Skip to main content
SpringerLink
Log in

Antithrombotic secondary prevention after stroke

  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in terms of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow-release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some end points, it is superior to aspirin. Due to its side-effect profile (neutropenia, thrombotic thrombocytopenic purpura [TTP]), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 cannot be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Dennis M, Bamford J, Sandercock P, et al.: The prognosis of transient ischemic attacks in the community: the Oxfordshire Community Stroke project. Stroke 1991, 21:848–853.

    Google Scholar 

  2. Hankey GJ, Warlow CP, Slattery J: The prognosis of transient ischemic attacks. J Neurol 1990, 237:142.

    Google Scholar 

  3. Wilterdink JL, Easton JD: Vascular event rates in patients with atherosclerotic cerebrovascular disease. Arch Neurol 1992, 49:857–863.

    PubMed  CAS  Google Scholar 

  4. The Amaurosis Fugax Study Group: Current management of amaurosis fugax. Stroke 1990, 21:201–208.

    Google Scholar 

  5. Gueyffier R, Boissel JP, Boutitie F, et al.: Effect of antihypertensive treatment in patients having already suffered from stroke: gathering the evidence. Stroke 1997, 28:2557–2562.

    PubMed  CAS  Google Scholar 

  6. Randomised trial of a perindopril-based bloodpressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Progress Collaborative Group [no authors listed]. Lancet 2001,358:1033–1041.

  7. The Scandinavian Simvastatin Survival Study Group: Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994, 344:1383–1389.

    Google Scholar 

  8. Blauw GJ, Lagaay AM, Smelt AHM, et al.: Stroke, statins, and cholesterol: a meta-analysis of randomized, placebo-controlled, double-blind trials with HMGCoA reductase inhibitors. Stroke 1997, 28:946–950.

    PubMed  CAS  Google Scholar 

  9. Plehn JF, Davis BR, Sacks FM, et al.: Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. Circulation 1999, 99:216–223.

    PubMed  CAS  Google Scholar 

  10. Rosendorff C: Statins for prevention of stroke. Lancet 1998, 351:1002–1003.

    Article  PubMed  CAS  Google Scholar 

  11. The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Group: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998, 339:1349–1357.

    Article  Google Scholar 

  12. White HD, Simes RJ, Anderson NE, et al.: Pravastatin therapy and the risk of stroke. N Engl J Med 2000, 343:317–326.

    Article  PubMed  CAS  Google Scholar 

  13. Shepherd J, Blauw GJ, Murphy MB, et al.: The design of a prospective study of pravastatin in the elderly at risk (PROSPER). Am J Cardiol 1999, 84:1192–1197.

    Article  PubMed  CAS  Google Scholar 

  14. Rubins HB, Robins SJ, Collins D, et al.: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999, 341:410–418.

    Article  PubMed  CAS  Google Scholar 

  15. Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993, 329:977–986.

    Article  Google Scholar 

  16. Antiplatelet Trialists Collaboration: Secondary prevention of vascular disease by prolonged antiplatelet treatment. BMJ 1988, 296:320–331.

    Google Scholar 

  17. Patrono C, Roth GJ: Aspirin in ischemic cerebro-vascular disease. Stroke 1996, 27:756–760.

    PubMed  CAS  Google Scholar 

  18. American-Canadian Co-operative Study Group: Persantin-aspirin in cerebral ischemia, part II: endpoint results. Stroke 1985, 16:406–415.

    Google Scholar 

  19. Antiplatelet Trialists Collaboration: 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. BMJ 1994, 308:81–106.

    Google Scholar 

  20. Hart RG, Halperin JL: Atrial fibrillation and stroke: revisiting the dilemmas. Stroke 1994, 25:1337–1341.

    PubMed  CAS  Google Scholar 

  21. North American Symptomatic Carotid Endarterectomy Trial Collaborators: Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991, 325:445–453.

    Article  Google Scholar 

  22. European Carotid Surgery Trialists Collaborative Group: Randomized trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998, 351:1379–1387.

    Article  Google Scholar 

  23. The ESPS Group: The European Stroke Prevention Study (ESPS). Principal end-points. Lancet 1987, 2:1351–1354.

    Google Scholar 

  24. Diener HC, Forbes C, Riekkinen PJ, et al.: European Stroke Prevention Study 2: efficacy and safety data. J Neurol Sci 1997, 151:S1-S77.

    Article  Google Scholar 

  25. Gent M, Blakely JA, Easton JD, et al.: The Canadian American ticlopidine study (CATS) in thromboembolic stroke. Lancet 1989, 1:1215–1220.

    Article  PubMed  CAS  Google Scholar 

  26. International Stroke Trial Collaborative Group: The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischemic stroke. Lancet 1997, 349:1564–1565.

    Article  Google Scholar 

  27. CAST (Chinese Acute Stroke Trial) Collaborative Group: CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischemic stroke. Lancet 1997, 349:1641–1649.

    Article  Google Scholar 

  28. UK-TIA Study Group: The United Kingdom transient ischemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991, 54:1044–1054.

