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
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Figure 1 Study schema. In dose-finding Part 1 (top, A), all patients received the same double-bolus regimen of eptifibatide (180/2/90) and were administered, in a randomized fashion, either half (0.27 mg/kg) or three-quarters (0.40 mg/kg) of the standard dose of tenecteplase (TNK). After completion of Part 1, all patients in Part 2 (bottom, A) received half-dose tenecteplase, whereas the second bolus dose of eptifibatide was randomly assigned (90 vs. 180 µg/kg). On the basis of the dose-finding results, the combination of eptifibatide 180/2/180 plus half-dose tenecteplase was selected for direct comparison to standard-dose tenecteplase in dose-confirmation (B). ACC/AHA = American College of Cardiology/American Heart Association; TIMI 3 = Thrombolysis In Myocardial Infarction grade 3 flow.
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Figure 2 Rates of Thrombolysis In Myocardial Infarction (TIMI) grade 2 and 3 flow in the infarct artery 60 min after administration of tenecteplase (TNK) in dose-finding (A) and dose-confirmation (B). The last bar on the right in B represents pooled data for all patients receiving eptifibatide 180/2/180 and half-dose TNK in both dose-finding and confirmation phases.
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Figure 3 Corrected Thrombolysis In Myocardial Infarction (cTFC) frame count for all patients receiving half-dose tenecteplase (TNK) plus eptifibatide (180/2/180) (dose-finding and dose-confirmation) versus TNK monotherapy (dose-confirmation only). The arrows correspond to the median cTFC for combination therapy (34 frames) and TNK monotherapy (40 frames). As points of reference, 27 frames represents the accepted upper limit of cTFC for Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 in normal individuals, and 40 frames the breakpoint between TIMI flow grades 3 and 2. Pts = patients.
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Figure 4 Rates of successful epicardial (i.e., Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow) and myocardial (i.e., TIMI myocardial perfusion grade 3 [TMPG 3], complete ST-segment resolution [STR]) reperfusion, and the combination of all three at 60-min resolution in all patients (dose-finding and dose-confirmation) who received half-dose tenecteplase and eptifibatide 180/2/180 compared with patients treated with tenecteplase monotherapy (only studied in dose-confirmation). TFG 3 = TIMI flow grade 3.
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