Abstract
Cardiovascular disease is prevalent among patients with stroke; thus, cardiologists frequently treat patients at high risk for stroke. Results from recent clinical trials of antiplatelet medications, given alone or in combination, may be of special interest to cardiologists. The MATCH study demonstrated no significant difference between clopidogrel alone and clopidogrel plus aspirin in reducing risk of vascular events after stroke or transient ischemic attack. A 1.3% increased risk of major bleeding was associated with clopidogrel plus aspirin. In CHARISMA, clopidogrel plus aspirin did not reach statistical significance vs. placebo plus aspirin in reducing incidence of myocardial infarction (MI), stroke, or death from cardiovascular causes in patients with stable atherothrombotic disease; clopidogrel was associated with an increase in moderate bleeding. These results suggest that clopidogrel plus aspirin may be inappropriate as first‐line therapy for secondary stroke prevention. In patients with established cardiovascular disease at risk for MI or other vascular events, physicians must weigh the benefits and risks before choosing this therapy. Selection of an antiplatelet agent must be based on patient history, including previous MI and stroke, susceptibility to bleeding, and other high‐risk factors (e.g. advanced age and diabetes). Aspirin plus extended‐release dipyridamole may be more effective than clopidogrel for preventing stroke in high‐risk patients. This article strives to put MATCH and CHARISMA results into context by providing an overview of antiplatelet therapy, including relevant clinical trial results, a review of current practice guidelines, and a summary of an ongoing study that will improve clinical decision making. Copyright © 2007 Wiley Periodicals, Inc.
Keywords: antiplatelet therapy, secondary stroke prevention, stroke, transient ischemic attack
Full Text
The Full Text of this article is available as a PDF (271.6 KB).
References
- 1. Gorelick PB: Epidemiology of transient ischemic attack and ischemic stroke in patients with underlying cardiac disease. Clin Cardiol 2004; 27(issue 5, suppl 2): 4–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Vickrey BG, Rector TS, Wickstrom SL, et al.: Occurrence of secondary ischemic events among persons with atherosclerotic vascular disease. Stroke 2002; 33: 901–906. [DOI] [PubMed] [Google Scholar]
- 3. Elkind MSV: Secondary stroke prevention: review of clinical trials. Clin Cardiol 2004; 27(suppl 2): S25–S35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Rosamond W, Flegal K, Friday G, et al.: Heart Disease and Stroke Statistics–2007 Update. A report from The American Heart Association Statistics Committee and the Stroke Statistics Subcommittee. Circulation 2007; 115: e69–e171. [DOI] [PubMed] [Google Scholar]
- 5. Diener HC, Bogousslavsky J, Brass LM, et al.: 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. [DOI] [PubMed] [Google Scholar]
- 6. Bhatt DL, Fox KAA, Hacke W, et al.: Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. New Engl J Med 2006; 354: 1706–1717. [DOI] [PubMed] [Google Scholar]
- 7. 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. [PubMed] [Google Scholar]
- 8. Dutch TIA Trial Study Group : A comparison of two doses of aspirin (30 vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. New Engl J Med 1991; 325: 1261–1266. [DOI] [PubMed] [Google Scholar]
- 9. UK‐TIA Study Group : The United Kingdom Transient Ischaemic Attack (UK TIA) aspirin trial: final results. J Neurol Neurosur Ps 1991; 54: 1044–1546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. 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. [DOI] [PubMed] [Google Scholar]
- 11. Mohr JP, Thompson JL, Lazar RM, et al.: A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. Warfarin‐Aspirin Recurrent Stroke Study. New Engl J Med 2001; 345: 1444–1451. [DOI] [PubMed] [Google Scholar]
- 12. 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: 1–13. [DOI] [PubMed] [Google Scholar]
- 13. ESPRIT Study Group : Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006; 20(367): 1665–1673. [DOI] [PubMed] [Google Scholar]
- 14. CAPRIE Steering Committee : A randomized, blinded trial of clopidogrel versus aspirin in patients at risk for ischemic events. Lancet 1996; 348: 1329–1339. [DOI] [PubMed] [Google Scholar]
- 15. Diener HC, Sacco R, Yusuf S; for the 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 clopidogel) and telmisartan versus placebo in patients with strokes: the prevention Regimen for Effectively Avoiding Second Strokes Trial (ProFESS). Cerebrovasc Dis 2007; 23: 368–380. [DOI] [PubMed] [Google Scholar]
- 16. Antiplatelet 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: 71–86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Fayad P, Singh SP: Antithrombotic therapy for secondary prevention of ischemic stroke In Prevention and Treatment of Ischemic Stroke: Blue Books of Practical Neurology (Eds. Kasner SE, Gorelick PB.). Philadelphia: Butterworth‐Heinemann; 2004. [Google Scholar]
- 18. 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: 326–332. [DOI] [PubMed] [Google Scholar]
- 19. US Food and Drug Administration : Internal Analgesic, Antipyretic and Antirheumatic Drug Products for Over‐the‐Counter Human Use; Final Rule for Professional Labeling of Aspirin, Buffered Aspirin, and Aspirin in Combination with Antacid Drug Products. 63 Federal Register 56802 (1998; published correction appears at 63 Federal Register 66015) (codified at 21 CFR §343),1999. [PubMed]
- 20. Albers GW, Hart RG, Lutsep HL: Supplement to the guidelines for the management of transient ischemic attacks: a statement from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council, American Heart Association. Stroke 1999; 30: 2502–2511. [DOI] [PubMed] [Google Scholar]
- 21. Hass WK, Easton JD, Adams HP Jr.: A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high‐risk patients. New Engl J Med 1989; 321: 501–507. [DOI] [PubMed] [Google Scholar]
- 22.Ticlid (ticlopidine hydrochloride) [prescribing information]. Nutley, NJ: Roche Pharmaceuticals; 2001. [Google Scholar]
- 23. Albers GW, Amarenco P, Easton JD, et al.: Antithrombotic and thrombolytic therapy for ischemic stroke: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126: 483S–512S. [DOI] [PubMed] [Google Scholar]
- 24. Yusuf S, Zhao F, Mehta Sr, et al.: Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST‐segment elevation. New Engl J Med 2001; 345: 494–502. [DOI] [PubMed] [Google Scholar]