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.

Abstract

OBJECTIVE:

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.

• Authors: David P Faxon, Raymond J Gibbons, Nicolas A F Chronos, Paul A Gurbel, Florence Sheehan, HALT-MI Investigators
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 40 Issue 7 Pg. 1199-204 (Oct 02 2002) ISSN: 0735-1097 [Print] United States
• PMID: 12383565 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CD11 Antigens
• CD18 Antigens
• Integrins
• Radiopharmaceuticals
• Technetium Tc 99m Sestamibi
• rovelizumab

Topics

• Angioplasty, Balloon, Coronary
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• CD11 Antigens (immunology)
• CD18 Antigens (immunology)
• Combined Modality Therapy
• Coronary Angiography
• Double-Blind Method
• Electrocardiography
• Female
• Humans
• Integrins (antagonists & inhibitors)
• Male
• Middle Aged
• Myocardial Infarction (diagnosis, immunology, mortality, therapy)
• Proportional Hazards Models
• Radiopharmaceuticals
• Survival Analysis
• Technetium Tc 99m Sestamibi
• Time Factors
• Tomography, Emission-Computed, Single-Photon
• Treatment Outcome