Each year about 700,000 Americans sustain a stroke, and about 29% of those patients who are aged 65 years or older die within 1 year. Worldwide, stroke is the third leading cause of death and the leading cause of severe disability in adults.1
Substantial advances have been made in recent decades in understanding the mechanisms of stroke and its risk factors and in developing therapies.2 Because thrombosis plays an important role in the pathogenesis of ischemic stroke, drugs that interfere with hemostasis and clot formation, such as anticoagulants and platelet aggregation inhibitors, commonly are used to manage cerebrovascular disease.
In this article, we review the efficacy and safety of aspirin, ticlopidine, clopidogrel, and aspirin/extended-release dipyridamole in the secondary prevention of atherothrombotic stroke.
PRIMARY STROKE PREVENTION
Primary stroke prevention requires a comprehensive multidisciplinary approach. The first objective is to identify and modify stroke risk factors, including hypertension; diabetes mellitus; myocardial infarction (MI); hyperlipidemia; atrial fibrillation; asymptomatic carotid stenosis; and lifestyle factors, such as smoking, alcohol use, and sedentary lifestyle.3 In addition to risk factor modification, attention has recently focused on the role of aspirin in primary stroke prevention, given its well-established efficacy in the primary prevention of MI4 (specifically, the American Heart Association guidelines recommend aspirin at a dosage of 75 mg/d for cardiovascular prophylaxis for persons whose 10-year risk of a coronary event is 10% or greater).5
In persons at low risk for vascular disease, the data supporting the role of aspirin in primary stroke prevention are scant. A meta-analysis of 5 randomized trials, which included more than 50,000 participants, revealed no difference in the incidence of stroke between low-risk patients randomized to receive aspirin and those randomized to receive placebo during an average follow-up of 4.6 years. Regular use of aspirin significantly increased the rate of intracranial hemorrhage by a relative risk of 1.35.6
In the Women's Health Study, 39,876 asymptomatic women older than 44 years were randomized to receive 100 mg of aspirin or placebo on alternate days and then followed up for 10 years for a first major vascular event (nonfatal MI, nonfatal stroke, or cardiovascular death).7 Investigators found a nonsignificant 9% reduction for the primary end point but a significant 17% relative risk reduction for ischemic stroke. The most consistent benefit was for women aged 65 years or older, among whom the risk of major cardiovascular events was reduced by 26%, including a 30% relative risk reduction in ischemic stroke. There was, however, only a trend in the relative reduction of the overall risk of ischemic and hemorrhagic stroke because of an increased risk of brain hemorrhage in these elderly women.
At present, no evidence supports the use of aspirin to prevent stroke in low-risk asymptomatic persons.6,8,9 Recent guidelines from the American Heart Association/American Stroke Association Stroke Council state that aspirin can be useful for cardiovascular (including but not specific to stroke) prophylaxis in high-risk patients and for prevention of a first stroke among women whose risk is sufficiently high to outweigh the risks associated with treatment.3
Secondary Prevention of Stroke
The goal of therapy in patients who have sustained a stroke or transient ischemic attack (TIA) is to prevent recurrent cerebrovascular events. Longitudinal studies of patients with a history of ischemic stroke show that the rate of stroke recurrence ranges from 5% to 14% in the first year, and from 25% to 40% within 5 years, after the initial event.10 The risk of mortality also increases over time.
The approach to secondary prevention includes risk factor modification, medical therapy, and surgery, if appropriate. The most effective approach depends on the cause of the first cerebral ischemic event. Patients at high risk for recurrent cardioembolic stroke (ie, those with atrial fibrillation) are best managed with warfarin, barring any medical contraindications. Patients who are not candidates for anticoagulation and who do not have surgically correctable cerebrovascular disease may benefit from antiplatelet therapy.
Antiplatelet agents. The use of these agents to treat TIA and stroke has become widespread. Studies support the efficacy of aspirin, ticlopidine, clopidogrel, and dipyridamole. The selection of an agent is based on relative efficacy, availability, cost, and adverse effects (Table).
Aspirin. This is the most widely used and studied antiplatelet agent. It inhibits platelet aggregation by irreversibly blocking cyclooxygenase, essential for the synthesis of thromboxane A2, which promotes vasoconstriction and platelet activation.
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