Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial.
OBJECTIVE
The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI).


BACKGROUND
Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established.


METHODS
Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min.


RESULTS
In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively.


CONCLUSIONS
Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.
Giugliano
Robert P
RP
TIMI Study Group, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. rgiugliano@partners.org
Roe
Matthew T
MT
Harrington
Robert A
RA
Gibson
C Michael
CM
Zeymer
Uwe
U
Van de Werf
Frans
F
Baran
Kenneth W
KW
Hobbach
Hans Peter
HP
Woodlief
Lynn H
LH
Hannan
Karen L
KL
Greenberg
Sally
S
Miller
Joanne
J
Kitt
Michael M
MM
Strony
John
J
McCabe
Carolyn H
CH
Braunwald
Eugene
E
Califf
Robert M
RM
D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000378:metabolism*; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010959:Tissue Plasminogen Activator; D000077542:Eptifibatide; D000077785:Tenecteplase