Antiplatelet Therapy for Secondary Prevention of Stroke

Thu, 3/5/09 - 11:08am
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Author(s):

Adel Alhazzani, MD, Magdy H. Selim, MD, PhD, Richard Goddeau, Jr., DO, and Louis R. Caplan, MD

author affiliations:

From the Division of Cerebrovascular Diseases, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

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Stroke is a leading cause of death and disability in the United States and worldwide. It preferentially affects older adults and has high risk of recurrence. Because of the aging population, the burden will increase greatly; thus, the need for secondary prevention strategies is crucial. Antiplatelet therapy remains paramount in prevention of recurrent vascular events following stroke or transient ischemic attack. Aspirin, clopidogrel, and the combination of aspirin plus extended-release dipyridamole are all effective in reducing the risk of recurrent vascular events. The use of either clopidogrel or the combination of aspirin plus extended-release dipyridamole may be more effective than aspirin alone for secondary stroke prevention. Current guidelines endorse any of these antiplatelet agents (including aspirin) as appropriate treatment options. Choosing antiplatelet agents must be tailored according to patient characteristics, cost, and tolerability. (Annals of Long-Term Care: Clinical Care and Aging 2009;17[3]:13-17)

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Introduction

Stroke is a leading cause of death and disability in the United States and worldwide. Each year, about 795,000 people have a stroke in the United States, and close to 25% of them (185,000) are recurrent attacks.1 The economic consequences of stroke are substantial. The estimated direct and indirect cost of stroke in 2009 is $68.9 billion.1

Patients who have experienced a cerebrovascular event are at high risk of a recurrence, as well as an increased risk of myocardial infarction (MI) and sudden cardiac death.2,3 Given the higher risk of stroke in older people, the need for secondary prevention is even greater to decrease the burden of cerebrovascular diseases. Antiplatelet therapy remains a cornerstone to preventing recurrent vascular events in symptomatic cerebrovascular disease.

In this article, we review the evidence from randomized trials for established and emerging antiplatelet therapies for secondary stroke prevention, and provide evidence-based recommendations for their use.

Efficacy of Antiplatelet Therapies

Since the early 1990s, the role of antiplatelet therapy in reducing the risk of recurrent vascular events in patients with a history of stroke or transient ischemic attack (TIA) has become increasingly clear. The Antiplatelet and Antithrombotic Trialists’ collaboration4 analyzed 195 randomized clinical trials (144,051 patients) comparing antiplatelet therapy with placebo in the prevention of stroke, MI, and vascular death among patients with an increased risk of occlusive vascular disease. Patients treated with an antiplatelet agent (primarily aspirin) had a 25% relative risk reduction (RRR) in nonfatal stroke as compared with placebo. The benefit of antiplatelet therapy was independent of sex, age (greater or less than 65 yr), diabetes, or hypertension. In a subset of patients with prior stroke/TIA, the odds reduction was 22%.

On the other hand, stopping antiplatelet therapy in high-risk patients increases the risk of stroke.5,6 Aspirin, the combination of aspirin with extended-release (ER) dipyridamole, clopidogrel, and others have been studied separately and have been shown to provide effective secondary prevention for patients after ischemic stroke; some will be discussed in this review.

Aspirin

Aspirin is the first agent to be used for secondary stroke prevention and remains the most commonly prescribed. Its antiplatelet properties relate to the irreversible inhibition of the enzyme cyclooxygenase, which in turn reduces production of thromboxane A2 (stimulator of platelet aggregation).

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