Clinical Drug Investigation

, Volume 24, Issue 5, pp 245–254 | Cite as

Risk Reduction Strategies in Ischaemic Stroke

The Role of Antiplatelet Therapy
Review Article

Abstract

Stroke is a common and serious disorder, and is a leading cause of disability and death in adults. Transient ischaemic attacks are now recognised as being common precursors of stroke, with a high risk of subsequent vascular events. The majority of strokes are ischaemic in origin, and are typically due to atherothrombosis/microatheromatosis involving a large or small cerebral blood vessel or to an embolic event. Owing to the diffuse nature of atherothrombosis, these patients are at risk of ischaemic events in other vascular beds. Options for treating patients with acute ischaemic stroke are very limited; therefore prevention is a key strategy for reducing the risk of recurrent stroke and other vascular events. Treatment of risk factors such as hypertension, diabetes mellitus, smoking and obesity is an important approach for stroke prevention. Platelets are involved in the development of thrombi and emboli, making antiplatelet therapy an important preventive strategy. Antiplatelet agents are effective in preventing recurrent ischaemic stroke and other vascular ischaemic events, such as myocardial infarction and vascular death. In some cases, anticoagulants may be effective in preventing ischaemic stroke recurrence. Carotid endarterectomy can reduce stroke risk in patients with moderate- or high-grade carotid artery stenosis. Choosing the most appropriate therapy for the individual patient is key to optimising stroke prevention.

Keywords

Aspirin Ischaemic Stroke Clopidogrel Antiplatelet Therapy Ticlopidine 

Notes

Acknowledgements

Dr Alberts is a consultant and has received honoraria and research funding from Sanofi, Bristol-Myers Squibb and Boehringer-Ingelheim.

