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CLINICAL RESEARCH: COMBINED GLYCOPROTEIN IIB/IIIA INHIBITORS AND FIBRINOLYTICS

Improved speed and stability of st-segment recovery with reduced-dose tenecteplase and eptifibatide compared with full-dose tenecteplase for acute st-segment elevation myocardial infarction

Matthew T. Roe, MD, MHS, FACC^*,*, Cynthia L. Green, PhD^*, Robert P. Giugliano, MD, SM, FACC, C. Michael Gibson, MD, FACC, Kenneth Baran, MD, Mark Greenberg, MD, Sebastian T. Palmeri, MD^||, Suzanne Crater, ANP-C^*, Kathleen Trollinger, RN^*, Karen Hannan, MS^*, Robert A. Harrington, MD, FACC^*, Mitchell W. Krucoff, MD, FACC^* INTEGRITI Investigators

^* Duke Clinical Research Institute and Division of Cardiology, Duke Medical Center, Durham, North Carolina, USA
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA
John Nasseff Heart Hospital, St. Paul, Minnesota, USA
Montefiore Medical Center, New York, New York, USA
^|| Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

Manuscript received June 11, 2003; revised manuscript received August 8, 2003, accepted September 15, 2003.

^* Reprint requests and correspondence: Dr. Matthew T. Roe, Duke Clinical Research Institute, P.O. Box 17969, Durham, North Carolina 27715, USA.
roe00001{at}mc.duke.edu

OBJECTIVES: This sub-study of the Integrilin and Tenecteplase in Acute Myocardial Infarction (INTEGRITI) trial evaluated of the impact of combination reperfusion therapy with reduced-dose tenecteplase plus eptifibatide on continuous ST-segment recovery and angiographic results.

BACKGROUND: Combination therapy with reduced-dose fibrinolytics and glycoprotein IIb/IIIa inhibitors for ST-segment elevation myocardial infarction improves biomarkers of reperfusion success but has not reduced mortality when compared with full-dose fibrinolytics.

METHODS: We evaluated 140 patients enrolled in the INTEGRITI trial with 24-h continuous 12-lead ST-segment monitoring and angiography at 60 min. The dose-combination regimen of 50% of standard-dose tenecteplase (0.27 µg/kg) plus high-dose eptifibatide (2 boluses of 180 µg/kg separated by 10 min, 2.0 µg/kg/min infusion) was compared with full-dose tenecteplase (0.53 µg/kg).

RESULTS: The dose-confirmation regimen of reduced-dose tenecteplase plus high-dose eptifibatide was associated with a faster median time to stable ST-segment recovery (55 vs. 98 min, p = 0.06), improved stable ST-segment recovery by 2 h (89.6% vs. 67.7%, p = 0.02), and less recurrent ischemia (34.0% vs. 57.1%, p = 0.05) when compared with full-dose tenecteplase. Continuously updated ST-segment recovery analyses demonstrated a modest trend toward greater ST-segment recovery at 30 min (57.7% vs. 40.6%, p = 0.13) and 60 min (82.7% vs. 65.6%, p = 0.08) with this regimen. These findings correlated with improved angiographic results at 60 min.

CONCLUSIONS: Combination therapy with reduced-dose tenecteplase and eptifibatide leads to faster, more stable ST-segment recovery and improved angiographic flow patterns, compared with full-dose tenecteplase. These findings question the relationship between biomarkers of reperfusion success and clinical outcomes.

Abbreviations and Acronyms   CTFC = corrected TIMI frame count   ECG = electrocardiogram/electrocardiographic   GP = glycoprotein   IMCL = Ischemia Monitoring Core Laboratory   INTEGRITI = Integrilin and Tenecteplase in Acute Myocardial Infarction trial   IRA = infarct-related artery   PCI = percutaneous coronary intervention   STEMI = ST-segment elevation myocardial infarction   TIMI = Thrombolysis In Myocardial Infarction   TMPG = TIMI myocardial perfusion grade

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