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


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).
Van de Werf
F
F
Department of Cardiology, Gasthuisberg University Hospital, Leuven, Belgium. frans.vandewerf@uz.kuleuven.ac.be
Cannon
C P
CP
Luyten
A
A
Houbracken
K
K
McCabe
C H
CH
Berioli
S
S
Bluhmki
E
E
Sarelin
H
H
Wang-Clow
F
F
Fox
N L
NL
Braunwald
E
E
D000293:Adolescent; D000328:Adult; D017023:Coronary Angiography; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D012449:Safety; D015996:Survival Rate; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; C104096:TNK-tissue plasminogen activator; D010959:Tissue Plasminogen Activator