, Volume 42, Supplement 5, pp 39–50 | Cite as

Antiplatelet Therapy in the Prevention of Stroke

  • J. D. Easton
Section 2


Aspirin (acetylsalicylic acid) is effective in reducing vascular outcome events in patients with atherosclerosis: a relative risk reduction of about 30% for stroke, 22% for stroke and death, and 15% for vascular mortality. It is probable that low and high dose aspirin are similar in efficacy. Complications are more frequent with high dose aspirin than with low doses.

Four randomised trials evaluating sulfinpyrazone vs placebo, and 3 trials evaluating sulfinpyrazone vs aspirin, showed more cerebrovascular events in the sulfinpyrazone group than in the aspirin and placebo groups.

One small trial comparing dipyridamole with placebo in patients with cerebrovascular disease found no difference between the 2 groups in outcome. No other studies have compared dipyridamole alone with placebo or aspirin. The European Stroke Prevention Study II is currently in progress and is comparing dipyridamole + aspirin, dipyridamole, aspirin, and placebo.

In the first year, the Ticlopidine Aspirin Stroke Study (TASS) showed a 42% risk reduction for stroke and death using the efficacy analysis and a 47% risk reduction for stroke and stroke death. Ticlopidine was more effective than aspirin in reducing stroke in both males and females. Apart from a reversible severe neutropenia in 0.86% of patients, ticlopidine-related adverse effects were relatively benign and reversible. The Canadian-American Ticlopidine Study (CATS) compared ticlopidine with placebo in patients with completed major strokes. The cumulative event rates for the primary outcome events of stroke, myocardial infarction and vascular death, using the efficacy approach, show clear evidence of separation almost immediately after randomisation, consistent with a constant risk reduction of about 30% in the ticlopidine group. These data provide strong evidence that ticlopidine conveys a clinically important reduction in the risk of thromboembolic events in patients with a history of completed thromboembolic stroke.

In conclusion, aspirin is effective in preventing atherothrombotic morbidity and mortality. It reduces the overall vascular event rate by about 25%. Sulfinpyrazone and dipyridamole appear to add nothing important over aspirin alone. Ticlopidine is more effective than aspirin in preventing stroke. The modest, reversible risk of neutropenia, affecting less than 1% of patients, makes the benefit: risk ratio a reasonable one.


