrillation. J Neurol. 1988;235:407-10. CrossrefMedlineGoogle Scholar
    • 86. Broderick J, Phillips S, O'Fallon W, and Whisnant J. Heart disease as a potential cause of stroke. Stroke. 1990;21:19. Google Scholar
    • 87. McIlraith D, Cote R, and Wolson C. Acute cerebral infarction in non-valvular atrial fibrillation: early recurrence of stroke and other ischemic events. Stroke. 1990;21:20. Google Scholar
    • 88. Toole J. Cerebrovascular Disorders. New York: Raven Press; 1984:187. Google Scholar
    • 89. Hornig C, Dorndorf W, and Agnoli A. Hemorrhagic cerebral infarction—a prospective study. Stroke. 1986;17:179-85. CrossrefMedlineGoogle Scholar
    • 90. . Timing of hemorrhagic transformation of cardioembolic stroke. In: Stober T, Shimrigk K, Ganten D, Sherman DG, eds. Central Nervous System Control of the Heart. Boston: Martinus Nijhoff Publishing; 1986:229-32. Google Scholar
    • 91. Sato Y, Mizoguchi K, Sato Y, Ohkita Y, and Kaji M. Anticoagulant and thrombolytic therapy for cerebral embolism of cardiac origin. Kurume Med J. 1986;33:89-95. CrossrefMedlineGoogle Scholar
    • 92. Lodder J, Krijne-Kubat B, and van der Lugt P. Timing of autopsy-confirmed hemorrhagic infarction with reference to cardioembolic stroke. Stroke. 1988;19:1482-4. CrossrefMedlineGoogle Scholar
    • 93. Carter A. Anticoagulant treatment in progressing stroke. Br Med J. 1961;2:70-3. CrossrefMedlineGoogle Scholar
    • 94. Baker R, Broward J, Fang H, Fisher C, Groch S, and Heyman A. Anticoagulant therapy in cerebral infarction. Neurology. 1962;12:823-35. CrossrefMedlineGoogle Scholar
    • 95. Fisher C. Use of anticoagulants in cerebral thrombosis. Neurology. 1958;8:311-32. CrossrefMedlineGoogle Scholar
    • 96. Fisher C. Anticoagulant therapy in cerebral thrombosis and cerebral embolism: a national cooperative study. Interim report. Neurology. 1961;11:132-8. CrossrefMedlineGoogle Scholar
    • 97. Whisnant J, Matsumoto N, and Elveback L. Transient cerebral ischemic attacks in a community. Rochester, Minnesota 1955 through 1969. Mayo Clin Proc. 1973;48:194-8. MedlineGoogle Scholar
    • 98. Donnan G and Bladin P. Capsular warning syndrome: repetitive hemiplegia preceding capsular stroke [Abstract]. Stroke. 1987;18:296. Google Scholar
    • 99. Rothrock J, Lyden P, Yee J, and Wiederholt W. Unstable carotid artery syndrome: clinical management, risks and outcome. Vasc Surg. 1987;21:248-56. CrossrefGoogle Scholar
    • 100. Moster M, Johnston D, and Reinmuth O. Chronic subdural hematoma with transient neurological deficits: a review of 15 cases. Ann Neurol. 1983;14:539-42. CrossrefMedlineGoogle Scholar
    • 101. Easton J, Hart R, Sherman D, and Kaste M. Diagnosis and management of ischemic stroke. Part I. Threatened stroke and its management. Curr Probl Cardiol. 1983;8:1-76. CrossrefGoogle Scholar
    • 102. . Beneficial effect of carotid endarterectomy in symptomatic patients with high grade carotid stenosis. N Engl J Med. 1991;325:445-53. CrossrefMedlineGoogle Scholar
    • 103. Brody M, Lyden P, Clark W, and Rothrock J. First year stroke recurrence rates amongst ischemic stroke subtypes [Abstract]. Neurology. 1991;41(Suppl 1):126. Google Scholar
    • 104. Borstein N, Waksman O, and Korczyn A. The relative weight of risk factors (RF) for recurrent strokes [Abstract]. Neurology. 1991;41(Suppl 1):328. Google Scholar
