Antiplatelet medications are an important part of the therapy of cerebrovascular diseases. Oral agents such as aspirin have an established role in the secondary prevention of stroke. An aspirin and dipyridamole combination has recently been approved. Ticlopidine has been proven to be more effective than aspirin, but its potentially serious side effect profile makes long-term use hazardous. Clopidogrel has been demonstrated to be both more effective than and at least as safe as aspirin. The combination of clopidogrel plus aspirin represents the likely future therapy for high-risk patients. The role of oral antiplatelet therapy in the acute treatment of stroke is beginning to be clarified. Aspirin treatment appears to be strongly indicated. Intravenous antiplatelet therapy with glycoprotein IIb/IIIa inhibitors for acute stroke and as an adjunct to carotid artery stenting appears promising.

1.
Website: AHA. American Heart Association Statistics. www.americanheart.org 2000.
2.
Bhatt DL, Topol EJ: Antiplatelet and anticoagulant therapy in the secondary prevention of ischemic heart disease. Med Clin North Am 2000;84:163–179.
3.
Topol EJ, Yadav JS: Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation 2000;101:570–580.
4.
Bhatt DL, Topol EJ: Embolization as a pathological mechanism; in Topol EJ (ed): Acute Coronary Syndromes, ed 2. New York, Dekker, in press.
5.
Golledge J, Greenhalgh RM, Davies AH: The symptomatic carotid plaque. Stroke 2000;31:774–781.
6.
Choudhri TF, Hoh BL, Zerwes HG, Prestigiacomo CJ, Kim SC, Connolly ES Jr, Kottirsch G, Pinsky DJ: Reduced microvascular thrombosis and improved outcome in acute murine stroke by inhibiting GP IIb/IIIa receptor-mediated platelet aggregation. J Clin Invest 1998;102:1301–1310.
7.
Dietrich WD, Danton G, Hopkins AC, Prado R: Thromboembolic events predispose the brain to widespread cerebral infarction after delayed transient global ischemia in rats. Stroke 1999;30:855–861.
8.
Huang J, Kim LJ, Mealey R, Marsh HC Jr, Zhang Y, Tenner AJ, Connolly ES Jr, Pinsky DJ: Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science 1999;285:595–599.
9.
Adunsky A, Hershkowitz M, Atar E, Bakoun M, Poreh A: Infarct volume, neurological severity and PAF binding to platelets of patients with acute cerebral ischemic stroke. Neurol Res 1999;21:645–648.
10.
Minamino T, Kitakaze M, Sanada S, Asanuama H, Kurotobi T, Koretsune Y, Fukunami M, Kuzuya T, Hoki N, Hori M: Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: Role of nitric oxide. Circulation 1998;98:1721–1727.
11.
Jordan WD Jr, Voellinger DC, Doblar DD, Plyushcheva NP, Fisher WS, McDowell HA: Microemboli detected by transcranial Doppler monitoring in patients during carotid angioplasty versus carotid endarterectomy. Cardiovasc Surg 1999;7:33–38.
12.
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.
13.
UK-TIA Study Group: United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial: Interim results. Br Med J (Clin Res Ed) 1988;296:316–320.
14.
Taylor DW, Barnett HJ, Haynes RB, Ferguson GG, Sackett DL, Thorpe KE, Simard D, Silver FL, Hachinski V, Clagett GP, Barnes R, Spence JD: Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: A randomized controlled trial. ASA and Carotid Endarterectomy (ACE) Trial Collaborators. Lancet 1999;353:2179–2184.
15.
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;321:129–135.
16.
He J, Whelton PK, Vu B, Klag MJ: Aspirin and risk of hemorrhagic stroke: A meta-analysis of randomized controlled trials. JAMA 1998;280:1930–1935.
17.
Hart RG, Halperin JL, McBride R, Benavente O, Man-Son-Hing M, Kronmal RA: Aspirin for the primary prevention of stroke and other major vascular events: Meta-analysis and hypotheses. Arch Neurol 2000;57:326–332.
18.
Hart RG, Pearce LA, Miller VT, Anderson DC, Rothrock JF, Albers GW, Nasco E: Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: Frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies. Cerebrovasc Dis 2000;10:39–43.
19.
Hart RG, Benavente O, McBride R, Pearce LA: Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: A meta-analysis. Ann Intern Med 1999;131:492–501.
20.
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.
21.
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;349:1569–1581.
22.
Easton JD: What have we learned from recent antiplatelet trials? Neurology 1998;51(suppl 3):36–38.
23.
Bednar MM, Gross CE: Antiplatelet therapy in acute cerebral ischemia. Stroke 1999;30:887–893.
24.
Helgason CM, Bolin KM, Hoff JA, Winkler SR, Mangat A, Tortorice KL, Brace LD: Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994;25:2331–2336.
25.
Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Löwenthal A: European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996;143:1–13.
26.
Tijssen JG: Low-dose and high-dose acetylsalicylic acid, with and without dipyridamole: A review of clinical trial results. Neurology 1998;51(suppl):15–16.
