CNS Drugs

, Volume 18, Issue 4, pp 221–241

Secondary Prevention of Stroke

A Practical Guide to Drug Treatment
Therapy in Practice

Abstract

Stroke is a disease of the elderly and, as a result of the expected demographic changes in many industrialised countries, its incidence is likely to increase in the future. A first-ever stroke significantly increases the likelihood of further events; thus, secondary prevention is of major importance. Only a minority of recurrent strokes can be prevented by surgical or other invasive methods, meaning that most secondary preventive measures involve drug treatment, which has become increasingly sophisticated in recent years.

Ischaemic stroke constitutes the vast majority of all strokes; effective secondary prevention depends on a variety of factors, of which the correct classification in terms of subtypes and aetiological mechanisms is a pivotal prerequisite, as is the assessment of the patient’s cardiovascular risk profile. In addition to the evaluation of pathomechanisms, stratification of subtypes of brain infarction is mainly based on morphology seen with brain imaging techniques, which provides additional evidence for the presumed cause of the stroke.

Inhibitors of platelet function and anticoagulants are the two major groups of antithrombotic drugs used for the secondary prevention of stroke. Antiplatelet agents are still indicated in the majority of patients after ischaemic stroke, especially if an arterial origin is presumed. In addition to aspirin (acetylsalicylic acid), the position of which as the first-line antiplatelet drug is increasingly being questioned, other compounds with antiplatelet activity have been developed and have proven effective in secondary stroke prevention, including ticlopidine, clopidogrel and dipyridamole. Anticoagulants are principally indicated after cardioembolic ischaemic stroke; however, their inherent bleeding risks render their use in many cases rather difficult, in particular for elderly patients. Patient compliance with the recommended treatment is of major importance, given the somewhat limited efficacy of antithrombotic agents in stroke prevention. Since ‘real world’ experience does not match the circumstances under which clinical trials are conducted, this article will also deal with problems not covered by specific studies, such as risk stratification for anticoagulant treatment and how to proceed in cases of unknown stroke aetiology.

The management of major cardiovascular risk factors is the other mainstay of secondary stroke prevention. Recent evidence indicates that antihypertensive treatment may be as effective as antithrombotic drugs for secondary prevention of stroke. This still needs to be proven for the treatment of other cardiovascular risk factors, such as diabetes mellitus and hypercholesterolemia. Nevertheless, the results of recent studies investigating the effect of HMG-CoA reductase inhibitors (‘statins’) on cardiovascular events strongly suggest a stroke-preventive effect.

References

  1. 1.
    WHO. World Health Report 1999. Geneva: WHO, 1999Google Scholar
  2. 2.
    Bonita R. Epidemiology of stroke. Lancet 1992; 339: 342–4PubMedCrossRefGoogle Scholar
  3. 3.
    Kolominsky-Rabas PL, Sarti C, Heuschmann PU, et al. A prospective community-based study of stroke in Germany: The Erlangen Stroke Project (ESPro): incidence and case fatality at 1, 3, and 12 months. Stroke 1998; 29: 2501–6PubMedCrossRefGoogle Scholar
  4. 4.
    Thorvaldsen P, Asplund K, Kuulasmaa K, et al. Stroke incidence, case fatality, and mortality in the WHO MONICA project: World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease. Stroke 1995; 26(3): 361–7PubMedCrossRefGoogle Scholar
  5. 5.
    Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001; 119: 300S–20SPubMedCrossRefGoogle Scholar
  6. 6.
    Wolf PA, Clagett GP, Easton JD, et al. Preventing ischemic stroke in patients with prior stroke and transient ischemic attack: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke 1999; 30: 1991–4PubMedCrossRefGoogle Scholar
  7. 7.
    Grau A, Weimar C, Buggle F, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: The German Stroke Data Bank. Stroke 2001; 32: 2559–66PubMedCrossRefGoogle Scholar
  8. 8.
    Moncayo J, Devuyst G, van Melle G, et al. Coexisting causes of ischemic stroke. Arch Neurol 2000; 57: 1139–44PubMedCrossRefGoogle Scholar
  9. 9.
    Woo D, Sauerbeck LR, Kissela BM, et al. Genetic and environmental risk factors for intracerebral hemorrhage: preliminary results of a population-based study. Stroke 2002; 33: 1190–6PubMedCrossRefGoogle Scholar
  10. 10.
