TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators.
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.


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.
Cannon
C P
CP
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02115, USA.
Gibson
C M
CM
McCabe
C H
CH
Adgey
A A
AA
Schweiger
M J
MJ
Sequeira
R F
RF
Grollier
G
G
Giugliano
R P
RP
Frey
M
M
Mueller
H S
HS
Steingart
R M
RM
Weaver
W D
WD
Van de Werf
F
F
Braunwald
E
E
D000368:Aged; D001777:Blood Coagulation; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D005343:Fibrinolytic Agents; D006493:Heparin; C104096:TNK-tissue plasminogen activator; D010959:Tissue Plasminogen Activator