Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial

Lancet. 2012 Aug 25;380(9843):731-7. doi: 10.1016/S0140-6736(12)60949-0. Epub 2012 Jun 28.


Background: Thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. After alteplase-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after alteplase could reduce the risk of reocclusion and improve outcome. We compared the effects of early addition of intravenous aspirin to alteplase with standard alteplase without aspirin.

Methods: In this multicentre, randomised, open-label trial with blind-endpoint assessment, patients with acute ischaemic stroke treated with alteplase were randomly assigned to 300 mg intravenous aspirin within 90 min after start of alteplase treatment or to no additional treatment. In both groups, oral antiplatelet therapy was started 24 h after alteplase treatment. The primary endpoint was favourable outcome, defined as a score of 0-2 on the modified Rankin scale at 3 months. This trial is registered with the Netherlands Trial Register (NTR822).

Findings: 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 haemorrhage (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 favourable outcome (absolute difference -3·2%, 95% CI -10·8 to 4·2; crude relative risk 0·94, 0·82 to 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).

Interpretation: Early administration of intravenous aspirin in patients with acute ischaemic stroke treated with alteplase does not improve outcome at 3 months and increases the risk of SICH. The results of this trial do not support a change of the current guidelines, which advise to start antiplatelet therapy 24 h after alteplase.

Funding: The Dutch Heart Foundation.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Early Termination of Clinical Trials
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Infusions, Intravenous
  • Intracranial Hemorrhages / chemically induced*
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Prospective Studies
  • Secondary Prevention
  • Stroke / drug therapy*
  • Stroke / mortality
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Treatment Outcome


  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Tissue Plasminogen Activator
  • Aspirin