Double-Blind, Randomized Trial of an Anti-CD18 Antibody in Conjunction With Recombinant Tissue Plasminogen Activator for Acute Myocardial Infarction

Abstract

Background-Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the ␤2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. Methods and Results-The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial InfarctionStudy (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at Ն120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (Pϭ0.33). Conclusions-RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points. (Circulation. 2001;

Retroinfusion of NFκB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs

“…9 An additive effect of inhibiting acute, as well as subacute endothelial activation might critically extend the therapeutic strategies for myocardial protection against reperfusion injury, whereas patient outcome has not improved so far when solely acute endothelial activation was inhibited. 15,16 To test the hypothesis that subacute endothelial activation is a significant therapeutic target in the context of postischemic myocardial reperfusion injury, efficient regional transfection of decoy oligonucleotides into ischemic myocardium is essential. The latter is of crucial importance, because the size of the human myocardium exceeds that of a rat about 250-fold, rendering intracoronary arterial injection of decoy ODN unfeasible.…”

Cardiac death by rupture of the right ventricular wall and hemopericardium

“…Therefore the thinness of the wall, the marked necrosis of the terminal area of the artery, the shortage of the collateral circulation, the effect of delamination of the necrotic part by the muscle contraction and the aging of the myocardium, are all implicated as local factors that lead to rupture [26][27][28][29][30][31].…”

Effect of Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Fibrinolysis in Acute Myocardial Infarction

“…Recently, rhuMAb CD 18, an inhibitor of leukocyte adhesion, failed to improve coronary perfusion measured by Thrombolysis In Myocardial Infarction (TIMI) frame count or reduce infarct size in patients with acute MI. 19 One possibility regarding the treatment failure in humans is that inhibition of one element of the inflammatory cascade is ineffective.…”