New perspectives on the pharmacotherapy of ischemic stroke

Objective: To provide an overview of the impact of ischemic stroke and the steps that can be taken to reduce its burden through greater awareness of the disease, improved diagnosis and better treatment, with emphasis on the use of antiplatelet agents. Data Sources: Recent (1995-2003) published scientific literature, as identified by the authors through Medline searches, using the terms stroke, transient ischemic attack, cerebrovascular disease, atherothrombosis, risk factors, pharmacotherapy, prevention, and reviews on treatment. Study Selection: Recent systematic English-language review articles and reports of controlled randomized clinical trials were screened for inclusion. Data Synthesis: Ischemic stroke is generally the result of an atherothrombotic process leading to vessel obstruction or narrowing. Of the two types of ischemic stroke, thrombotic stroke is caused by a thrombus that develops within the cerebral vasculature, while embolic stroke arises from a distant embolus that lodges in a cerebral artery. The neurologic manifestations of stroke depend on the location of injury in the brain and the degree of ischemia or infarction. Symptoms may be reversible or irreversible and range from sensory deficits to hemiplegia. Risk factors for development of ischemic stroke include hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, prior stroke, and transient ischemic attack. Tissue plasminogen activator is currently the only available drug treatment for acute ischemic stroke. Stroke recurrence rates are high (about 40% over 5 years), and all ischemic stroke patients should receive antithrombotic therapy (unless contraindicated) for secondary prevention. Of the oral antiplatelet therapies, aspirin, clopidogrel (Plavix - Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership), and the extended-release dipyridamole plus aspirin combination are acceptable first-line agents, while anticoagulants (warfarin) are preferred in patients with atrial fibrillation. Conclusion: Lifestyle changes and drug therapy are important components of primary and secondary prevention strategies in ischemic stroke. Risk factors such as elevated blood pressure and high cholesterol should be aggressively treated. Antiplatelet agents, antihypertensive agents, and cholesterol-lowering agents are therapeutic cornerstones for secondary prevention.