    Muuronen A, Katse M. Outcome of 314 patients with transient ischemic attacks. Stroke 1982; 13: 24–31PubMedCrossRefGoogle Scholar
  11. 11.
    Benavente O, Eliasziw M, Streifler JY, North American Symptomatic Carotid Endarterectomy Trial Collaborators, et al. Prognosis after transient monocular blindness associated with carotid-artery stenosis. N Engl J Med 2001; 345(15): 1084–90PubMedCrossRefGoogle Scholar
  12. 12.
    Donders RC, Dutch TMB Study Group. Clinical features of transient monocular blindness and the likelihood of atherosclerotic lesions of the internal carotid artery. J Neurol Neurosurg Psychiatry 2001; 71(2): 247–9PubMedCrossRefGoogle Scholar
  13. 13.
    Predictors of major vascular events in patients with transient ischemic attack or non-disabling stroke: the Dutch TIA Trial Study Group. Stroke 1993; 24(4): 527–31PubMedCrossRefGoogle Scholar
  14. 14.
    Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24(1): 35–41Google Scholar
  15. 15.
    Mead GE, Lewis SC, Wardlaw JM, et al. Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders? J Neurol 2002; 249: 266–71PubMedCrossRefGoogle Scholar
  16. 16.
    Wiszniewska M, Devuyst G, Bogousslavsky J, et al. What is the significance of leukoaraiosis in patients with acute ischemic stroke? Arch Neurol 2000; 57: 967–73PubMedCrossRefGoogle Scholar
  17. 17.
    Burn J, Dennis M, Bamford J, et al. Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke 1994; 25: 333–7PubMedCrossRefGoogle Scholar
  18. 18.
    Kolominsky-Rabas PL, Weber M, Gefeller O, et al. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke 2001; 32: 2735–40PubMedCrossRefGoogle Scholar
  19. 19.
    Sacco RL, Foulkes MA, Mohr JP, et al. Determinants of early recurrence of cerebral infarction: The Stroke Data Bank. Stroke 1989; 20: 983–9PubMedCrossRefGoogle Scholar
  20. 20.
    Moroney JT, Bagiella E, Paik MC, et al. Risk factors for early recurrence after ischemic stroke: the role of stroke syndrome and subtype. Stroke 1998; 29: 2118–24PubMedCrossRefGoogle Scholar
  21. 21.
    Jørgensen HS, Nakayama H, Reith J, et al. Stroke recurrence: predictors, severity, and prognosis: the Copenhagen Stroke Study. Neurology 1997; 48: 891–5PubMedCrossRefGoogle Scholar
  22. 22.
    Guidelines for the management of transient ischemic attacks: from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks of the Stroke Council of the American Heart Association. Stroke 1994; 25(6): 1320–35CrossRefGoogle Scholar
  23. 23.
    Sacco RL. Risk factors, outcomes, and stroke subtypes for ischemic stroke. Neurology 1997; 49Suppl. 4: S39–44PubMedCrossRefGoogle Scholar
  24. 24.
    Johnston SC, Grees DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000; 284: 2901–6PubMedCrossRefGoogle Scholar
  25. 25.
    Yamamoto H, Bogousslavsky J. Mechanisms of second and further strokes. J Neurol Neurosurg Psychiatry 1998; 64: 771–6PubMedCrossRefGoogle Scholar
  26. 26.
    Toole JF, Yuson CP, Janeway R, et al. Transient ischemic attacks: a prospective study of 225 patients. Neurology 1978; 28: 746–53PubMedCrossRefGoogle Scholar
  27. 27.
    Heyman A, Wilkinson WE, Hurwitz BJ, et al. Risk of ischemic heart disease in patients with TIA. Neurology 1984; 34: 626–30PubMedCrossRefGoogle Scholar
  28. 28.
    Lee KS, Davis Jr CH. Stroke, myocardial infarction, and survival during long-term follow-up after carotid endarterectomy. Surg Neurol 1989; 31: 113–9PubMedCrossRefGoogle Scholar
  29. 29.
    Petty GW, Brown RD, Whisnant JP, et al. Survival and recurrence after first cerebral infarction: a population-based study in Rochester, Minnesota, 1975 through 1989. Neurology 1998; 50: 208–16PubMedCrossRefGoogle Scholar
  30. 30.
