Drugs

, Volume 45, Issue 3, pp 329–337 | Cite as

Prophylaxis and Treatment of Stroke

The State of the Art in 1993
  • Cathy A. Sila
Review Article

Summary

The most significant impact on cerebral infarction comes from the primary prevention of the processes that lead to stroke in at-risk individuals prior to the development of symptoms. Antithrombotic therapy with warfarin or aspirin significantly reduces thromboembolic risk in non-valvular atrial fibrillation. The failure of primary preventive measures and the progression of disease is heralded by the development of cerebral or retinal ischaemic events; the majority of clinical trials investigating stroke prevention have targeted the secondary prevention of stroke in patients with ischaemic symptoms. A 25% risk reduction has been demonstrated with antiplatelet therapy. This was typically aspirin 1000 to 1300 mg/day, but more recently even lower doses have been beneficial, with lower rates of minor and major bleeding.

Ticlopidine has demonstrated efficacy in the secondary prevention of stroke after transient ischaemic attacks and completed stroke, with a 2% risk of significant neutropenia.

The benefits of carotid endarterectomy have been demonstrated in patients with symptomatic internal carotid artery stenosis involving 70 to 99% of the arterial diameter. Surgery is not indicated in patients with less than 3.0% internal carotid artery stenosis; 30 to 69% continues to be studied.

When primary and secondary preventive measures have failed, strategies directed at managing acute focal cerebral ischaemia include re-establishing cerebral blood flow and limiting ischaemic neuronal injury. Advances in basic research that have identified components of the ischaemic cascade have been translated clinically into numerous clinical trials, each targeted to one or sometimes two steps in the hope of improving neuronal salvage. Because of the complex intracellular and extracellular processes evolving during ischaemia, it is naive to expect that a single drug directed toward one component of this cascade will provide dramatic results and thus far many trials have had minimal or negative results.

