The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico II (GISSI-2), and The International Study Group

N Engl J Med. 1992 Jul 2;327(1):1-6. doi: 10.1056/NEJM199207023270101.


Background: Many trials in patients with acute myocardial infarction have demonstrated that thrombolytic therapy is not associated with an excessive risk of stroke, as compared with conventional treatment. However, the incidence of various forms of stroke in patients treated with different thrombolytic and antithrombotic regimens and the associated effect of risk factors for stroke are largely unknown.

Methods: Strokes occurring in patients hospitalized with acute myocardial infarction who were enrolled in either of two large trials were analyzed. The patients were randomly assigned to receive streptokinase (1.5 million units) or recombinant tissue plasminogen activator (t-PA) (100 mg) and also randomly assigned to receive subcutaneous heparin or no heparin. Ninety-one percent of the patients also received aspirin.

Results: Complete data were available on 20,768 patients. A total of 236 (1.14 percent) had strokes in the hospital; 0.36 percent had hemorrhagic strokes, 0.48 percent ischemic strokes, and 0.30 percent strokes of undefined cause. Patients treated with t-PA had a small but significant excess of stroke as compared with those who received streptokinase (1.33 vs. 0.94 percent; adjusted odds ratio, 1.42; 95 percent confidence interval, 1.09 to 1.84). The administration of subcutaneous heparin in addition to a thrombolytic agent did not increase the risk of stroke (risk with heparin, 1.13 percent; without heparin, 1.14 percent). Older age, a higher Killip class, and the occurrence of anterior infarction significantly increased the risk of stroke, whereas a higher body-mass index or a history of hypertension, diabetes, or smoking did not.

Conclusions: Patients with acute myocardial infarction who receive thrombolytic therapy have a small risk of stroke. Treatment with t-PA as compared with streptokinase resulted in a small but significant excess of stroke. Subcutaneous heparin, given together with t-PA or streptokinase and aspirin, did not result in an increased risk of stroke.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Brain Ischemia / chemically induced
  • Cerebral Hemorrhage / chemically induced
  • Cerebrovascular Disorders / chemically induced*
  • Drug Therapy, Combination
  • Female
  • Heparin / administration & dosage
  • Heparin / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Random Allocation
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Risk
  • Streptokinase / administration & dosage
  • Streptokinase / adverse effects
  • Thrombolytic Therapy / adverse effects*
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / adverse effects


  • Recombinant Proteins
  • Heparin
  • Streptokinase
  • Tissue Plasminogen Activator
  • Aspirin