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

Citation
Cp. Cannon et al., TNK tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction - Results of the TIMI 10B trial, CIRCULATION, 98(25), 1998, pp. 2805-2814
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
98
Issue
25
Year of publication
1998
Pages
2805 - 2814
Database
ISI
SICI code
0009-7322(199812)98:25<2805:TTPACW>2.0.ZU;2-U
Abstract
Background-Bolus thrombolytic therapy is a simplified means of administerin g thrombolysis that facilitates rapid time to treatment. TNK-tissue plasmin ogen activator (TNK-tPA) is a highly fibrin-specific single-bolus thromboly tic agent. Methods and Results-In TIMI 10B, 886 patients with acute ST-elevation myoca rdial infarction presenting within 12 hours were randomized to receive eith er 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 becau se of increased intracranial hemorrhage and was replaced by a 40-mg dose, a nd heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rat es 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) a nd was 65.8% for the 50-mg dose (P=NS). A prespecified analysis of weight-b ased TNK-tPA dosing using median TIMI frame count demonstrated a dose respo nse (P=0.001). Similar dose responses were observed for serious bleeding an d 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. W eight-adjusting TNK-tPA appears to be important in achieving optimal reperf usion; reduced heparin dosing appears to improve safety for both agents. To gether with the safety results from the parallel Assessment of the Safety o f a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single-bolus thrombolytic agent has been identified for phase III testing.