Management of Ischemic Stroke in Geriatric Patients: Aspirin
Aspirin is the most widely used agent for the prevention of secondary stroke. The An-tiplatelet Trialists studied the effect of an-tiplatelet agents in more than 73,000 elderly patients with stroke and TIAs, unstable angina, and myocardial infarction as well as patients at high risk for other events of atherosclerotic ori-gin. Antiplatelet agents, as a whole, reduced the odds of nonfatal stroke in high-risk patients by approximately 30%. Patients with a prior history of stroke and who received antiplatelet therapy experienced a 22% lower incidence of recurrent stroke or TIA. Specifically, aspirin reduced the combined risk of stroke, myocar-dial infarction, or vascular death by 25%.
Although the most effective dose of aspirin in preventing stroke remains controversial, dose-comparison studies (the Dutch TIA Trial, the European Stroke and Prevention Study [ESPS II]) suggest that high doses (1,300 mg/day) do not provide additional benefit over lower doses (50 to 325 mg/day) for secondary prevention. At low doses, aspirin inhibits the formation of thromboxane A2, consequently inhibiting platelet aggregation. The Food and Drug Administration (FDA) currently recommends aspirin (50 to 325 mg daily) for stroke prevention.
The most common adverse effects observed with aspirin are gastrointestinal ulcerations and bleeding. Patients with stroke events who are receiving aspirin therapy have no evidence-based antiplatelet alternative. Various approaches have been used in clinical practice, such as changing to an alternative antiplatelet agent, adding a different antiplatelet agent to an aspirin regimen, and switching to anticoagulation therapy.
Hydrochloride, a thienopyridine, was developed as an alternative antiplatelet in aspirin-intolerant patients experiencing TIAs or strokes. The Ticlopidine Aspirin Stroke Study (TASS), which compared ticlopidine (250 mg twice daily) to aspirin (650 mg twice daily), reported a significant risk reduction for stroke (21%) over aspirin-treated patients. Even though ticlopidine was more effective than aspirin, it is less commonly used because of its severe hematological side effects, including neutropenia, thrombo-cytopenia, and thrombotic thrombocytopenia purpura (TTP).
Ticlopidine has largely been replaced with the thienopyridine derivative. Clopidogrel inhibits platelet aggregation by modifying the platelet ADP receptor to prevent binding of the platelet to its receptor. As a result, the glycoprotein IIb/IIIa complex is inactivated. The CAPRIE Trial (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) compared clopidogrel (75 mg daily) and aspirin (325 mg daily) in reducing the risk of is-chemic stroke, myocardial infarction, or vascular death in more than 19,000 patients (more than 6,000 with a stroke history). Clopidogrel was more effective than aspirin in reducing the combined risk of ischemic stroke, myocardial infarction, or vascular death (annual risk, 5.3% and 5.8%, respectively). Clopidogrel canadian is the agent of choice for patients who cannot tolerate aspirin or in whom it is contraindicated, and it may be more effective than aspirin in patients after coronary surgery. The overall side effect profile is similar to that of aspirin.
Dipyridamole as a single agent is no more effective than aspirin (50 mg/day) for the prevention of ischemic stroke. In the ESPS II trial, however, aspirin (25 mg twice daily) was compared to placebo, extended-release canadian dipyridamole (200 mg twice daily), and the combination of extended-release dipyridamole plus aspirin (200 mg/25 mg twice daily) in more than 6,600 patients with a history of stroke or TIA for a follow-up of 2 years. Combination therapy demonstrated an additive risk reduction for stroke recurrence over the individual antiplatelet agents (18%, 16%, and 37%, respectively). In the ESPS II trial, there was a 23% reduction for combination therapy, compared with aspirin alone, for fatal and nonfatal stroke.
Table 4 Guidelines for Treatment of Acute Ischemic Stroke
|3 Hours of Symptom Onset||3 to 6 Hours of Symptom Onset||Thrombolytic Ineligibility|
|Administer tPA 0.9 mg/kg; max dose, 90 mg with 10% as initial bolus then remainder over 1 hour||Administer tPA only in selected patients (occlusion of middle cerebral artery)||Avoid full dose anticoagulation in unselected patients|
|Maintain blood pressure below 180/105 mm Hg||tPA not generally recommendedif time of symptom onset is unknown
or has been greater than 3 hours
|Aspirin 160-325 mg within 48 hours of stroke onset|
|Avoid antithrombotic agents for 24 hours following thrombolytic administration||Low-dose subcutaneous heparin or low-molecular-weight heparin for prophylaxis of deep vein thrombosis|
|Early anticoagulation is warranted for patients with acute cardioembolic stroke|
|Data from Albers GW, et al. Chest 200I;II9:300S-320S. tPA = tissue plasminogen activator.|
Table 4 summarizes the recommendations of the Sixth American College of Chest Physicians Conference on Antithrombotic Therapy for the treatment of ischemic stroke. The emphasis of treatment depends on the time frame in which patients present to health care providers with symptoms. The guidelines recommend strict adherence to inclusion and exclusion criteria as well as supervision by a physician with expertise in stroke management and in CT scan interpretation.
Table 5 summarizes recommendations for preventing stroke. In addition, several other well-documented, modifiable risk factors should be considered as ways to lower the risk for recurrent stroke. Interventions should be taken to control hypertension, encourage smoking cessation, ensure tight glycemic control in diabetes, achieve target low-density-lipoprotein concentrations, and provide warfarin for patients with atrial fibrillation. Patients should be encouraged to eat nutritious diets consisting of at least five servings of fruits and vegetables daily, to consume alcohol in moderation (no more than two drinks per day in men and one drink per day in nonpregnant women), and to incorporate approximately 30 minutes of moderate-intensity exercise three to four times weekly.
Table 5 Recommendations for Prevention of Ischemic Stroke
• Initial preventive treatment for noncardioembolic strokes
– Aspirin 50-325 mg daily
– Aspirin + extended-release 25/200 mg b.i.d.
– Clopidogrel 75 mg daily
• Initial preventive treatment for cardioembolic strokes
– Warfarin (goal INR 2.0-3.0) in patients with atrial
Optimize Disease State Management
• Sickle cell disease
• Smoking cessation
• Weight reduction in overweight patients
• Regular exercise
• Healthy diet
• Alcohol moderation
• Recommended daily amounts of folic acid and vitamins B6 and BI2
Geriatric patients are at increased risk of cerebrovascular disease and should be closely evaluated for interventions to lower their relative risk for future events. Immediate treatment of stroke is essential to limiting disability; lifestyle modifications and disease management should be included in the secondary prevention of cerebrovascular events.