/publications/issue/2003/2003-08/2003-08-7325

Use of Over-the-Counter Aspirin in Stroke

Author: Robert J. Hamilton, PharmD, and Eugene P. Landry, PharmD Candidate

Definition
Stroke is among the most common causes of death and disability in the United States. Stroke, or cerebrovascular accident, is described as completed if there is interruption of blood flow to the brain, causing irreversible injury. Another form of stroke is attributed to transient ischemic attack (TIA), in which local blood flow is temporarily interrupted, leading to focal neurologic deficits. Deficits longer than 24 hours in length have been used to define stroke. The other cause of stroke is subarachnoid or intracerebral hemorrhage. Pharmacotherapeutic interventions can be made in the out-patient setting to prevent recurrent TIA and to reduce the risk of further stroke.1

Incidence
Approximately 500,000 new strokes are reported annually, with nearly 150,000 stroke-related deaths.1 The most common causes of these strokes are ischemic events rather than hemorrhagic causes (the actual breakdown is 85% ischemic vs 15% hemorrhagic).2 Size, length of time of blood flow deficit, and location determine the severity of stroke and the long-lasting effects caused by the stroke.

Symptoms
Symptoms associated with stroke are highly correlated with the location in the brain in which the occlusion stops blood flow. Some common symptoms associated with specific sites are weakness or sensory loss in contralateral hemi-paresis, head/eye deviation toward the affected side, hemi-anesthesia, hemianopia, aphasia, and unawareness of the stroke event. These symptoms are seen most often in patients who have blockages in the middle cerebral artery. Posterior artery occlusions may cause visual disturbances or amnesia. Finally, vertebrobasilar artery occlusions may be responsible for the vertigo, nausea/vomiting, ataxia, or nystagmus seen in some patients.1

Diagnostic Tests
Differential diagnoses must be evaluated before a definite diagnosis of TIA can be made. Some other disease states that commonly need to be ruled out include Todd?s paralysis, hypoglycemia, migraine headache, brain tumor, drug overdose, and Bell?s palsy.1 Several tests also are utilized to identify TIA in patients and to determine or exclude its cause. In addition, the tests may assess modifiable risk factors and determine a patient?s prognosis. Typical tests include complete blood counts with differential and platelets, prothrombin time or international normalized ratio, electrocardiogram, cranial computerized axial tomography scan, and arterial imaging (arteriog-raphy). Other tests may be used for further diagnosing causes?such as transesophageal electrocardiogram and magnetic resonance imaging. Of all the tests listed, arteriog-raphy is the gold standard for defining occlusive cere-brovascular disease.1,2

Treatment
Aspirin is a salicylate with anti-inflammatory as well as antiplatelet activity. The latter effect is the main mechanism of action needed in stroke treatment. Aspirin inhibits the cyclo-oxygenase enzymes, which in turn inhibits both prostaglandin and thromboxane production. The main role of aspirin in stroke therapy is the inhibition of thromboxane A2, a potent inducer of platelet aggregation. Through this inhibition, blood clots are degraded and, to a lesser extent, prevented from forming. Multiple trials have confirmed the usefulness of aspirin in recurrent TIA patients for the reduction of stroke occurrence. Aspirin also has been shown to be an effective prophylactic agent for stroke in patients after myocardial infarction and for other cardiac abnormalities such as atrial fibrillation.2-4 Liver disease is a contraindication for aspirin use, along with allergy to aspirin or any other aspirin-like compound. Patients with asthma may be at an increased risk of developing an allergic reaction to aspirin. Alcohol may increase the occurrence of stomach ulcers. Aspirin never should be given to children because of the risk of Reye?s syndrome. Common side effects include nausea and bleeding. Less common side effects include rash, liver damage, fever, stomach ulcers, and tinnitus. Aspirin may interact unfavorably with anticoagulants, increasing the risk of bleeding; or with corticosteroids and phenylbutazone, leading to ulcers. Aspirin may counteract the efficacy of angiotensin-converting enzyme inhibitors, beta blockers, diuretics, and uric acid?eliminating agents. Antidia-betes drugs are potentiated by aspirin, which may lead to hypoglycemia at high doses.5,6 The recommended dose of aspirin is 50 to 325 mg every day for prophylax-is of stroke.1,2 An enteric-coated product is available for patients who have difficulty tolerating aspirin or are at high risk of developing ulcers. The enteric coating prevents the degradation of the tablet while it is in the stomach, thus preventing exposure of aspirin to the stomach lining. The use of this product will decrease the likelihood of developing aspirin-induced stomach ulcers.

Alternatives
Some alternatives to aspirin use are dipyridamole, ticlopidine, clopidogrel, and warfarin.4 There is a combination product (Aggrenox) containing 25 mg of aspirin and 200 mg of dipyridamole in each capsule.5-7 This combination product has been shown to be efficacious but expensive. This product and aspirin have been shown to inhibit platelets comparably at equal doses of aspirin.8 Ticlopidine is not used much any-more because of its unfavorable side-effect profile. Clopidogrel is comparable to aspirin but more expensive.7 This agent may be used if a patient is allergic to aspirin or unresponsive to therapy. A trial analyzed clopidogrel therapy versus aspirin and a combination of the 2 drugs.9 No difference could be found between these therapies. Warfarin is an anticoagulant that is the primary treatment for patients with atrial fibrillation as their primary risk factor for stroke. A trial was performed to compare aspirin and war-farin in the prevention of ischemic stroke.10 In this trial, no difference was found between the treatments, and there was no difference in bleeding risk. The evidence from all of these trials indicates that all of these drugs are valid alternatives to aspirin in stroke prevention.

Lifestyle Modifications
The reduction of modifiable risk factors through lifestyle changes is another form of treatment used along with pharmacotherapy. The main risk factors are hypertension, cigarette smoking, atrial fibrillation, elevated homocysteine levels, hyperlipidemia, diabetes mellitus, and the use of oral anticoagulants.1 Alcohol intake is a somewhat controversial subject in stroke patients. Most literature suggests that moderate alcohol intake may reduce the risk of stroke, but, as the amount of alcohol per day is increased, the effect is reversed and patients become at higher risk.1 These risk factors are all modifiable to a certain extent through some sort of clinical intervention. Exercise is another modification that may be initiated to encourage a healthier lifestyle.

Conclusion
Stroke is a very serious and prominent disorder affecting many people in this country. This disorder is not only life-threatening, but also extremely debilitating. The use of proper diagnostic procedures will assess stroke severity and will rule out other disorders that may present similarly to stroke. Early recognition and treatment are essential to decreasing complications from stroke and to reducing the incidence of recurrent TIA, which is the leading cause of stroke. In the outpatient setting, pharmacists can play a major role by guiding patients to proper therapeutic options. Aspirin is an excellent choice for such applications because of its cost, accessibility, and efficacy. Knowledge of interaction factors is vital to proper and safe administration and maintenance of this drug. Some alternatives to aspirin include Aggrenox, ticlopidine, clopidogrel, and warfarin. These therapies may be used when a patient cannot tolerate aspirin or when the indication for therapy shows a clear benefit for another agent. Along with any pharmacotherapy, risk factor reduction should always be instituted to ensure optimal therapeutic outcomes.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Ryan, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: dryan@mwc.com.