Safety assessment of single-bolus administration of TNK tissue-plasminogen activator in acute myocardial infarction: the ASSENT-1 trial. The ASSENT-1 Investigators

Am Heart J. 1999 May;137(5):786-91. doi: 10.1016/s0002-8703(99)70400-x.


Background: To evaluate the safety of several doses of a new thrombolytic, TNK tissue-plasminogen activator (tPA), given as a single bolus to patients with acute myocardial infarction.

Methods and results: A total of 3235 patients were given TNK-tPA: 1705 received 30 mg, 1457 received 40 mg, and 73 received 50 mg. The 50-mg dose was discontinued and replaced by 40 mg because of increased bleeding observed in the Thrombolysis In Myocardial Infarction (TIMI)-10B study, the phase II angiographic efficacy trial conducted in parallel with this study. The total stroke rate at 30 days in the trial was 1.5%. An intracranial hemorrhage was observed in 25 patients (0.77%): 16 in the 30-mg group (0.94%) and 9 in the 40-mg group (0.62%). No strokes occurred in the 73 patients treated with 50 mg TNK-tPA. In patients treated within 6 hours after symptom onset the rates of intracranial hemorrhage were 0.56% (30 mg TNK-tPA) and 0.58 (40 mg TNK-tPA). Death, death or nonfatal stroke, or severe bleeding complications occurred in a low proportion of patients: 6.4%, 7.4%, and 2.8%, respectively, without significant differences among the treatment groups.

Conclusions: The overall safety profile of a single bolus of 30 to 50 mg TNK-tPA is comparable to that of accelerated r-tPA observed in other large trials. The safety data from this trial and the patency data of TIMI-10B were the basis for a decision to conduct a large phase III mortality trial comparing weight-adjusted single-bolus TNK-tPA with accelerated r-tPA (ASSENT-2).

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Coronary Angiography
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use
  • Follow-Up Studies
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Retrospective Studies
  • Safety
  • Survival Rate
  • Thrombolytic Therapy / methods
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / therapeutic use
  • Treatment Outcome


  • Fibrinolytic Agents
  • TNK-tissue plasminogen activator
  • Tissue Plasminogen Activator