References

  1. 1.
    Mohr JP, Albers GW, Amarenco P, et al. Etiology of stroke. Stroke 1997; 28: 1501–6PubMedCrossRefGoogle Scholar
  2. 2.
    Lammie GA. Hypertensive cerebral small vessel disease and stroke. Brain Pathol 2002; 12: 358–70PubMedGoogle Scholar
  3. 3.
    De Jong G, Kessels F, Lodder J. Two types of lacunar infarcts: further arguments from a study on prognosis. Stroke 2002; 33: 2072–6PubMedCrossRefGoogle Scholar
  4. 4.
    Albers GW, Caplan LR, Easton JD, et al. Transient ischemic attack: proposal for a new definition. N Engl J Med 2002; 347: 1713–6PubMedCrossRefGoogle Scholar
  5. 5.
    Johnston SC, Gress DR, Browner WS, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000; 284: 2901–6PubMedCrossRefGoogle Scholar
  6. 6.
    Hankey GJ. Long-term outcome after ischaemic stroke/transient ischaemic attack. Cerebrovasc Dis 2003; 16 Suppl. 1: 14–9PubMedCrossRefGoogle Scholar
  7. 7.
    Droste DW, Ringelstein EB. Evaluation of progression and spread of atherothrombosis. Cerebrovasc Dis 2002; 13 Suppl. 1: 7–11PubMedCrossRefGoogle Scholar
  8. 8.
    Sacco RL, Shi T, Zamanillo MC, et al. Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: the Northern Manhattan Stroke Study. Neurology 1994; 44: 626–34PubMedCrossRefGoogle Scholar
  9. 9.
    Hardie K, Hankey GJ, Jamrozik K, et al. Ten-year survival after first-ever stroke in the Perth Community Stroke Study. Stroke 2003; 34: 1842–6PubMedCrossRefGoogle Scholar
  10. 10.
    Bauters C. Atherothrombosis: the same process for different arterial territories? Ann Cardiol Angeiol (Paris) 2002; 51: 177–80CrossRefGoogle Scholar
  11. 11.
    Yuan C, Zhang SX, Polissar NL, et al. Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke. Circulation 2002; 105: 181–5PubMedCrossRefGoogle Scholar
  12. 12.
    Carr S, Farb A, Pearce WH, et al. Atherosclerotic plaque rupture in symptomatic carotid artery stenosis. J Vasc Surg 1996; 23: 755–65PubMedCrossRefGoogle Scholar
  13. 13.
    Corti R, Badimon JJ. Biologic aspects of vulnerable plaque. Curr Opin Cardiol 2002; 17: 616–25PubMedCrossRefGoogle Scholar
  14. 14.
    Harker LA. Therapeutic inhibition of platelet function in stroke. Cerebrovasc Dis 1998; 8 Suppl. 5: 8–18PubMedCrossRefGoogle Scholar
  15. 15.
    Marquardt L, Ruf A, Mansmann U, et al. Course of platelet activation markers after ischemic stroke. Stroke 2002; 33: 2570–4PubMedCrossRefGoogle Scholar
  16. 16.
    DiNapoli M, Papa F, the Villa Pini Stroke Data Bank Investigators. Inflammation, hemostatic markers, and antithrombotic agents in relation to long-term risk of new cardiovascular events in first-ever ischemic stroke patients. Stroke 2002; 33: 1763–71PubMedCrossRefGoogle Scholar
  17. 17.
    Blann AD, Landray MJ, Lip GY. ABC of antithrombotic therapy: an overview of antithrombotic therapy. BMJ 2002; 325: 762–5PubMedCrossRefGoogle Scholar
  18. 18.
    UK-TIA Study Group. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991; 54: 1044–54CrossRefGoogle Scholar
  19. 19.
    Lai SM, Alter M, Friday G, et al. A multifactorial analysis of risk factors for recurrence of ischemic stroke. Stroke 1994; 25: 958–62PubMedCrossRefGoogle Scholar
  20. 20.
    Collins R, MacMahon S. Blood pressure, antihypertensive drug treatment and the risks of stroke and coronary artery disease. Br Med Bull 1994; 50: 272–98PubMedGoogle Scholar
  21. 21.
    Leys D, Deplanque D, Mounier-Vehier C, et al. Stroke prevention: management of modifiable vascular risk factors. J Neurol 2002; 249: 507–17PubMedCrossRefGoogle Scholar
  22. 22.
    Ginsberg HN. Treatment for patients with the metabolic syndrome. Am J Cardiol 2003; 91(7A): 29–39ECrossRefGoogle Scholar
  23. 23.
    Straus SE, Majumdar SR, McAlister FA. New evidence for stroke prevention: scientific review. JAMA 2002; 288: 1388–95PubMedCrossRefGoogle Scholar
  24. 24.
    Hart RG, Halperin JL, McBride R, et al. Aspirin for the primary prevention of stroke and other major vascular events. Arch Neurol 2000; 57: 326–32PubMedCrossRefGoogle Scholar
  25. 25.
    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: 129–35CrossRefGoogle Scholar
  26. 26.
    Eidelman RS, Hebert PR, Weisman SM, et al. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med 2003; 163: 2006–10PubMedCrossRefGoogle Scholar
  27. 27.
    Byington RP, Davis BR, Plehn JF, et al. Reduction of stroke event with pravastatin: the Prospective Pravastatin Pooling (PPP) project. Circulation 2001; 103: 387–92PubMedCrossRefGoogle Scholar
  28. 28.
    Waters DD, Schwartz GG, Olsson AG, et al. Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Circulation 2002; 106: 1690–5PubMedCrossRefGoogle Scholar
  29. 29.
    Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004: 363: 757–67CrossRefGoogle Scholar
  30. 30.
    Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-97Google Scholar
  31. 31.
    Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22CrossRefGoogle Scholar
  32. 32.
    Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2002; 342: 145–53Google Scholar
  33. 33.
    Sleight P, Yusuf S, Pogue J, et al. Blood pressure reduction and cardiovascular risk in HOPE study. Lancet 2001; 358: 2130–1PubMedCrossRefGoogle Scholar
  34. 34.
    Progress Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6, 105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–41CrossRefGoogle Scholar
  35. 35.
    Coull BM, Williams LS, Goldstein LB, et al. Anticoagulants and antiplatelet agents in acute ischemic stroke: report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association. Stroke 2002; 33: 1934–42PubMedCrossRefGoogle Scholar
  36. 36.
    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: 71–86CrossRefGoogle Scholar
  37. 37.
    Grundmann K, Jaschonek K, Kleine B, et al. Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 2003; 250: 63–6PubMedCrossRefGoogle Scholar
  38. 38.
    Gum PA, Kottke-Marchant K, Welsh PA, et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41: 961–5PubMedCrossRefGoogle Scholar
  39. 39.
    Alberts MJ, Bergman DL, Molner E, et al. Antiplatelet effect of aspirin in patients with cerebrovascular disease. Stroke 2004; 35: 175–8PubMedCrossRefGoogle Scholar
  40. 40.
    Valles J, Santos MT, Aznar J, et al. Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity. Circulation 1998; 97: 350–5PubMedCrossRefGoogle Scholar
  41. 41.
    Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclo-oxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001; 345: 1809–17PubMedCrossRefGoogle Scholar
  42. 42.
    MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet 2003; 361: 573–4PubMedCrossRefGoogle Scholar
  43. 43.
    Howes LG, Kram H. Selective cyclo-oxygenase-2 inhibitors and myocardial infarction: how strong is the link? Drag Saf 2002; 25: 829–35CrossRefGoogle Scholar
  44. 44.
    Hankey GJ, Sudlow CLM, Dunbabin PW. 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: 1779–84PubMedCrossRefGoogle Scholar
  45. 45.
    CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329–39CrossRefGoogle Scholar
  46. 46.
    Hacke W. From CURE to MATCH: ADP receptor antagonists as the treatment of choice for high-risk atherothrombotic patients. Cerebrovasc Dis 2002; 13 Suppl. 1: 22–6PubMedCrossRefGoogle Scholar
  47. 47.
    CURE Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502CrossRefGoogle Scholar
  48. 48.
    Steinhubl SR, Berger PB, Mann JT, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002; 288: 2411–20PubMedCrossRefGoogle Scholar
  49. 49.
    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
  50. 50.
    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: 501–7CrossRefGoogle Scholar
  51. 51.
    Gorelick PB, Richardson D, Kelly M, et al. Aspirin and ticlopidine for prevention of recurrent stroke in Black patients: a randomized trial. JAMA 2003; 289: 3005–7CrossRefGoogle Scholar
  52. 52.
    He J, Whelton PK, Vu B, et al. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA 1998; 280: 1930–5PubMedCrossRefGoogle Scholar
  53. 53.
    Serebraany VL, Malinin AI, Eisert RM, et al. Risk of bleeding complications with antiplatelet agents: meta-analysis of 338, 191 patients enrolled in 50 randomized controlled trials. Am J Hematol 2004; 75: 40–7CrossRefGoogle Scholar
  54. 54.
    Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000; 321: 1183–7PubMedCrossRefGoogle Scholar
  55. 55.
    Zakarija A, Bandarenko N, Pandey DK, et al. Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration. Stroke 2004: 35: 533–7PubMedCrossRefGoogle Scholar
  56. 56.
    Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001; 119(1 Suppl. ): 300S–20SPubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Room 1420, Department of NeurologyNorthwestern University Medical SchoolChicagoUSA
  2. 2.Sutter Medical CenterSacramentoUSA

Personalised recommendations