    Albers GW. Choice of endpoints in antiplatelet trials: which outcomes are most relevant to stroke patients? Neurology 2000; 54: 1022–8PubMedCrossRefGoogle Scholar
  31. 31.
    Saxena R, Lewis S, Berge E, et al. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial. Stroke 2001; 32(10): 2333–7PubMedCrossRefGoogle Scholar
  32. 32.
    Hart RG, Pallacio S, Pearce LA. Atrial fibrillation, stroke, and acute antithrombotic therapy. Stroke 2002; 33: 2722–7PubMedCrossRefGoogle Scholar
  33. 33.
    Adams HP. Emergent use of anticoagulation for treatment of patients with acute ischemic stroke. Stroke 2002; 33: 856–61PubMedCrossRefGoogle Scholar
  34. 34.
    International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischemic stroke. Lancet 1997; 349: 1569–81CrossRefGoogle Scholar
  35. 35.
    Caplan LR. Resolved: heparin may be useful in selected patients with brain ischemia. Stroke 2003; 34: 230–1PubMedCrossRefGoogle Scholar
  36. 36.
    Sandercock P. Full heparin anticoagulation should not be used in acute ischemic stroke. Stroke 2003; 34: 231–2PubMedCrossRefGoogle Scholar
  37. 37.
    Major ongoing stroke trials: rapid anticoagulation preventing ischemic damage (RAPID). Stroke 2003; 34(2): e1–e12Google Scholar
  38. 38.
    Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke: EAFT (European Atrial Fibrillation Trial) Study Group. Lancet 1993; 342(8882): 1255–62PubMedGoogle Scholar
  39. 39.
    Hart RG, Sherman DG, Easton JD, et al. Prevention of stroke in patients with nonvalvular atrial fibrillation. Neurology 1998; 51: 674–81PubMedCrossRefGoogle Scholar
  40. 40.
    Practice Parameter: stroke prevention in patients with nonvalvular atrial fibrillation. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1998; 51: 671–3CrossRefGoogle Scholar
  41. 41.
    Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336(4): 251–7PubMedCrossRefGoogle Scholar
  42. 42.
    Di Tullio M, Sacco RL, Gropal A, et al. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992; 117(6): 461–5PubMedGoogle Scholar
  43. 43.
    Cabanes L, Mas JL, Cohen A, et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. Stroke 1993; 24: 1865–73PubMedCrossRefGoogle Scholar
  44. 44.
    Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or TIA: French Study on Patent Foramen Ovale and Atrial Septal Aneurysm. Am Heart J 1995; 130: 1083–8PubMedCrossRefGoogle Scholar
  45. 45.
    Mas JL, Arquizan C, Lamy C, Atrial Septal Aneurysm Study Group, et al. Recurrent cerebrovasular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001; 345(24): 1740–6PubMedCrossRefGoogle Scholar
  46. 46.
    Homma S, Sacco RL, Di Tullio MR, PFO in Cryptogenic Stroke Study (PICSS) Investigators, et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in cryptogenic stroke study. Circulation 2002; 105(22): 2625–31PubMedCrossRefGoogle Scholar
  47. 47.
    Martin F, Sánchez PL, Doherty E, et al. Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Circulation 2002; 106: 1121–6PubMedCrossRefGoogle Scholar
  48. 48.
    Devuyst G, Bogousslavsky J, Ruchat P, et al. Prognosis after stroke followed by surgical closure of patent foramen ovale: a prospective follow-up study with brain MRI and simultaneous transesophageal and transcranial Doppler. Neurology 1996; 47: 1162–6PubMedCrossRefGoogle Scholar
  49. 49.
    Homma S, Di Tullio MR, Sacco RL, et al. Surgical closure of patent foramen ovale in selected patients with cryptogenic stroke: a preliminary study. Stroke 1997; 28: 2376–81PubMedCrossRefGoogle Scholar
  50. 50.
    Major ongoing stroke trials: evaluation of the STARflex® Septal Closure System in patients with a stroke or transient ischemic attack due to presumed paradoxical embolism through a PFO (CLOSURE). Stroke 2004; 35(2): e46–e57Google Scholar
  51. 51.
    Ducrocq X, Lacour JC, Debouverie M, et al. Accidents vasculaires cérébraux ischémiques du sujet jeune: étude prospective de 296 patients agés de 16 à 45 ans. Rev Neurol (Paris) 1999; 155: 575–82Google Scholar
  52. 52.
