Early Administration of Aspirin in Patients Treated With Alteplase for Acute Ischemic Stroke: A Randomized Controlled Trial

Study Questions:

What are the effects of early addition of intravenous aspirin to alteplase with standard alteplase without aspirin?


In this multicenter, randomized, open-label trial with blind-endpoint assessment, patients with acute ischemic stroke treated with alteplase were randomly assigned to 300 mg intravenous aspirin within 90 minutes after the start of alteplase treatment, or to no additional treatment. In both groups, oral antiplatelet therapy was started 24 hours after alteplase treatment. The primary endpoint was favorable outcome, defined as a score of 0-2 on the modified Rankin scale at 3 months.


Between July 29, 2008, and April 20, 2011, 642 patients (322 patients aspirin, 320 patients standard treatment) of the targeted 800 patients were enrolled. At that time, the trial was terminated prematurely because of an excess of symptomatic intracranial hemorrhage (SICH) and no evidence of benefit in the aspirin group. At 3 months, 174 (54.0%) patients in the aspirin group versus 183 (57.2%) patients in the standard treatment group had a favorable outcome (absolute difference, −3.2%; 95% confidence interval [CI], −10.8 to 4.2; crude relative risk, 0.94; 0.82-1.09; p = 0.42). Adjusted odds ratio was 0.91 (95% CI, 0.66-1.26; p = 0.58). SICH occurred more often in the aspirin group (14 [4.3%] patients) than in the standard treatment group (five [1.6%]; absolute difference, 2.8%; 95% CI, 0.2-5.4; p = 0.04). SICH was more often the cause of poor outcome in the aspirin group compared with the standard treatment group (11 vs. 1, p = 0.006).


The authors concluded that early administration of intravenous aspirin in patients with acute ischemic stroke treated with alteplase does not improve outcome at 3 months, and increases the risk of SICH.


This study shows that intravenous administration of 300 mg aspirin within 90 minutes after start of alteplase treatment does not improve functional outcome at 3 months, but increases the risk of SICH. The trial delivers an important message that no evidence exists to suggest any additional benefit from co-administration of aspirin with intravenous alteplase, and provides support from a randomized trial for the international guidelines recommending that aspirin should not be administered within 24 hours of stroke thrombolysis.

Clinical Topics: Dyslipidemia, Lipid Metabolism

Keywords: Risk, Thrombolytic Therapy, Stroke, Intracranial Hemorrhages, Platelet Aggregation Inhibitors, Cardiology, Fibrinolytic Agents, Organization and Administration, Brain Ischemia, Tissue Plasminogen Activator

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