    Article  Google Scholar 

  29. The SALT Collaborative Group: Swedish aspirin low-dose trial (SALT) of 75-mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. Lancet 1991, 338:1345–1349.

    Article  Google Scholar 

  30. ESPS-Working Group: Second European stroke prevention study. J Neurol 1992, 239:299–301.

    Article  Google Scholar 

  31. Diener HC, Cuhna L, Forbes C, et al.: European Stroke Prevention Study 2: dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996, 143:1–13.

    Article  PubMed  CAS  Google Scholar 

  32. Hass WK, Easton JD, Adams HP, et al.: A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke. N Engl J Med 1989, 321:501–507.

    Article  PubMed  CAS  Google Scholar 

  33. CAPRIE Steering Committee: A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet 1996, 348:1329–1339.

    Article  Google Scholar 

  34. Dyken ML, Barnett HJM, Easton JD, et al.: Low-dose aspirin and stroke: “ It ain’t necessarily so”. Stroke 1992, 23:1395–1399.

    PubMed  CAS  Google Scholar 

  35. Dyken ML: Controversies in stroke: past and present. The Willis lecture. Stroke 1993, 24:1251–1258.

    PubMed  CAS  Google Scholar 

  36. Diener HC: Use of acetylsalicylic acid in the secondary prevention of stroke. Int J Clin Pract 1998, Suppl 97:12–15.

    Google Scholar 

  37. Algra A, van GijnJ: Aspirin at any dose above 30 mg offers only modest protection after cerebral ischemia. J Neurol Neurosurg Psychiatry 1996, 60:197–199.

    PubMed  CAS  Google Scholar 

  38. Algra A, van Gijn J: Cumulative meta-analysis of aspirin efficacy after cerebral ischemia of arterial origin. J Neurol Neurosurg Psychiatry 1999, 65:255. A good review.

    Google Scholar 

  39. Department of Health and Human Services, US Food and Drug Administration: Internal analgesic, antipyretic, and anti-rheumatic drug products for overthe counter human use. Final rule for professional labeling of aspirin, buffered aspirin, and aspirin in combination with antacid drug products. Federal Register 1998, 63:56802–56819.

    Google Scholar 

  40. The Dutch TIA Trial Study Group: A comparison of two doses of aspirin (30 mg vs 283 mg/day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med 1991, 325:1261–1266.

    Article  Google Scholar 

  41. Page Y, Tardy B, Zeni F, et al.: Thrombotic thrombocytopenic purpura related to ticlopidine. Lancet 1991, 337:774–776.

    Article  PubMed  CAS  Google Scholar 

  42. Bennett CL, Kiss JE, Weinberg PD, et al.: Thrombotic thrombocytopenic purpura after stenting and ticlopidine. Lancet 1998, 352:1036–1037.

    Article  PubMed  CAS  Google Scholar 

  43. Bennett CL, Connors JM, Carwile JM, et al.: Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 2000, 342:1773–1777. An excellent article.

    Article  PubMed  CAS  Google Scholar 

  44. Patrono C, Coller B, Dalen JE, et al.: Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest 1998, 114(suppl):470S-488S.

    PubMed  CAS  Google Scholar 

  45. Guiraud-Chaumeil B, Rascol A, David J, et al.: Prevention des recidives des accidents vasculaires cerebraux ischemiques par les anti-agregants plaquettaires. Rev Neurol (Paris) 1982, 138:367–385.

    CAS  Google Scholar 

  46. Bousser MG, Eschwege E, Haguenau M, et al.: " A.I.C.L.A." controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischemia. Stroke 1983, 13:5–14.

    Google Scholar 

  47. Müller TH, Su CA, Weisenberger H, et al.: Dipyridamole alone or combined with low dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo. Br J Clin Pharmacol 1990, 30:179–186.

    PubMed  Google Scholar 

  48. EAFT Group: Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993, 342:1255–1262.

    Google Scholar 

  49. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group: A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. Ann Neurol 1997, 42:857–865.

    Article  Google Scholar 

  50. Mohr JP, Thompson JL, Lazar RM, et al.: A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001, 345:1444–1451.

    Article  PubMed  CAS  Google Scholar 

  51. Chimowitz M, Kokkinos J, Strong J, et al.: The warfarin-aspirin symptomatic intracranial disease study. Neurology 1995, 45:1488–1493.

    PubMed  CAS  Google Scholar 

  52. Topol EJ, Byzova TV, Plow EF: Platelet GPIIb-IIIa blockers. Lancet 1999, 353:227–231.

    Article  PubMed  CAS  Google Scholar 

  53. Topol EJ, Eston JD, Amarenco P, et al.: Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trial. Am Heart J 2000, 139:927–933.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, University of Essen, Hufelandstrasse 55, 45122, Essen, Germany

    Hans-Christoph Diener MD, PhD & Peter Ringleb MD

Authors
  1. Hans-Christoph Diener MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Ringleb MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Diener, HC., Ringleb, P. Antithrombotic secondary prevention after stroke. Curr Treat Options Cardio Med 4, 429–440 (2002). https://doi.org/10.1007/s11936-002-0022-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11936-002-0022-4

Keywords

Search

Navigation