    Lucas C, Moulin T, Deplanque D, et al. Stroke patterns of internal carotid artery dissection in 40 patients. Stroke 1998; 29: 2646–8PubMedCrossRefGoogle Scholar
  53. 53.
    Schievink WI. Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med 2001; 344: 898–906PubMedCrossRefGoogle Scholar
  54. 54.
    Bushnell CD, Goldstein LB. Diagnostic testing for coagulopathies in patients with ischemic stroke. Stroke 2000; 31: 3067–78PubMedCrossRefGoogle Scholar
  55. 55.
    The APASS Writing Committee. Antiphospholipid antibodies and subsequent thromboocclusive events in patients with ischemic stroke. JAMA 2004; 291(5): 576–84CrossRefGoogle Scholar
  56. 56.
    Hinchey JA, Furlan AJ, Barnett HJM. Cardiogenic brain embolism: incidence, varieties, and treatment. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM, editors. Stroke: pathophysiology, diagnosis, and management. New York: Churchill Livingstone, 1998: 1089–119Google Scholar
  57. 57.
    Fredriksson K, Norrving B, Stromblad LG. Emergency reversal of anticoagulation after intracerebral hemorrhage. Stroke 1992; 23: 972–7PubMedCrossRefGoogle Scholar
  58. 58.
    Hylek EM, Skates SJ, Sheehan MA, et al. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with non-rheumatic atrial fibrillation. N Engl J Med 1996; 335: 540–6PubMedCrossRefGoogle Scholar
  59. 59.
    A randomised trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin: the Stroke Prevention In Reversible Ischemia Trial (SPIRIT) Study Group. Ann Neurol 1997; 42(6): 857–65CrossRefGoogle Scholar
  60. 60.
    Gorter JW. Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT): European Atrial Fibrillation Trial (EAFT) study groups. Neurology 1999; 53(6): 1319–27PubMedCrossRefGoogle Scholar
  61. 61.
    Hart RG, Halperin JL. Atrial fibrillation and stroke: concepts and controversies. Stroke 2001; 32: 803–8PubMedCrossRefGoogle Scholar
  62. 62.
    Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897–902PubMedGoogle Scholar
  63. 63.
    Hart RG, Boop BS, Anderson DC. Oral anticoagulants and intracranial hemorrhage: facts and hypotheses. Stroke 1995; 26: 1471–7PubMedCrossRefGoogle Scholar
  64. 64.
    Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study: Stroke Prevention in Atrial Fibrillation Investigators. Lancet 1994; 343: 687–91Google Scholar
  65. 65.
    Rosand J, Hylek EM, O’Donnell HC, et al. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 2000; 55: 947–51PubMedCrossRefGoogle Scholar
  66. 66.
    Wang TJ, Massaro JM, Levy D, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community. JAMA 2003; 290: 1049–56PubMedCrossRefGoogle Scholar
  67. 67.
    Man-Song-Hing M, Laupacis A. Anticoagulation-related bleeding in older persons with atrial fibrillation: physicians’s fears often unfounded. Arch Int Med 2003; 163: 1580–6CrossRefGoogle Scholar
  68. 68.
    Smith EE, Rosand J, Knudsen KA, et al. Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke. Neurology 2002; 59: 193–7PubMedCrossRefGoogle Scholar
  69. 69.
    Roob G, Schmidt R, Kapeller P, et al. MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology 1999; 52: 991–5PubMedCrossRefGoogle Scholar
  70. 70.
    Roob G, Lechner A, Schmidt R, et al. Frequency and location of microbleeds in patients with primary intracerebral hemorrhage. Stroke 2000; 31: 2665–9PubMedCrossRefGoogle Scholar
  71. 71.
    Phan TG, Koh M, Wijdicks EFM. Safety of discontinuation of anticoagulation in patients with intracranial hemorrhage at high thromboembolic risk. Arch Neurol 2000; 57: 1710–3PubMedCrossRefGoogle Scholar
  72. 72.
    Bertram M, Bonsanto M, Hacke W, et al. Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation. J Neurol 2000; 247: 209–14PubMedCrossRefGoogle Scholar
  73. 73.