Aspirin Dipyridamole Ticlopidine Relative Risk Reduction Nonfatal Stroke 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acheson J, Danta G, Hutchinson EC. Controlled trial of dipyridamole in cerebral vascular disease. British Medical Journal 1: 614–615, 1969PubMedCrossRefGoogle Scholar
  2. American-Canadian Co-operative Study Group. Persantine aspirin trial in cerebral ischemia. Part II: Endpoint results. Stroke 16: 406–415, 1985CrossRefGoogle Scholar
  3. Antiplatelet Trialists’ Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet treatment. British Medical Journal 296: 320–331, 1988CrossRefGoogle Scholar
  4. Balsano F, Rizzon P, Violi F, Scrutinio D, Cimminiello C, et al. Studia della Ticlopidina nell’Angina Instabile Group. Antiplatelet treatment with ticlopidine in unstable angina: a controlled multicenter clinical trial. Circulation 82: 17–26, 1990PubMedCrossRefGoogle Scholar
  5. Barnett HJM. Proceedings of the International Conference on Stroke, Geneva, Switzerland, May 30–June 1, 1991. The World Federation of Neurology, 1991Google Scholar
  6. Blakely JA. A prospective trial of sulfinpyrazone and survival after thrombotic stroke. Thrombosis et Diathesis Haemorrhagica 42: 161, 1979Google Scholar
  7. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. New England Journal of Medicine 323: 1505–1511, 1990CrossRefGoogle Scholar
  8. Bousser MG, Eschwege E, Haguenau M, et al. ‘AICLA’ controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischemia. Stroke 14: 5–14, 1983PubMedCrossRefGoogle Scholar
  9. Byer JA, Easton JD. Therapy of ischemic cerebrovascular disease. Annals of Internal Medicine 93: 742–756, 1980PubMedGoogle Scholar
  10. Canadian Cooperative Study Group: a randomized trial of aspirin and sulfinpyrazone in threatened stroke. New England Journal of Medicine 299: 53–59, 1978CrossRefGoogle Scholar
  11. Chesebro JH, Fuster V, Pumphrey CW, et al. Combined warfarin-platelet inhibitor antithrombotic therapy in prosthetic heart valve replacement. Circulation 64(Suppl. IV): IV76, 1981Google Scholar
  12. Connolly SJ, et al. Results of the Canadian Atrial Fibrillation Study. Journal of the American College of Cardiology, in press, 1991Google Scholar
  13. Dutch TIA Trial Study Group. The Dutch TIA Trial: protective effects of low-dose aspirin and atenolol in patients with transient ischemic attacks or nondisabling stroke. Stroke 19: 512–517, 1988CrossRefGoogle Scholar
  14. Dutch TIA Trial 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. New England Journal of Medicine 325: 1261–1266, 1991CrossRefGoogle Scholar
  15. Easton JD, Hart RG, Kaste M, Sherman DG. Diagnosis and management of ischemic stroke. Part I. Threatened stroke and its management. Current Problems in Cardiology 8: 1–76, 1983CrossRefGoogle Scholar
  16. ESPS Group: the European stroke prevention study (ESPS). Principal end-points. Lancet 2: 1351–1354, 1987Google Scholar
  17. European Carotid Surgery Trialists’ Collaborative Group. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70–99%) or with mild (0–29%) carotid stenosis. Lancet 337: 1235–1243, 1991CrossRefGoogle Scholar
  18. Fields WS, Lemak NA, Frankowski RF, Hardy RJ. Controlled trial of aspirin in cerebral ischemia. Stroke 8: 301–316, 1977PubMedCrossRefGoogle Scholar
  19. Fields WS, Lemak NA, Frankowski RF, Hardy RJ. Controlled trial of aspirin in cerebral ischemia, part II. Stroke 9: 309–319, 1978PubMedCrossRefGoogle Scholar
  20. Gent M, Barnett HJ, Sackett DL, Taylor DW. A randomized trial of aspirin and sulfinpyrazone in patients with threatened stroke. Results and methodologic issues. Circulation 62(Suppl. V): V97–V105, 1980PubMedGoogle Scholar
  21. Gent M, Blakely JA, Easton JD, Ellis DJ, Hachinski VC, et al. The Canadian American ticlopidine study (CATS) in thromboembolic stroke: design, organization and baseline results. Stroke 19: 1203–1210, 1988PubMedCrossRefGoogle Scholar
  22. Gent M, Easton JD, Hachinski VC, Panak E, Sicurella J, et al. The Canadian-American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1: 1215–1220, 1989PubMedCrossRefGoogle Scholar
  23. Guiraud-Chaumeil B, Rascol A, David A, Boneu B, Clanet M, et al. Prevention des recidives des accidents vasculaires cerebraux ischemiques par les anti-aggregants plaquettaires; resultats d’un essai therapeutique controle de 3 ans. Revue Neurologique 138: 367–385, 1982PubMedGoogle Scholar
  24. Hass WK, Easton JD, Adams Jr HP, 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
  25. Janzon L, Bergqvist D, Boberg J, Boberg M, Eriksson I, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effect of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. Journal of Internal Medicine 227: 301–308, 1990PubMedCrossRefGoogle Scholar
  26. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. Lancet 1: 175–179, 1989PubMedCrossRefGoogle Scholar
  27. Peto R, Gray R, Collins R, Wheatley K, Hennekens C, et al. Randomized trial of prophylactic daily aspirin in British male doctors. British Medical Journal 1: 313–316, 1988CrossRefGoogle Scholar
  28. Robertson JT, Dugdale M, Salky N, Robinson H. The effect of a platelet inhibiting drug in the therapy of patients with transient ischaemic attacks and strokes. Thrombosis et Diathesis Haemorrhagica 34: 598, 1975PubMedGoogle Scholar
  29. Salt Collaborative Group. Swedish Aspirin Low-dose Trial (SALT) of 75mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. Lancet 2: 1345–1349, 1991CrossRefGoogle Scholar
  30. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. New England Journal of Medicine 323: 147–152, 1990PubMedCrossRefGoogle Scholar
  31. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing Physicians’ Health Study. New England Journal of Medicine 321: 129–135, 1989CrossRefGoogle Scholar
  32. Stroke Prevention in Atrial Fibrillation Study Group. Preliminary report of the Stroke Prevention in Atrial Fibrillation Study. New England Journal of Medicine 322: 863–868, 1990Google Scholar
  33. Swedish Cooperative Study. High-dose acetylsalicylic acid after cerebral infarction. Stroke 18: 325–334, 1987CrossRefGoogle Scholar
  34. Tohgi H. The effect of ticlopidine on TIA compared with aspirin: a double-blind, twelve-month follow-up study. Agents and Actions 15 (Suppl.): 279–282, 1984PubMedCrossRefGoogle Scholar
  35. UK-TIA Study Group. United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results. British Medical Journal 1: 316–320, 1988CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • J. D. Easton
    • 1
  1. 1.Department of NeurologyRhode Island Hospital-Brown UniversityProvidenceUSA

Personalised recommendations