27.
Theis JG, Deichsel G, Marshall S: Rapid development of tolerance to dipyridamole-associated headaches. Br J Clin Pharmacol 1999;48:750–755.
28.
Wilterdink JL, Easton JD: Dipyridamole plus aspirin in cerebrovascular disease. Arch Neurol 1999;56:1087–1092.
29.
Gent M: Benefit of clopidogrel in patients with coronary disease. Circulation 1997;96:I–467.
30.
Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, Kamm B: A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989;321:501–507.
31.
Steinhubl SR, Tan WA, Foody JM, Topol EJ: Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. JAMA 1999;281:806–810.
32.
Gorelick PB, Harris Y, Burnett B, Bonecutter FJ: The recruitment triangle: Reasons why African Americans enroll, refuse to enroll, or voluntarily withdraw from a clinical trial: An interim report from the African-American Antiplatelet Stroke Prevention Study (AAASPS). J Natl Med Assoc 1998;90:141–145.
33.
CAPRIE Steering Committee: A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329–1339.
34.
Bhatt DL, Hirsch AT, Ringleb PA, Hacke W, Topol EJ: Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin. Am Heart J 2000;140:67–73.
35.
Albers GW: Choice of endpoints in antiplatelet trials: Which outcomes are most relevant to stroke patients? Neurology 2000;54:1022–1028.
36.
Bhatt DL, Marso SP, Hirsch AT, Ringleb P, Hacke W, Topol EJ: Superiority of clopidogrel versus aspirin in patients with a history of diabetes mellitus. J Am Coll Cardiol 2000;35(suppl A):409.
37.
Bhatt DL, Foody JM, Hirsch AT, Ringleb P, Hacke W, Topol EJ: Complementary, additive benefit of clopidogrel and lipid-lowering therapy in patients with atherosclerosis. J Am Coll Cardiol 2000;35(suppl A):326.
38.
Bhatt DL, Hirsch AT, Chew DP, Ringleb P, Hacke W, Topol EJ: Marked superiority of clopidogrel versus aspirin in patients with a history of previous cardiac surgery. J Am Coll Cardiol 2000;35(suppl A):383.
39.
Hankey GJ: One year after CAPRIE, IST and ESPS 2: Any changes in concepts? Cerebrovasc Dis 1998;8:1–7.
40.
Nutescu E, Helgason CM: Combination of aspirin-clopidogrel therapy in patients with ischemic stroke. Stroke 2000;31:298.
41.
Bajzer CT, Kapadia SR, Yadav JS: Clopidogrel use in carotid artery stenting. Am J Cardiol 1999;84(suppl 6A):7P.
42.
Moussa I, Gishel N, Lawrence E, Iyer S, Vitek J, Al-Mubarak N, Moses J, Roubin G: Clopidogrel may enhance the clinical efficacy of carotid artery stent implantation: The EMILY Registry. Stroke 2000;31:299.
43.
Barnett HJ, Gunton RW, Eliasziw M, Fleming L, Sharpe B, Gates P, Meldrum H: Causes and severity of ischemic stroke in patients with internal carotid artery stenosis. JAMA 2000;283:1429–1436.
44.
The Abciximab in Ischemic Stroke Investigators: Abciximab in acute ischemic stroke: A randomized, double-blind, placebo-controlled, dose-escalation study. Stroke 2000;31:601–609.
45.
Wallace RC, Furlan AJ, Moliterno DJ, Stevens GH, Masaryk TJ, Perl J 2nd: Basilar artery rethrombosis: Successful treatment with platelet glycoprotein IIb/IIIa receptor inhibitor. AJNR 1997;18:1257–1260.
46.
Rote WE, Nedelman MA, Mu DX, Manley PJ, Weisman H, Cunningham MR, Lucchesi BR: Chimeric 7E3 prevents carotid artery thrombosis in cynomolgus monkeys. Stroke 1994;25:1223–1232.
47.
Nicholls SC, Olson A, Moore A, Douville C, Smith W: The evaluation of antiplatelet therapy for postoperative thromboembolism in carotid endarterectomy. Stroke 2000;31:323.
48.
Kapadia SR, Bajzer CT, Ziada KM, Silver MJ, Cura FA, L’Allier PL, Yadav JS: Initial experience of glycoprotein IIb/IIIa inhibition with abciximab during carotid stenting: A safe adjunctive therapy. J Am Coll Cardiol 2000;35:86A.
49.
Cecena FA, Hoelzinger DH, Miller JA, Abu-Shakra S: The platelet IIb/IIIa inhibitor abciximab as adjunctive therapy in carotid stenting of potential thrombotic lesions. J Intervent Cardiol 1999;12:355–362.
50.
Chew DP, Bhatt DL, Topol EJ: Increased mortality with oral glycoprotein IIb/IIIa antagonists: A pooled analysis of the large scale oral glycoprotein IIb/IIIa trials. J Am Coll Cardiol 2000;35(suppl A):393.
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