TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: Results of the TIMI 10B trial

Christopher P. Cannon, C. Michael Gibson, Carolyn H. McCabe, A. A.Jennifer Adgey, Marc J. Schweiger, Rafael F. Sequeira, Gilles Grollier, Robert P. Giugliano, Martin Frey, Hiltrud S. Mueller, Richard M. Steingart, W. Douglas Weaver, Frans Van De Werf, Eugene Braunwald

Research output: Contribution to journalArticlepeer-review

317 Scopus citations


Background - Bolus thrombolytic therapy is a simplified means of administering thrombolysis that facilitates rapid time to treatment. TNK- tissue plasminogen activator (TNK-tPA) is a highly fibrin-specific single- bolus thrombolytic agent. Methods and Results - In TIMI 10B, 886 patients with acute ST-elevation myocardial infarction presenting within 12 hours were randomized to receive either a single bolus of 30 or 50 mg TNK-tPA or front- loaded tPA and underwent immediate coronary angiography. The 50-mg dose was discontinued early because of increased intracranial hemorrhage and was replaced by a 40-mg dose, and heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rates of TIMI grade 3 flow at 90 minutes (62.8% versus 62.7%, respectively, P=NS); the rate for the 30-mg dose was significantly lower (54.3%, P=0.035) and was 65.8% for the 50-mg dose (P=NS). A prespecified analysis of weight-based TNK-tPA dosing using median TIMI frame count demonstrated a dose response (P=0.001). Similar dose responses were observed for serious bleeding and intracranial hemorrhage, but significantly lower rates were observed for both TNK-tPA and tPA after the heparin doses were lowered and titration of the heparin was started at 6 hours. Conclusions - TNK-tPA, given as a single 40-mg bolus, achieved rates of TIMI grade 3 flow similar to those of the 90-minute bolus and infusion of tPA. Weight-adjusting TNK-tPA appears to be important in achieving optimal reperfusion; reduced heparin dosing appears to improve safety for both agents. Together with the safety results from the parallel Assessment of the Safety of a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single- bolus thrombolytic agent has been identified for phase III testing.

Original languageEnglish (US)
Pages (from-to)2805-2814
Number of pages10
Issue number25
StatePublished - Dec 22 1998
Externally publishedYes


  • Myocardial infarction
  • Plasminogen activators
  • Thrombolysis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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