    Hacke W. The dilemma of reinstituting anticoagualtion for patients with cardioembolic sources and intracranial hemorrhages: how wide is the strait between Skylla and Karybdis? Arch Neurol 2000; 57: 1682–4PubMedCrossRefGoogle Scholar
  74. 74.
    Vinters HV, Gilbert JJ. Cerebral amyloid angiopathy: incidence and complications in the aging brain: II. the distribution of amyloid vascular changes. Stroke 1983; 14: 924–8PubMedCrossRefGoogle Scholar
  75. 75.
    Kase CS. Cerebral amyloid angiopathy. In: Kase CS, Caplan LR, editors. Intracerebral Hemorrhage. Boston: Butterworth-Heinemann, 1994: 179–200Google Scholar
  76. 76.
    Vinters HV. Cerebral amyloid angiopathy. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM, editors). Stroke: Pathophysiology, diagnosis, and management. New York: Churchill Livingstone, 1998: 945–62Google Scholar
  77. 77.
    Fazekas F, Kleinert R, Roob G, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol 1999; 20: 637–42PubMedGoogle Scholar
  78. 78.
    Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324(7329): 71–86CrossRefGoogle Scholar
  79. 79.
    Hankey GJ, Warlow CP. Treatment and secondary prevention of stroke: evidence, costs, and effects on individuals and populations. Lancet 1999; 354: 1457–63PubMedCrossRefGoogle Scholar
  80. 80.
    Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study 2: dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143: 1–13PubMedCrossRefGoogle Scholar
  81. 81.
    Quinn MJ, Fitzgerald DJ. Ticlopidine and clopidogrel. Circulation 1999; 100: 1667–72PubMedCrossRefGoogle Scholar
  82. 82.
    A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE): CAPRIE Steering Committee. Lancet 1996; 348(9038): 1329–39CrossRefGoogle Scholar
  83. 83.
    Gent M, Blakely JA, Easton JD, et al. The Canadian American Ticlopidine Study (CATS) in thrombembolic stroke. Lancet 1989; 1(8649): 1215–20PubMedCrossRefGoogle Scholar
  84. 84.
    Hass WK, Easton JD, Adams HP Jr, et al. for the Ticlopidine Aspirin Stroke Study Group. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med 1989; 321: 501–7Google Scholar
  85. 85.
    MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70–99%) or with mild (0–29%) carotid stenosis. European Carotid Surgery Trialists’ Collaborative Group. Lancet 1991; 337(8752): 1235–43PubMedCrossRefGoogle Scholar
  86. 86.
    Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis: North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991; 325(7): 445–53CrossRefGoogle Scholar
  87. 87.
    Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998; 351(9113): 1379–87CrossRefGoogle Scholar
  88. 88.
    Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis: North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1998; 339: 1415–25PubMedCrossRefGoogle Scholar
  89. 89.
    Barnett HJ, Meldrum HE, Eliasziw M. The appropriate use of carotid endarterctomy. CMAJ 2002; 166: 1169–79PubMedGoogle Scholar
  90. 90.
    Sacco RL. Extracranial carotid stenosis. N Engl J Med 2001; 345: 1113–8PubMedCrossRefGoogle Scholar
  91. 91.
    Algra A, van Gijn J. Cumulative meta-analysis of aspirin efficacy after cerebral ischemia of arterial origin [letter]. J Neurol Neurosurg Psychiatry 1999; 66: 55Google Scholar
  92. 92.
    Hankey GJ, Sudlow CLM, Dunbabin DW. Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease?: a systematic review of the evidence from randomized trials. Stroke 2000; 31(7): 1779–84PubMedCrossRefGoogle Scholar
  93. 93.
    Rampal P, Moore N, van Ganse E, et al. Gastrointestinal tolerability of ibuprofen, compared with paracetamol and aspirin at over-the-counter doses. J Int Med Res 2002; 30: 301–8PubMedGoogle Scholar
  94. 94.
    A comparison of two doses of aspirin (30mg v 283mg a day) in patients after a transient ischemic attack or minor ischemic stroke: Dutch TIA Trial Study Group. N Engl J Med 1991; 325(18): 1261–6CrossRefGoogle Scholar
  95. 95.
    Sudlow C, Baigent C. Antiplatelet treatment (secondary prevention of stroke and secondary prevention of ischaemic cardiac events). In: Godlee F, Goldman D, editors. Clinical evidence (Issue 3). London, UK: BMJ Publishing Group and the American College of Physicians, American Society of Internal Medicine, 2000: 57–81Google Scholar
  96. 96.
    Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long-term use of aspirin: meta-analysis. BMJ 2000; 321: 1183–7PubMedCrossRefGoogle Scholar
  97. 97.
    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. Antiplatelet Trialists’ Collaboration. BMJ 1994; 308(6921): 81–106Google Scholar
  98. 98.
    Hart RG, Halperin JL, McBride R, et al. Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses. Arch Neurol 2000; 57: 326–32PubMedCrossRefGoogle Scholar
  99. 99.
    Pearson TA, Blair SN, Daniels SR, et al. AHA guidelines for primary prevention of cardiovascular disease and stroke: 2002 update. Circulation 2002; 106: 388–91PubMedCrossRefGoogle Scholar
  100. 100.
    Warlow C. Aspirin should be first-line antiplatelet therapy in the secondary prevention of stroke. Stroke 2002; 33: 2137–8PubMedCrossRefGoogle Scholar
  101. 101.
    Cleland JGF. Preventing atherosclerotic events with aspirin. BMJ 2002; 324: 103–5PubMedCrossRefGoogle Scholar
  102. 102.
    Major ongoing stroke trials: management of atherothrombosis with clopidogrel in high-risk patients with recent transient ischemic attack or ischemic stroke (MATCH). Stroke 2002; 33: 1733–4Google Scholar
  103. 103.
    Wilterdink JL, Easton JD. Dipyridamole plus aspirin in cerebrovascular disease. Arch Neurol 1999; 56: 1087–92PubMedCrossRefGoogle Scholar
  104. 104.
    Enserink M. Fraud and ethic charges hit stroke drug trial. Science 1996; 274: 2004–5PubMedCrossRefGoogle Scholar
  105. 105.
    Diener HC, Darius H, Bertrand-Hardy JM, et al. Does early high dosage dipyridamole in prevention of secondary stroke induce cardiac events? Z Kardiol 2001; 90: 348–51PubMedCrossRefGoogle Scholar
  106. 106.
    Hanssen CL, Williams E. Severe transmural myocardial ischemia after dipyridamole administration implicating coronary steal. Clin Cardiol 1998; 21: 293–6CrossRefGoogle Scholar
  107. 107.
    Pfisterer M. Intravenous dipyridamole for stress thallium-201 myocardial perfusion scintigraphy. Cardiovasc Imag 1992; 4: 31–9Google Scholar
  108. 108.
    Diener HC. Aspirin therapy should be first-line treatment in secondary prevention of stroke: against. Stroke 2002; 33: 2138–9PubMedCrossRefGoogle Scholar
  109. 109.
    Donnan GA, Davis SM. Aspirin therapy should be first line: probably, but watch this space. Stroke 2002; 33: 2139–40PubMedCrossRefGoogle Scholar
  110. 110.
    Major ongoing stroke trials: anticoagulants versus aspirin and the combination of aspirin and dipyridamole versus aspirin only in patients with transient ischemic attack or nondisabling ischemic stroke: ESPRIT (European/Australian Stroke Prevention in Reversible Ischemia Trial). Stroke 2002; 33(6): 1728Google Scholar
  111. 111.
    Algra A, de Schryver EL, van Gijn J, et al. Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2001: CD001342Google Scholar
  112. 112.
    Mohr JP, Thompson JL, Lazar RM, Warfarin-Aspirin Recurrent Stroke Study Group, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001; 345: 1444–51PubMedCrossRefGoogle Scholar
  113. 113.
    Goldstein LB, Adams R, Becker K, et al. Primary prevention of ischemic stroke: a statement for healthcare professionals from the stroke council of the American Heart Association. Circulation 2001; 103: 163–82PubMedCrossRefGoogle Scholar
  114. 114.
    Sacco RL, Benjamin EJ, Broderick JP, et al. AHA Conference Proceedings: risk factors. Stroke 1997; 28: 1507–17PubMedCrossRefGoogle Scholar
  115. 115.
    Gueyffier F, Boissel JP, Boutitie F, et al. Effect of antihypertensive treatment in patients having already suffered from stroke: gathering the evidence. The INDIANA (Individual Data Analysis of Antihypertensive intervention trials) Project Collaborators. Stroke 1997; 28(12): 2557–62Google Scholar
  116. 116.
