Stroke is a common cause of disability or death. A second episode of stroke or transient ischemic attack (TIA) may not be the same type as the initial event. Patients with a previous TIA or stroke are likely to have other vascular events, including myocardial infarction. Secondary prevention involves management of all of the modifiable risk factors for stroke (see accompanying table) and treating the causes of the initial episode.

Lees and associates reviewed four questions that, when answered, provide the appropriate path to secondary prevention of stroke. First, is it acute cerebrovascular disease? The key features of acute cerebrovascular disease are focal neurologic deficit, sudden onset and the absence of an alternative explanation for symptoms.

The second question asks, is it ischemic or hemorrhagic stroke? Infarction cannot be easily distinguished from intracerebral hemorrhage based solely on history and physical examination, which makes cerebral imaging essential. Immediately after the episode, computed tomographic (CT) scan identifies hemorrhage, but a few weeks after the onset of symptoms, the distinction between hemorrhage and infarction becomes difficult. Small hemorrhages may be missed after one week. Magnetic resonance imaging (MRI) is more sensitive than CT for detecting brain stem, cerebellar and small ischemic strokes. Hemorrhagic episodes are identifiable by MRI long after they become undetectable on CT.

Third, is the cause cardioembolic or vascular? An ischemic stroke caused by embolism from the heart or major blood vessels requires full anticoagulation. Transthoracic echocardiography is usually adequate, but transesophageal echocardiography is needed if the results are equivocal or the index of suspicion is high.

Finally, is the anterior or posterior circulation involved? The vertebrobasilar arteries supply the brain stem, cerebellum and occipital lobes. The cerebral hemispheres are supplied through the carotid artery.

Risk factor management includes smoking cessation, elevated blood pressure management, normalization of serum blood glucose levels in diabetic patients and lipid control with statin drugs. The use of statin drugs in patients with normal lipid levels and the reduction of elevated plasma homocysteine levels with folate and pyridoxine supplements may also be useful.

Anticoagulation with warfarin to an International Normalized Ratio (INR) of 2.0 to 3.0 is appropriate in patients with atrial fibrillation and those with other clear sources of cardiac embolism. Patients with mechanical heart valves require a target INR of 2.5 to 4.5. In all other patients with ischemic stroke, antiplatelet therapy with low-dose aspirin, or possibly an aspirin-dipyridamole combination, is first-line treatment. Dipyridamole alone does not prevent cardiac embolic events or overall mortality. Clopidogrel may be more effective than aspirin but is probably not cost-effective for initial treatment and should be reserved for use in patients with aspirin intolerance.

The authors conclude that secondary prevention of stroke requires dietary, smoking, medical and, possibly, surgical intervention. Carotid endarterectomy and, in select cases, carotid angioplasty are appropriate in patients with recent carotid area symptoms and significant ipsilateral stenosis (greater than 70 percent). The surgery should be performed by an experienced staff. Patient compliance with treatments must be monitored, as should progression of vascular disease complications in the kidneys, heart and brain.

editor's note: The fixed-dose combination of extended-release dipyridamole and aspirin (Aggrenox) combines two antiplatelet agents with different modes of action. This combination reduces thrombus formation. In patients with prior stroke or TIA, the rate of the combined end point of stroke and death is lower with this combination than with aspirin alone. The end point of death alone does not appear to be reduced by any treatment. No studies are available comparing the combination of aspirin and dipyridamole with clopidogrel, ticlopidine or anticoagulants. Adverse events are mild. The recommended dosage of the combination therapy for stroke prevention is one capsule containing 25 mg of aspirin and 200 mg of extended-release dipyridamole, two times daily. Consultants from The Medical Letter conclude that the combination in Aggrenox might be more effective than a low dose of aspirin alone in preventing stroke in patients who have had a TIA or ischemic stroke, with little additional toxicity, but it is much more expensive and has not been more effective than aspirin alone in preventing death.—r.s.