CLINICAL STUDY: ACUTE CORONARY SYNDROMES/INFARCTION
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 urial
Robert P. Giugliano, MD, SM, FACC* ,*,
Matthew T. Roe, MD, MHS, FACC ,
Robert A. Harrington, MD, FACC,
C. Michael Gibson, MS, MD, FACC*,
Uwe Zeymer, MD ,
Frans Van de Werf, MD, PhD||,
Kenneth W. Baran, MD, FACC¶,
Hans-Peter Hobbach, MD#,
Lynn H. Woodlief, MS,
Karen L. Hannan, BA,
Sally Greenberg, PhD**,
Joanne Miller, BS**,
Michael M. Kitt, MD**,
John Strony, MD, FACC,
Carolyn H. McCabe, BS*,
Eugene Braunwald, MD, FACC*,
Robert M. Califf, MD, FACC the INTEGRITI Investigators
* TIMI Study Group, Boston, Massachusetts, USA
Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Duke Clinical Research Institute, Durham, North Carolina, USA
Klinikum Kassel, Kassel, Germany
|| Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium
¶ St. Paul Heart Clinic, St. Paul, Minnesota, USA
# St. Marienkrankenhaus Siegen, Siegen, Germany
** Millennium Pharmaceuticals, Inc., South San Francisco, California, USA
Schering Plough Research Institute, Kenilworth, New Jersey, USA
Manuscript received July 15, 2002;
revised manuscript received October 25, 2002,
accepted November 11, 2002.
* Reprint requests and correspondence: Dr. Robert P. Giugliano, TIMI Study Group, 350 Longwood Avenue, 1st Floor Offices, Boston, Massachusetts 02115, USA.
rgiugliano{at}partners.org
OBJECTIVES: 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 µg/kg bolus, 2 µg/kg/min infusion, and 180 µg/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.
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Abbreviations and Acronyms
| | aPTT | | activated partial thromboplastin time | | CABG | | coronary artery bypass graft surgery | | cTFC | | corrected Thrombolysis In Myocardial Infarction frame count | | ICH | | intracranial hemorrhage | | INTEGRITI | | Integrilin and Tenecteplase in Acute Myocardial Infarction trial | | MI | | myocardial infarction | | PCI | | percutaneous coronary intervention | | STEMI | | ST-elevation myocardial infarction | | TIMI | | Thrombolysis In Myocardial Infarction | | TMPG | | Thrombolysis In Myocardial Infarction myocardial perfusion grade | | TNK | | tenecteplase |
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