    Gueyffier F, Bulpitt C, Boissel JP, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDIANA Group. Lancet 1999; 353(9155): 793–6Google Scholar
  117. 117.
    Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet 2000; 355: 865–72PubMedCrossRefGoogle Scholar
  118. 118.
    Perry Jr HM, Davis BR, Price TR, et al. Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: The Systolic Hypertension in the Elderly Program (SHEP). JAMA 2000; 284(4): 465–71PubMedCrossRefGoogle Scholar
  119. 119.
    Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342(3): 145–53PubMedCrossRefGoogle Scholar
  120. 120.
    Staessen JA, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 2001; 358: 1305–15PubMedCrossRefGoogle Scholar
  121. 121.
    PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–41CrossRefGoogle Scholar
  122. 122.
    Vasan RS, Larson RG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001; 345: 1291–7PubMedCrossRefGoogle Scholar
  123. 123.
    Hansson 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. HOT Study Group. Lancet 1998; 351(9118): 1755–62Google Scholar
  124. 124.
    Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham Study. JAMA 1979; 241: 2035–8PubMedCrossRefGoogle Scholar
  125. 125.
    Burchfiel CM, Curb JD, Rodriguez BL, et al. Glucose intolerance and 22-year stroke incidence: the Honolulu Heart Program. Stroke 1994; 25: 951–7PubMedCrossRefGoogle Scholar
  126. 126.
    Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34): UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352(9131): 854–65CrossRefGoogle Scholar
  127. 127.
    Effects of ramipril on cardiovascular and micro vascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000; 355(9200): 253–9CrossRefGoogle Scholar
  128. 128.
    Amarenco P. Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction. Neurology 2001; 57Suppl. 2: S35–44PubMedCrossRefGoogle Scholar
  129. 129.
    Blauw GJ, Lagaay AM, Smelt AHM, et al. Stroke, statins, and cholesterol: a meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. Stroke 1997; 28: 946–50PubMedCrossRefGoogle Scholar
  130. 130.
    Plehn JF, Davis BR, Sacks FM, et al. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The CARE Investigators. Circulation 1999; 99(2): 216–23Google Scholar
  131. 131.
    White HD, Simes RJ, Anderson NE, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000; 343: 317–26PubMedCrossRefGoogle Scholar
  132. 132.
    Sever PS, Dahlof B, Poulter NR, et al. for the ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial — Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149–58Google Scholar
  133. 133.
    Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360(9326): 7–22CrossRefGoogle Scholar
  134. 134.
    Major ongoing stroke trials: stroke prevention by aggressive reduction in cholesterol levels (SPARCL). Stroke 2004; 35(2): e46–57Google Scholar
  135. 135.
    Sacks F, Pfeffer M, Moye L, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335(14): 1001–9PubMedCrossRefGoogle Scholar
  136. 136.
    Pasternak RC, Smith SC, Bairey-Merz N, et al. ACC/AHA/ NHLBI clinical advisory on the use and safety of statins. Circulation 2002; 106: 1024–8PubMedCrossRefGoogle Scholar
  137. 137.
    Sappok T, Faulstich A, Stuckert E, et al. Compliance with secondary prevention of ischemic stroke: a prospective evaluation. Stroke 2001; 32: 1884–9PubMedCrossRefGoogle Scholar
  138. 138.
    Sudlow M, Rodgers H, Kenny RA, et al. Population based study of use of anticoagulants among patients with atrial fibrillation in the community. BMJ 1997; 314: 1529–30PubMedCrossRefGoogle Scholar
  139. 139.
    Albers GW, Bittar N, Young L, et al. Clinical characteristics and management of acute stroke in patients with atrial fibrillation admitted to US university hospitals. Neurology 1997; 48: 1598–604PubMedCrossRefGoogle Scholar
  140. 140.
    Gurwitz JH, Monette J, Rochon PA, et al. Atrial fibrillation and stroke prevention with warfarin in the long-term care setting. Arch Intern Med 1997; 157: 978–84PubMedCrossRefGoogle Scholar
  141. 141.
    Cohen N, Almoznino-Sarafian D, Alon I, et al. Warfarin for stroke prevention still underused in atrial fibrillation: patterns of omission. Stroke 2000; 31: 1217–22PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of NeurologyBerlinGermany

Personalised recommendations