    • 105. Whisnant J, Matsumoto N, and Elveback L. The effect of anticoagulant therapy on the prognosis of patients with transient cerebral ischemic attacks in a community. Mayo Clin Proc. 1973;48:844-8. MedlineGoogle Scholar
    • 106. Jonas S. Anticoagulant therapy in cerebrovascular disease: review and meta-analysis. Stroke. 1988;19:1043-8. CrossrefMedlineGoogle Scholar
    • 107. Olsson J, Brechter C, Backlund H, Krook H, Muller R, and Nitelius E. Anticoagulant vs. antiplatelet therapy as prophylactic against cerebral infarction in transient ischemic attacks. Stroke. 1980;11:4-9. CrossrefMedlineGoogle Scholar
    • 108. Buren A and Ygge J. Treatment program and comparison between anticoagulants and platelet aggregation inhibitors after transient ischemic attack. Stroke. 1981;12:578-80. CrossrefMedlineGoogle Scholar
    • 109. Garde A, Samuelsson K, Fahlgran H, Hedberg E, Hjerne L, and Ostman J. Treatment after transient ischemic attacks: A comparison between anticoagulant drug and inhibition of platelet aggregation. Stroke. 1983;14:677-81. CrossrefMedlineGoogle Scholar
    • 110. Craven L. Acetylsalicylic acid, possible preventative of coronary thrombosis [Letter]. Ann Western Med Surg. 1950;4:95-9. MedlineGoogle Scholar
    • 111. Fields W, Lemak N, Frankowski R, and Hardy R. Controlled trial of aspirin in cerebral ischemia. Stroke. 1977;8:301-14. CrossrefMedlineGoogle Scholar
    • 112. . A randomized trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med. 1978;299:53-9. CrossrefMedlineGoogle Scholar
    • 113. Candelise L, Landi G, Perrane P, Bracchi M, and Brambilla G. A randomized trial of aspirin and sulfinpyrazone in patients with TIA. Stroke. 1982;13:175-9. CrossrefMedlineGoogle Scholar
    • 114. Bousser M, Eschwege E, Haguenau M, Lefauczonnier J, Thibult N, and Touboul D. "AICLA" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke. 1983;14:5-14. CrossrefMedlineGoogle Scholar
    • 115. Sorensen P, Pedersen H, Marquardsen J, Petersson H, Heltberg A, and Simonsen N. Acetylsalicylic acid in the prevention of stroke in patients with reversible cerebral ischemic attacks. Stroke. 1983;14:15-22. CrossrefMedlineGoogle Scholar
    • 116. . High-dose acetylsalicylic acid after cerebral infarction. Stroke. 1987;18:325-34. CrossrefMedlineGoogle Scholar
    • 117. . United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results. Br Med J [Clin Res]. 1988;296:316-20. CrossrefMedlineGoogle Scholar
    • 118. . The European Stroke Prevention Study. Stroke. 1990;21:1122-30. CrossrefMedlineGoogle Scholar
    • 119. . Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J 1988;296:320-31. CrossrefMedlineGoogle Scholar
    • 120. . Persantine Aspirin Trial in cerebral ischemia. Part II. Endpoint results. Stroke. 1985;16:406-15. CrossrefMedlineGoogle Scholar
    • 121. Harris W, Salzman E, Athansoulis C, Waltman A, and DeSanctis R. Aspirin prophylaxis of venous thromboembolism after total hip replacement. N Engl J Med. 1977;297:1246-8. CrossrefMedlineGoogle Scholar
    • 122. Kelton J, Hirsh J, Carter C, and Buchanan M. Sex differences in the antithrombotic effects of aspirin. Blood. 1978;52:1073-6. CrossrefMedlineGoogle Scholar
    • 123. Barnett H. Stroke prevention and treatment: milestones, perspectives and challenges. In: Plum F, Pusinelli W, eds. Cerebrovascular Diseases 14th Research (Princeton) Conference. New York: Raven Press; 1985:27. Google Scholar