Keywords

Atrial Fibrillation Cerebral Infarction Nimodipine Carotid Endarterectomy Transient Ischaemic Attack 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams Jr HP, Woolson RF. Clinical trials in acute ischemic stroke: problems in design and interpretation. Journal of Stroke and Cerebrovascular Diseases 1: 134–141, 1991CrossRefGoogle Scholar
  2. Albers GW, Goldberg MP, Choi DW. N-methyl-D-asparate antagonists: ready for clinical trial in brain ischemia?. Annals of Neurology 25: 398–403, 1989PubMedCrossRefGoogle Scholar
  3. Albers GW, Sherman DG, Gress DR, Paulseth JE, Peterson P. Stroke prevention in nonvalvular atrial fibrillation; a review of prospective randomized trials. Annals of Neurology 30: 511–518, 1991PubMedCrossRefGoogle Scholar
  4. American Nimodipine Study Group. Clinical trial of nimodipine in acute ischemic stroke. Stroke 23: 3–8, 1992CrossRefGoogle Scholar
  5. Antiplatelet Trialists’ Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet treatment. British Medical Journal 296: 320–331, 1988CrossRefGoogle Scholar
  6. Argentino C, Sacchetti ML, Toni D, Savoini G, D’Arcangelo E, et al. GM1 ganglioside therapy in acute ischemie stroke. Stroke 20: 1143–1149, 1989PubMedCrossRefGoogle Scholar
  7. Asplund K. Randomized clinical trials of hemodilution in acute ischemie stroke. Acta Neurologica Scandinavica 127: 22–30, 1989PubMedCrossRefGoogle Scholar
  8. Asymptomatic Carotid Atherosclerosis Study Group. Study design for randomized prosepctive trial of carotid endarterectomy for asymptomatic atherosclerosis. Stroke 20: 844–849, 1989CrossRefGoogle Scholar
  9. Asymptomatic Cervical Bruit Study Group. Natural history and effectiveness of aspirin in asymptomatic patients with cervical bruits. Archives of Neurology 48: 683–686, 1991CrossRefGoogle Scholar
  10. Bogousslavsky J, Regli F, Zumstein V, Kobberling W. Double-blind study of nimodipine in non-severe stroke. European Neurology 30: 23–26, 1990PubMedCrossRefGoogle Scholar
  11. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with non-rheumatic atrial fibrillation. New England Journal of Medicine 323: 1505–1511, 1990CrossRefGoogle Scholar
  12. Bousser MG, Eschwege E, Haguenau M, LaFucconnier JM, Thibult N, et al., AICLA, controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischemia. Stroke 14: 5–14, 1983PubMedCrossRefGoogle Scholar
  13. Braune S. Is ganglioside GM1 effective in the treatment of stroke?. Drugs & Aging 1: 57–66, 1991CrossRefGoogle Scholar
  14. Brott TG, Haley EC, Levy DE, Barsan W, Broderick J, et al. Urgent therapy for stroke. Part I. Pilot study of tissue plas-minogen activator administered within 90 minutes. Stroke 23: 632–640, 1992Google Scholar
  15. Buchan AM. Do NMDA antagonists protect against cerebral ischemia: are clinical trials warranted?. Cerebrovascular and Brain Metabolism Reviews 2: 1–26, 1990PubMedGoogle Scholar
  16. CASANOVA Study Group. Carotid surgery versus medical therapy in asymptomatic carotid stenosis. Stroke 22: 1229–1235, 1991CrossRefGoogle Scholar
  17. Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. New England Journal of Medicine 315: 860–865, 1986PubMedCrossRefGoogle Scholar
  18. Connally SJ, Laupacis A, Gent M, Roberts RS, Cairus JA. Canadian Atrial Fibrillation Anticoagulation (CAFA) study. Journal of the American College of Cardiology 18: 349–355, 1991CrossRefGoogle Scholar
  19. Del Zoppo GJ, Pessin MS, Mori E, Hacke N. Thrombolytic intervention in acute thrombotic and embolie stroke. Seminars in Neurology 11: 368–384, 1991PubMedCrossRefGoogle Scholar
  20. Del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolie stroke. Annals of Neurology 32: 78–86, 1992PubMedCrossRefGoogle Scholar
  21. Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30mg vs 283mg a day) in patients after a transient ischemie attack or minor ischemic stroke. New England Journal of Medicine 325: 1261–1266, 1991CrossRefGoogle Scholar
  22. ESPS Group. European Stroke Prevention Study. Stroke 21: 1122–1130, 1990CrossRefGoogle Scholar
  23. European Carotid Surgery Trialists Collaborative Group. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70–90%) or with mild (0–29%) carotid stenosis. Lancet 337: 1235–1243, 1991CrossRefGoogle Scholar
  24. Gelmers HJ, Gorter K, de Weerdt CJ, Wiezer HJ. A controlled trial of nimodipine in acute ischemic stroke. New England Journal of Medicine 318: 203–207, 1988PubMedCrossRefGoogle Scholar
  25. Gent M, Blakely JA, Easton JD, Ellis DJ, Hachinski VC, et al. The Canadian American Ticlopidine Study (CATS) in throm-boembolic stroke. Lancet 1: 1215–1220, 1989PubMedCrossRefGoogle Scholar
  26. Giraldi C, Masi MC, Manetti M, Carabelli E, Martini A. A pilot study with monosialoganglioside GM1 on acute cerebral ischemia. Acta Neurologica 12: 214–221, 1990PubMedGoogle Scholar
  27. Hakim AM, Evans AC, Berger L, Kuwabara H, Worsley K, et al. The effect of nimodipine on the evolution of human cerebral infarction studied by PET. Journal of Cerebral Blood Flow and Metabolism 9: 523–534, 1989PubMedCrossRefGoogle Scholar
  28. Haley EC, Levy DE, Brott TG, Sheppard GL, Wong MCW, et al. Urgent therapy for stroke. Part II. Pilot study of tissue plasminogen activator administered 91–180 minutes from onset. Stroke 23: 641–645, 1992Google Scholar
  29. Hass WK, Easton JD, Adams HJ, Pryse-Phillips W, Molony BA, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. New England Journal of Medicine 321: 501–507, 1989PubMedCrossRefGoogle Scholar
