This study will determine the safety of 500mg of aspirin added to IV TPA at standard doses to
prevent re-occlusion of cerebral vessels after successful reperfusion. In ischemic stroke
brain arteries are occluded either by an embolus originating in the heart or large vessels
leading to the brain or by a process of acute thrombosis of the cerebral arteries over a
ruptured atherosclerotic plaque. Rupture of the plaque exposes thrombogenic elements within
the plaque and leads to accumulation and activation of platelets and induction of the
clotting cascade eventually leading to acute thrombosis and occlusion of the artery. TPA is
currently approved by the Food and Drug Administration to treat heart and brain problems
caused by blockage of arteries. It activates plasminogen and leads to disintegration of the
thrombus/embolus. It is effective only if begun within 3 to 4.5 hours of onset of the stroke
because of potential deleterious side effects including life threatening symptomatic
intracranial hemorrhage (sICH) when the drug is administered outside of this time window.
Reperfusion of the ischemic brain (i.e. timely opening of the occluded artery) with TPA is
associated with improved outcome. However, in about 33% of patients that have successfully
reperfused after TPA the artery re-occludes within the first few hours resulting in worsening
neurological symptoms and worse functional outcome. This re-occlusion is speculated to result
from re-thrombosis over an existing ruptured atherosclerotic plaque. This is explained by the
relatively short half life of TPA leaving the exposed ruptured plaque intact which leads to
re-activation of platelets and clotting factors and re-thrombosis. Thus, we hypothesize that
the addition of an antiplatelet agent to TPA would result in lower rates of re-occlusion
after AIS. The FDA approved TPA for patients with AIS but discouraged the concomitant use of
anti-platelet or anti-thrombotic drugs for the first 24hours after administration of TPA
because of concerns that such therapy may result in increased rates of intracerebral
hemorrhage. Aspirin is a well known platelet anti-aggregant that works by inhibition of
cycloxygenase 1 and reduction in thromboxane A levels. It has a rapid onset of action and
additional potential beneficial anti-inflammatory effects in patients with AIS. The
international stroke study showed that acute treatment of stroke patients with 500mg of
aspirin is safe and feasible and results in better outcome. Furthermore, the drug was safe in
these circumstances with an ICH rate of only .
Therefore, the purpose of this clinical trial is to examine the safety and efficacy of the
combination of aspirin with rt-TPA in patients with AIS.