Antiplatelet Therapy in Acute Cerebral Ischemia

Abstract

Background-Improved recognition of stroke signs and symptoms has paralleled the development of pharmacological strategies that may be examined to reduce stroke mortality and morbidity. Presently, tissue plasminogen activator is the only therapy that significantly improves outcome in acute stroke, with no agent demonstrating a significant reduction in mortality. Summary of Review-Antiplatelet agents are a heterogenous class of drugs that have been successfully used for more than 2 decades in secondary stroke prevention. These agents include aspirin, with or without dipyridamole, and more recently, the adenosine antagonists ticlopidine and clopidogrel. However, studies of the use of antiplatelet agents within 48 hours of the ictus have examined only aspirin. Only 1 study, the Multicentre Acute Stroke Trial-Italy (MAST-I), entered patients within 6 hours of the ictus. These data suggest that an improvement in mortality may be related to the speed of administration. No significant adverse events were noted with early antiplatelet monotherapy. However, MAST-I did note a significant increase in early mortality in patients receiving aspirin plus streptokinase, a finding not adequately explained by an increase in the intracranial hemorrhage rate. Conclusions-The use of antiplatelet therapy in acute stroke, clinical or experimental, has only recently received attention.It is likely that the use of antiplatelet agents for acute stroke therapy will be less restrictive than that currently seen for thrombolytics. Future studies should include an examination of those agents that have previously demonstrated efficacy in secondary stroke prevention, most notably, aspirin. The recognition that all platelet stimuli share a final common pathway that is dependent on the surface glycoprotein IIb/IIIa (fibrinogen) receptor has resulted in the development of various agents which block this receptor and are currently the focus for clinical trials. The role of nitric oxide in stroke therapy will depend on minimizing the hypotensive side effects of this agent. Stroke models are needed to provide preliminary data on the efficacy of antiplatelet therapy, especially as relates to the interaction of antiplatelet agents with thrombolytics. (Stroke. 1999;30:887-893.)

Indications for Early Aspirin Use in Acute Ischemic Stroke

“…Indeed, given that aspirin has been shown to be effective in the long-term secondary prevention of stroke after hospital discharge, 1 the prompt initiation of aspirin would also be of net benefit even for patients who present Ͼ48 hours after the onset of their symptoms. This conclusion is in accord with that of a recent review 17 of antiplatelet therapy in acute cerebral ischemia (which, however, mistakenly suggested that CAST and IST did not enter patients within the first 6 hours).…”

“…In summary, the present overview of 2 large randomized trials with Ϸ40 000 patients shows that early aspirin is beneficial in a wide range of patients with suspected acute ischemic stroke, confirming 17,21 that such treatment should routinely be considered for all patients who present with signs and symptoms of acute ischemic stroke, provided that no strong contraindications are apparent and that hemorrhagic stroke can be excluded with reasonable probability (with or without prior CT scan).…”

“…16,17 The patients in these 2 trials were all randomized within 48 hours of the onset of symptoms, with definite benefit for those entered either 0 to 24 or 25 to 48 hours from the onset. The second of the results does not, however, provide any good reason to delay the start of aspirin promptly in patients who present early (particularly because the incidence of hemorrhagic stroke or transformation was low during days 0 to 1, whereas that of recurrent ischemic stroke was relatively high), but it does mean that even patients who present somewhat later can still benefit from prompt treatment.…”

A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window

“…The only preventive treatment of stroke is antiplatelet therapy for patients with transient ischemic attack or stroke, which produces a modest but clinically worthwhile benefit (3). In acute stroke, only a small fraction of patients benefit from intravenous administration of recombinant tissue plasminogen activator, which is the only drug with proven effectiveness in reducing the size of infarct in humans (4,5). Even though a large number of different compounds have been proven to reduce the size of brain infarct in animal studies, replication of the experiments with the neuroprotectives in humans have regularly failed.…”

Update on Clinical Trials of Antiplatelet Therapy for Cerebrovascular Diseases

“…These trials suggest that approximately 5 early deaths can be prevented per 1,000 patients treated [22]. Nevertheless, the combination of aspirin for acute ischemic stroke, especially with thrombolytics, has not been uniformly endorsed [23]. …”