  30. Hemodilution in Stroke Study Group. Hypervolemic hemodilution treatment of acute stroke. Results of a randomized multicenter trial using pentastarch. Stroke 20: 317–323, 1989CrossRefGoogle Scholar
  31. Hsu CY, Faughtd RE, Furlan AJ, Coult BM, Huang DC, et al. Intravenous prostacyclin in acute nonhemorrhagic stroke. Stroke 18: 352–358, 1987PubMedCrossRefGoogle Scholar
  32. Hsu CY, Norris JW, Hogan EL, Bladin P, Dinsdale HT, et al. Pentoxifylline in acute nonhemorrhagic stroke. A randomized, placebo-controlled double-blind trial. Stroke 19: 716–722, 1988PubMedCrossRefGoogle Scholar
  33. Italian Acute Stroke Study Group. Haemodilution in acute stroke: results of the Italian haemodilution trial. Lancet 1: 318–321, 1988Google Scholar
  34. Jones S. Anticoagulant therapy in cerebrovascular disease: review and meta-analysis. Stroke 19: 1043–1048, 1988CrossRefGoogle Scholar
  35. Lake FR, Thompson PL. Prevention of embolie complications in nonvalvular atrial fibrillation in the elderly. Drugs & Aging 1: 458–466, 1991CrossRefGoogle Scholar
  36. Marmot MG, Poulter NR. Primary prevention of stroke. Lancet 339: 344–347, 1992PubMedCrossRefGoogle Scholar
  37. Martin JF, Hamdy N, Nicholl J, Lewtas N, Bergval U, et al. Double-blind controlled trial of prostacyclin in cerebral infarction. Stroke 16: 386–390, 1985PubMedCrossRefGoogle Scholar
  38. Martinez-Vila E, Guillen F, Villanueva JA, Matias-Guiu J, Bigorra J, et al. Placebo-controlled trial of nimodipine in the treatment of acute ischemie cerebral infarction. Stroke 21: 1023–1028, 1990PubMedCrossRefGoogle Scholar
  39. Mayberg MR, Wilson SE, Yatsu F. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Journal of the American Medical Association 266: 3289–3294, 1991PubMedCrossRefGoogle Scholar
  40. NASCET Investigators. Clinical alert: benefit of carotid endarterectomy for patients with high-grade stenosis of the internal carotid artery. Stroke 22: 816–817, 1991CrossRefGoogle Scholar
  41. Norris JS, Hachinski VC. High dose steroid treatment in cerebral infarction. British Medical Journal 292: 21–23, 1986PubMedCrossRefGoogle Scholar
  42. Norris JW, Zhu CZ, Bornstein NM, Chambers BR. Vascular risks of asymptomatic carotid stenosis. Stroke 22: 1485–1490, 1991PubMedCrossRefGoogle Scholar
  43. Olinger CP, Brott TG, Barsan WG, Hedges JR, Glas-Greenwalt P, et al. Use of ancrod in acute or progressing ischemic cerebral infarction. Annals of Emergency Medicine 17: 1208–1209, 1988PubMedCrossRefGoogle Scholar
  44. Paci A, Ottaviiano P, Trenta A, Iannone G, DeSantis L, et al. Nimodipine in acute ischemic stroke: a double-blind controlled study. Acta Neurologica Scandinavica 80: 282–286, 1989PubMedCrossRefGoogle Scholar
  45. Peterson P, Godtfredsen J, Boysen G, Andersen ED, Andersen B. Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study. Lancet 1: 175–179, 1989CrossRefGoogle Scholar
  46. Sacco RL, Ellenberg JH, Mohr JP, Tatemichi TK, Hier DB, et al. Infarction of undetermined cause: the NINCDS stroke data bank. Annals of Neurology 25: 382–390, 1989PubMedCrossRefGoogle Scholar
  47. SALT Collaborative Group. Swedish Aspirin Low-dose Trial (SALT) of 75mg aspirin as secondary prophylaxis after cere-brovascular ischaemic events. Lancet 338: 1345–1349, 1991CrossRefGoogle Scholar
  48. Solis OJ, Roberson GR, Taveras JM, Mohr J, Pessin MS. Cerebral angiography in acute cerebral infarction. Revista Intera-mericana Radiologia 2: 19–25, 1977Google Scholar
  49. Special Report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular disease III. Stroke 21: 637–676, 1990CrossRefGoogle Scholar
  50. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing physician’s health study. New England Journal of Medicine 321: 129–135, 1989CrossRefGoogle Scholar
  51. Stroke Prevention in Atrial Fibrillation Investigators. The stroke prevention in atrial fibrillation study: final results. Circulation 84: 527–539, 1991CrossRefGoogle Scholar
  52. Stroke Prevention in Atrial Fibrillation Investigators. Preliminary report of the stroke prevention in atrial fibrillation study. New England Journal of Medicine 322: 863–868, 1990Google Scholar
  53. Toole JF. The Willis lecture: transient ischemic attacks, scientific method, and new realities. Stroke 22: 99–104, 1991PubMedCrossRefGoogle Scholar
  54. Towne JB, Weiss DG, Hobson II RW. First phase report of cooperative veterans administration asymptomatic carotid stenosis study: operative morbidity and mortality. Journal of Vascular Surgery 11: 252–259, 1990PubMedGoogle Scholar
  55. UK-TIA Study Group. United Kingdom transient ischemic attack (UK-TIA) aspirin trial: interim results. British Medical Journal 296: 316–320, 1988CrossRefGoogle Scholar
  56. Wadworth AN, McTavish D. Nimodipine. A review of its pharmacological properties and therapeutic efficacy in cerebral disorders. Drugs & Aging 2: 262–286, 1992CrossRefGoogle Scholar
  57. Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and the risk of stroke: the Framingham Study. Neurology 28: 973–977, 1978PubMedCrossRefGoogle Scholar
  58. Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham Study. Stroke 22: 312–318, 1991PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • Cathy A. Sila
    • 1
  1. 1.Cerebrovascular Program, Department of NeurologyCleveland Clinic Foundation, One Clinic CenterClevelandUSA

Personalised recommendations