Search

Antiplatelet therapy is recommended for stroke prevention in persons with a history of thromboembolic stroke or transient ischemic attack (TIA) that is not of cardiac origin. Aspirin was the first antiplatelet agent to be used in this context and is still the most frequently prescribed preventive treatment for ischemic stroke. However, because the results of clinical studies with aspirin have been inconsistent, the dose of aspirin required for stroke prevention in persons with cerebrovascular disease has been a subject of debate among stroke neurologists. In the present discussion, low-dose aspirin is generally regarded by the experts as equivalent in effectiveness to high-dose aspirin, and its higher tolerability has the potential to significantly increase compliance with long-term therapy. Higher aspirin doses may have clinical utility in particular settings, but this requires further study. Despite the controversy, aspirin is now recognized as the treatment standard against which other antiplatelet agents are compared. Antiplatelet agents that may be more effective than aspirin have now been developed. Although each of these agents has been directly compared with aspirin in a large, randomized clinical trial, the lack of direct comparisons among these alternative antiplatelet therapies complicates decisions regarding long-term care of patients with cerebrovascular disease. An international panel of stroke neurologists reports that their selection of antiplatelet therapies for patients with prior history of TIA or stroke depends most heavily on drug efficacy and safety issues and is limited by availability (approval status of alternatives).

Objective: To review the risk and pathogenesis of stroke associated with nonvalvular atrial fibrillation (AF) and the efficacies and risks of stroke prevention strategies., Background: About 16% of ischemic strokes are associated with AF; AF is an independent risk factor for stroke., Methods: Review of the literature, focusing on 13 randomized trials of antithrombotic therapy., Results: The overall risk of stroke in AF patients averages about 5%/y, but with wide variation depending on the presence of coexistent thromboembolic risk factors. AF patients with low (about 1% per year), moderate (about 3% per year), and high (about 6% per year) stroke risks have been identified, but the generalizability of risk stratification schemes to clinical practice has not been fully assessed. AF patients with prior stroke or transient ischemic attack, even if remote, are at highest risk (about 12% per year). Adjusted-dose warfarin (target International Normalized Ratio [INR] 2-3) is highly efficacious for preventing stroke in AF patients (about 70% risk reduction) and is safe for selected patients, if carefully monitored. Aspirin has a modest effect on reducing stroke (about 20% risk reduction). The numbers of AF patients that would need to be treated with warfarin instead of aspirin for 1 year to prevent one ischemic stroke are about 200, 70, and 20 for those with low, moderate and high risk, respectively., Conclusions: Many patients with nonvalvular AF have substantial rates of ischemic stroke. Stratification of stroke risk identifies AF patients who benefit most and least from lifelong anticoagulation. Warfarin is recommended for high-risk AF patients who can safely receive it. Aspirin may be indicated for those with a low stroke risk and for those who cannot receive warfarin. For AF patients considered to have a moderate risk of stroke, individual bleeding risk during anticoagulation and patient preference should particularly influence the choice of antithrombotic prophylaxis.

There are two potential purposes for cardiac evaluation in patients with cerebrovascular disease: to identify possible cardioembolic pathophysiology for ischemic symptoms and to identify concomitant coronary artery disease. Both have important implications for patient prognosis and treatment, and testing therefore appears to be warranted. On the other hand, the cost conservation movement in medicine dictates that physicians limit unnecessary, costly, possibly risky testing when the diagnostic yield is low. For example, the overall yield of cardiac testing in "usual stroke patients" who have no suggestive history or findings on examination, chest X-ray, or electrocardiogram is less than 10% and may not be indicated routinely. Conversely, young patients with stroke of unknown cause are likely to benefit from aggressive cardiac testing. Many reported series and clinical trials have demonstrated that patients with cerebrovascular disease are more likely to die in follow-up from cardiovascular than from cerebrovascular causes. This risk is best defined and may be highest in patients with carotid disease, in whom the 5-year cardiac mortality rate may be as high as 40 to 50%. Studies have shown that such patients are also likely to have abnormal tests for cardiac ischemia, even when a history of cardiovascular events or symptoms or electrocardiographic abnormalities are lacking. These results, combined with further investigations into which cerebrovascular patients are at highest risk for cardiovascular disease and what testing best identifies underlying, treatable cardiovascular disease, are needed to direct the care and improve the cardiovascular prognosis of patients with cerebrovascular disease.

Aspirin's benefit in preventing vascular outcomes is well established. It reduces the relative risk for stroke, myocardial infarction, and vascular death by about 25% compared with placebo. Almost 10 years ago we learned that ticlopidine is more effective than aspirin (about 12% relative risk reduction for stroke or death). However, ticlopidine has important adverse effects. In 1996, the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial showed that clopidogrel, a new thienopyridine similar to ticlopidine, is also more effective than aspirin (by a similar amount) and is as safe as aspirin. Also in 1996, the European Stroke Prevention Study 2 (ESPS-2) showed that dipyridamole alone prevents stroke and that when combined with aspirin it is more effective, probably comparable to ticlopidine and clopidogrel. Dipyridamole combined with aspirin reduced the relative risk for stroke or death by about 13% compared with aspirin alone. Both clopidogrel and dipyridamole are safe but will cost more than aspirin. Aspirin also appears beneficial for acute stroke treatment. The Chinese Acute Stroke Trial (CAST) and the International Stroke Trial (IST) demonstrated that aspirin given at the time of an acute ischemic stroke reduces the risk for early death (about 5 less/1,000 treated), recurrence or death (about 10 less/1,000 treated), and dependence (about 5 less/1,000 treated). Overall, the benefits of aspirin in acute stroke treatment and stroke prevention are definite but modest. Combination therapy with antiplatelet agents that act through different mechanisms is a promising way to maximize the benefits of antiplatelet treatment.

Disinhibited, exaggerated responses to objects and environmental cues (utilization behavior) occur predominantly with frontal lobe damage. We report a striking example associated with paramedian thalamic infarction suggesting a thalamofrontal component to environmental interactions that require inhibition, self-monitoring, and cognitive flexibility.