CLINICAL STUDY
The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study
David P. Faxon, MD*,*,
Raymond J. Gibbons, MD ,
Nicolas A. F. Chronos, MD ,
Paul A. Gurbel, MD ,
Florence Sheehan, MD, PhD|| HALT-MI Investigators
* Los Angeles County Medical Center and the University of Southern California School of Medicine, Los Angeles, California, USA
Mayo Clinic, Rochester, Minnesota, USA
Emory University Hospital, Atlanta, Georgia, USA
Sinai Hospital, Center for Thrombosis Research, Baltimore, Maryland, USA
|| University of Washington, Seattle, Washington, USA
Manuscript received November 17, 2000;
revised manuscript received May 23, 2002,
accepted June 27, 2002.
* Reprint requests and correspondence: Dr. David P. Faxon, Section of Cardiology, The University of Chicago, 5841 S. Maryland Avenue, Room B608, Chicago, Illinois 60637, USA.
dfaxon{at}medicine.bsd.uchicago.edu
OBJECTIVES: The purpose of this study was to determine whether Hu23F2G (LeukoArrest), an antibody to the CD11/CD18 integrin receptors, would reduce infarct size in patients undergoing primary angioplasty for an acute myocardial infarction.
BACKGROUND: Reperfusion injury in acute myocardial infarction has been shown experimentally to be related to neutrophil accumulation. Inhibitors of the CD11/CD18 or CD18 integrin receptors have been shown to reduce infarct size in experimental models.
METHODS: Patients within 6 h of onset of chest pain with ST-segment elevation were randomized to receive either 0.3 mg/kg or 1.0 mg/kg of Hu23F2G or placebo just before angioplasty of occluded arteries (Thrombolysis in Myocardial Infarction TIMI flow grade 0 or 1). The primary end point was infarct size as measured by sestamibi single-photon emission computed tomography (SPECT) scan five to nine days later.
RESULTS: Four-hundred and twenty patients were enrolled and received a placebo or the study drug. The groups did not differ in baseline or angiographic characteristics or angioplasty results. Infarct size was 16%, 17.2% and 16.6%, for placebo, 0.3 mg/kg and 1.0 mg/kg, respectively, of the left ventricle (p = NS). No differences were evident in those patients with anterior myocardial infarction or those presenting within 2 h of onset of chest pain. Corrected TIMI frame count was also not different between groups. Clinical events at 30 days were very low, with a mortality of 0.8%, 1.4% and 3.3%, respectively. The drug was well tolerated, with a slight increase in minor infections in the high dose group.
CONCLUSIONS: The results of this multicenter, double-blind, placebo-controlled, randomized clinical trial demonstrated that an antibody to CD11/CD18 leukocyte integrin receptor did not reduce infarct size in patients who underwent primary angioplasty.
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Abbreviations and Acronyms
| | CK-MB | | creatnine kinase-MB fraction (primarily in cardiac muscle) | | ECG | | electrocardiogram | | MI | | myocardial infarction | | SPECT | | single-photon emission tomography | | TIMI | | Thrombolysis In Myocardial Infarction |
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