    • 124. Dyken M. Antiplatelet aggregating agents in transient ischemic attacks and the relationship of risk factors. In: Breddin K, et al., eds. Prophylaxis of Venous, Peripheral, Cardiac, and Cerebral Vascular Diseases with Acetylsalicylic Acid. New York: F.K. Schattauer Verlag; 1981;141. Google Scholar
    • 125. . The Dutch TIA Trial: protective effects of low-dose aspirin and atenolol in patients with transient ischemic attack or nondisabling stroke. Stroke. 1988;19:512-7. CrossrefMedlineGoogle Scholar
    • 126. Hass W, Easton J, Adams H, Pryse-Phillips W, Molony B, and Anderson S. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med. 1989;321:501-7. CrossrefMedlineGoogle Scholar
    • 127. Gent M, Blakely J, Easton J, Ellis D, Hachinski V, and Harbison J. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet. 1989;1215-20. CrossrefMedlineGoogle Scholar
    • 128. Petersen P, Boysen G, Godtfredsen J, Andersen E, and Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. Lancet. 1989;1:175-9. CrossrefMedlineGoogle Scholar
    • 129. . Preliminary report of the Stroke Prevention in Atrial Fibrillation Study. N Engl J Med. 1990;322:863-8. CrossrefMedlineGoogle Scholar
    • 130. . Stroke Prevention in Atrial Fibrillation Study: final results. Circulation. 1991;84:527-39. CrossrefMedlineGoogle Scholar
    • 131. Connally S, Laupaucis A, Gent M, Roberts R, and Cairns J. Canadian Atrial Fibrillation Anticoagulation Study [Abstract]. Circulation. 1990;82 (Suppl 3):108. Google Scholar
    • 132. . The effect of low-dose warfarin on the risk of stroke in nonrheumatic atrial fibrillation. N Engl J Med. 1990;323:1505-11. CrossrefMedlineGoogle Scholar
    • 133. Shi F, Hart R, Sherman D, and Tegeler C. Stroke in the Peoples Republic of China. Stroke 1989;20:1581-5. CrossrefMedlineGoogle Scholar
    • 134. Kopecky S, Gersh B, McGoon M, Whisnant J, Holmes D, Ilstrup D, and Frye R. The natural history of lone atrial fibrillation. A population-based study over three decades. N Engl J Med. 1987;317:669-74. CrossrefMedlineGoogle Scholar
    • 135. Sherman D, Hart R, and Easton J. The secondary prevention of stroke in patients with atrial fibrillation. Arch Neurol. 1986;43:68-70. CrossrefMedlineGoogle Scholar
    • 136. Wintzen A, de Jonge H, Loeliger E, and Bots G. The risk of intracerebral hemorrhage during oral anticoagulant treatment: a population study. Ann Neurol. 1984;16:553-8. CrossrefMedlineGoogle Scholar
    • 137. Miller V, Cohen B, Feinberg W, and Rothrock J. Strokes in patients with nonvalvular atrial fibrillation [Abstract]. Circulation. 1989:80(Suppl II):404. Google Scholar
    • 138. Smith P, Arnesen H, and Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med. 1990;323:147-52. CrossrefMedlineGoogle Scholar
    • 139. . Prevention of vascular events by antiplatelet treatment. The second report. BMJ. 1991; [In press]. Google Scholar
    • 140. Peto R, Gray R, Collins R, Wheatley K, Hennekens C, and Jamrozik K. Randomised trial of prophylactic daily aspirin among British male doctors. Br Med J [Clin Res]. 1988;296:313-6. CrossrefMedlineGoogle Scholar
    • 141. . Final report on the aspirin component of the ongoing physicians' health study. N Engl J Med. 1989;321:130-5. Google Scholar

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