Stroke is a common public health problem. About 25% of strokes are recurrent ones. Stroke subtype should be defined to determine the best evidence-based antithrombotic treatment option for preventing recurrent stroke. When choosing an antiplatelet agent for this purpose, clinicians should take into account cost, side effect profile, medical comorbidity, and patient preference.
To prevent recurrent stroke, aspirin alone (50–325 mg/d), a combination of aspirin (25 mg) plus extended-release dipyridamole (200 mg), given twice daily, or clopidogrel (75 mg/d) may be used as initial treatment. Aspirin is an efficacious, relatively safe, widely available, inexpensive, and easy-to-use antiplatelet agent. Current evidence suggests that administration of low-dose aspirin (< 325 mg/d or < 100 mg/d in various studies) is at least as efficacious as higher-dose aspirin (eg, > 325 mg/d) but is safer. The combination of aspirin plus extended-release dipyridamole is more efficacious than low-dose aspirin alone (eg, 50 or 75 mg/d) in preventing recurrent stroke.
Clopidogrel (75 mg/d) may be more efficacious than aspirin alone (325 mg/d) for prevention of recurrent stroke. Clopidogrel is a prodrug that must be converted in the liver to its active metabolite by cytochrome P450 enzymes. Certain polymorphisms (eg, CYP2C19) may prevent this conversion and lead to failure of clopidogrel to prevent major cardiovascular events.
In patients with well-controlled or treated cardiovascular risk factors, aspirin plus extended-release dipyridamole and clopidogrel may provide similar results in preventing recurrent stroke, but aspirin plus extended-release dipyridamole may be associated with a slightly higher risk of major hemorrhage. Careful control of vascular risk factors is an important strategy for prevention of recurrent stroke, and blood pressure control reduces the risk of both brain hemorrhage and infarction.
Prasugrel, a new thienopyridine derivative, more quickly and consistently inhibits platelets than clopidogrel. In stroke patients, prasugrel may be associated with a higher risk of brain hemorrhage, so it may not be indicated when there is a history of cerebrovascular disease.
Gorelick PB: Use of antiplatelet agents for the prevention of first and recurrent stroke. American Academy of Neurology CONTINUUM 2005, 11(4):77–96.Google Scholar
Craven LL: Prevention of coronary and cerebral thrombosis. Miss Valley Med J 1956, 78:213–215.PubMedGoogle Scholar
The Canadian Cooperative Study Group: A randomized trial of aspirin and sulfinpyrazone in threatened stroke. N Engl J Med 1978, 299:53–59.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Hass WK, Easton JD, Adams HP Jr, et al.: 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.PubMedGoogle Scholar
Gorelick PB, Richardson D, Kelly M, et al.; African American Antiplatelet Stroke Prevention Study Investigators: Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. JAMA 2003, 289:2947–2957.CrossRefPubMedGoogle Scholar
CAPRIE Steering Committee: A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996, 348:1329–1339.CrossRefGoogle Scholar
Diener H-C, 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.CrossRefPubMedGoogle Scholar
Mega JL, Close SL, Wiviott SD, et al.: Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009, 360:354–362.CrossRefPubMedGoogle Scholar
Wiviott SD, Braunwald E, McCabe CH, et al.: Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007, 357:2001–2015.CrossRefPubMedGoogle Scholar
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.CrossRefPubMedGoogle Scholar
The ESPRIT Study Group: Aspirin plus dipyridamole versus aspirin alone after cerebral ischemia of arterial origin (ESPRIT): randomized controlled trial. Lancet 2006, 367:1665–1673.CrossRefGoogle Scholar
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.CrossRefPubMedGoogle Scholar
Adams RJ, Albers G, Alberts MJ, et al.: Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 2008, 39:1647–1652.CrossRefPubMedGoogle Scholar
Albers GW, Amarenco P, Easton JD, et al.: Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008, 133(6 Suppl):630S–669S.CrossRefPubMedGoogle Scholar
Farrell B, Godwin J, Richards S, Warlow C: The United Kingdom Transient Ischaemic Attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991, 54:1044–1054.CrossRefPubMedGoogle Scholar
The Dutch TIA trial: protective effects of low-dose aspirin and atenolol in patients with transient ischemic attacks or nondisabling stroke. The Dutch TIA Study Group. Stroke 1988, 19:512–517.Google Scholar
Swedish Aspirin Low-Dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. The SALT Collaborative Group. Lancet 1991, 338:1345–1349.Google Scholar
Chen Z, Sandercock P, Pan H, et al.: Indications for early aspirin use in acute ischemic stroke. A combined analysis of 40,000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial. Stroke 2000, 31:1240–1249.PubMedGoogle Scholar
Gotoh F, Tohgi H, Hirai S, et al.: Cilostazol stroke prevention study: a placebo-controlled double-blind trial for secondary prevention of cerebral infarction. J Stroke Cerebrovasc Dis 2000, 9:147–157.CrossRefGoogle Scholar
Culebras A, Rotta-Escalante R, Dominguez R, et al.: Triflusal vs aspirin for prevention of cerebral infarction. A randomized study. Neurology 2004, 62:1073–1080.PubMedGoogle Scholar
Matias-Guiu J, Ferro JM, Alvarez-Sabin J, et al.: Comparison of triflusal and aspirin for prevention of vascular events in patients with cerebral infarction. The TACIP study: a randomized, double-blind, multicenter trial. Stroke 2003, 34:840–848.CrossRefPubMedGoogle Scholar