The American Journal of Medicine
Volume 122, Issue 4, Supplement 2 , Pages S21-S31 , April 2009

Recent Clinical Trials of Antiplatelet Therapy in Secondary Stroke Prevention: Expectations and Results for Application in Primary Care Settings

  • Helmi L. Lutsep, MD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to Helmi L. Lutsep, MD, Department of Neurology, Oregon Stroke Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, CR 131, Portland, Oregon 97239

References 

  1. Kikano GE, Brown MT. Antiplatelet therapy for atherothrombotic disease: an update for the primary care physician. Mayo Clin Proc. 2007;82:583–593
  2. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(suppl):483S–512S
  3. Sacco RL, Adams R, Albers G, et al. American Heart Association/American Stroke Association, the Council on Cardiovascular Radiology and Intervention, and the American Academy of Neurology Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke, co-sponsored by the Council on Cardiovascular Radiology and Intervention (The American Academy of Neurology affirms the value of this guideline). Circulation. 2006;113:e409–e449
  4. Johnston SC, Nguyen-Huynh MN, Schwarz ME, et al. National Stroke Association guidelines for the management of transient ischemic attacks. Ann Neurol. 2006;60:301–313
  5. Elkind MS. Implications of stroke prevention trials: treatment of global risk. Neurology. 2005;65:17–21
  6. Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med. 1998;339:1415–1425
  7. ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007;6:115–124
  8. Mohr JP, Thompson JL, Lazar RM, et al. Warfarin-Aspirin Recurrent Stroke Study Group A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345:1444–1451
  9. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86
  10. Miner J, Hoffhines A. The discovery of aspirin's antithrombotic effects. Tex Heart Inst J. 2007;34:179–186
  11. Pettigrew LC. Antithrombotic drugs for secondary stroke prophylaxis. Pharmacotherapy. 2001;21:452–463
  12. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest. 2001;119(suppl):300S–320S
  13. Eisert WG. Dipyridamole. In:  Michelson AD editors. Platelets. 2nd ed.. Oxford, England: Elsevier Science & Technology; 2006;p. 1165–1180
  14. Muller 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
  15. Bhatt DL, Fox KA, Hacke W, et al. CHARISMA Investigators Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706–1717
  16. Nappi J, Talbert R. Dual antiplatelet therapy for prevention of recurrent ischemic events. Am J Health Syst Pharm. 2002;59:1723–1735
  17. Algra A, van Gijn J. Aspirin at any dose above 30 mg offers only modest protection after cerebral ischaemia. J Neurol Neurosurg Psychiatry. 1996;60:197–199
  18. Johnson ES, Lanes SF, Wentworth CE, Satterfield MH, Abebe BL, Dicker LW. A metaregression analysis of the dose-response effect of aspirin on stroke. Arch Intern Med. 1999;159:1248–1253
  19. Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA. 2007;297:2018–2024
  20. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329–1339
  21. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study 2: dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1–13
  22. European Stroke Prevention Study 2 (Efficacy and safety data). J Neurol Sci. 1997;151(suppl):S1–S77
  23. De Schryver EL European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. Design of ESPRIT: an international randomized trial for secondary prevention after non-disabling cerebral ischaemia of arterial origin. Cerebrovasc Dis. 2000;10:147–150
  24. ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006;367:1665–1673
  25. Diener HC, Bogousslavsky J, Brass LM, et al. MATCH Investigators Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high risk patients (MATCH): randomised, double-blind, placebo controlled trial. Lancet. 2004;364:331–337
  26. Connolly S, Pogue J, Hart R, et al. ACTIVE Writing Group on behalf of the ACTIVE Investigators Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367:1903–1912
  27. Bhatt DL, Flather MD, Hacke W, et al. CHARISMA Investigators Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49:1982–1988
  28. Albers GW. Choice of endpoints in antiplatelet trials: which outcomes are most relevant to stroke patients?. Neurology. 2000;54:1022–1028
  29. Sacco RL, Sivenius J, Diener HC. Efficacy of aspirin plus extended-release dipyridamole in preventing recurrent stroke in high-risk populations. Arch Neurol. 2005;62:403–408
  30. Liao JK. Secondary prevention of stroke and transient ischemic attack: is more platelet inhibition the answer?. Circulation. 2007;115:1615–1621
  31. Diener HC, Sacco R, Yusuf S Steering Committee and PRoFESS Study Group. Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS). Cerebrovasc Dis. 2007;23:368–380
  32. Sacco RL, Diener HC, Yusuf S, et al. PRoFESS Study Group Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med. 2008;359:1238–1251
  33. Secondary Prevention of Small Subcortical Strokes (SPS3) Trial. [ClinicalTrials.gov Website.] March 2007 http://clinicaltrials.gov/ct/show/NCT00059306?order=1Accessed January 24, 2008. ClinicalTrials.gov Identifier NCT00059306
  34. SPS3: Secondary Prevention of Small Subcortical Strokes (SPOTRIAS) (Stroke Trials Registry). [The Internet Stroke Center at Washington University Website.] http://www.strokecenter.org/trials/TrialDetail.aspx?tid=79Accessed January 24, 2008. ISRCTN Identifier NCT00059306
  35. Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352:1305–1316

 Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

PII: S0002-9343(09)00141-7

doi: 10.1016/j.amjmed.2009.02.007

The American Journal of Medicine
Volume 122, Issue 4, Supplement 2 , Pages S21-S31 , April 2009