Pexelizumab fails to inhibit assembly of the terminal complement complex in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Insight from a substudy of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial

American Heart Journal

Volumn 164, Issue 1, 2012, Pages 43-51

  Martel, Catherine ^a   Granger, Christopher B ^b   Ghitescu, Marta ^a   Stebbins, Amanda ^b   Fortier, Annik ^a   Armstrong, Paul W ^c   Bonnefoy, Arnaud ^a,d   Theroux, Pierre ^a  

^a MONTREAL HEART INSTITUTE   (Canada)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

^c UNIVERSITY OF ALBERTA   (Canada)

^d U743 INSERM   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; C REACTIVE PROTEIN; COMPLEMENT COMPONENT C5A; COMPLEMENT MEMBRANE ATTACK COMPLEX; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 6; PEXELIZUMAB; PLACEBO; RANTES;

ADULT; AGED; APOPTOSIS; ARTICLE; CELL CULTURE; CLINICAL ASSESSMENT; COMPLEMENT ACTIVATION; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; INFLAMMATION; MAJOR CLINICAL STUDY; MALE; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; UMBILICAL VEIN ENDOTHELIAL CELL;

AGED; ANGIOPLASTY, BALLOON, CORONARY; ANTIBODIES, MONOCLONAL, HUMANIZED; COMPLEMENT MEMBRANE ATTACK COMPLEX; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; MYOCARDIAL INFARCTION; PROSPECTIVE STUDIES; SINGLE-CHAIN ANTIBODIES; TREATMENT FAILURE;

EID: 84863723951     PISSN: 00028703     EISSN: 10976744     Source Type: Journal    
DOI: 10.1016/j.ahj.2012.04.007     Document Type: Article

References (22)

1. Diepenhorst GM, van Gulik TM, Hack CE. Complement-mediated ischemia reperfusion injury: lessons learned from animal and clinical studies. Ann Surg 2009;249:889-99.
2. Thomas TC, Rollins SA, Rother RP, et al. Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol 1996;33:1389-401. (Pubitemid 27196373)
3. Fitch JCK, Rollins S, Matis L, et al. Pharmacology and biological efficacy of a recombinant, humanized, single-chain antibody C5 complement inhibitor in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. Circulation 1999;100:2499-506. (Pubitemid 30005113)
4. Mahaffey KW, Van de Werf F, Shernan SK, et al. Effect of pexelizumab on mortality in patients with acute myocardial infarction or undergoing coronary artery bypass surgery: a systematic overview. Am Heart J 2006;152:291-6. (Pubitemid 44093412)
5. The APEX AMI Investigators. Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial. JAMA 2007;297:43-51.
6. Testa L, Van Gaal WJ, Bhindi R, et al. Pexelizumab in ischemic heart disease: a systematic review and meta-analysis on 15,196 patients. J Thorac Cardiovasc Surg 2008;136:884-93.
7. Smith PK, Shernan SK, Chen JC, et al, PRIMO-CABG II Investigators. Effects of C5 complement inhibitor pexelizumab on outcome in high-risk coronary artery bypass grafting: combined results from the PRIMO-CABG I and II trials. J Thorac Cardiovasc Surg 2011;142:89-98.
8. Gerard C, Hugh TE. Identification of classical anaphylatoxin as the des-Arg form of the C5a molecule: evidence of a modulator role for the oligosaccharide unit in human des-Arg74-C5a. Proc Natl Acad Sci U S A 1981;78:1833-7. (Pubitemid 11114271)
9. Nicoletti I, Migliorati G, Pagliacci MC, et al. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 1991;139:271-9.
10. Nijmeijer R, Krijnen PA, Assink J, et al. C-reactive protein and complement depositions in human infarcted myocardium are more extensive in patients with reinfarction or upon treatment with reperfusion. Eur J Clin Invest 2004;34:803-10. (Pubitemid 39657927)
11. Haahr-Pedersen S, Bjerre M, Flyvbjerg A, et al. Level of complement activity predicts cardiac dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention. J Invasive Cardiol 2009;21:13-9.
12. Trendelenburg M, Theroux P, Stebbins A, et al. Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J 2010;31:1181-7.
13. Sprong T, Brandtzaeg P, Fung M, et al. Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis. Blood 2003;102:3702-10. (Pubitemid 37409391)
14. Huber-Lang M, Sarma JV, et al. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 2006;12:682-7. (Pubitemid 43865238)
15. Scholz W, McClurg MR, Cardenas GJ, et al. C5a-mediated release of interleukin 6 by human monocytes. Clin Immunol Immunopathol 1990;57:297-307. (Pubitemid 20368042)
16. Hashimoto M, Hirota K, Yoshitomi H, et al. Complement drives Th17 cell differentiation and triggers autoimmune arthritis. J Exp Med 2010;207:1135-43.
17. Theroux P, Armstrong PW, Mahaffey KW, et al. Prognostic significance of blood markers of inflammation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty and effects of pexelizumab, a C5 inhibitor: a substudy of the COMMA trial. Eur Heart J 2005;26:1964-70. (Pubitemid 41435718)
18. Ezekowitz JA, Théroux P, Chang W, et al. NT-proBNP and the timing, extent and mortality in ST-elevation myocardial infarction. Can J Cardiol 2006;22:393-7. (Pubitemid 43834011)
19. Monsinjon T, Gasque P, Chan P, et al. Regulation by complement C3a and C5a anaphylatoxins of cytokine production in human umbilical vein endothelial cells. FASEB J 2003;17:1003-14. (Pubitemid 36681518)
20. Vakeva AP, Agah A, Rollins SA, et al. Myocardial infarction and apoptosis after myocardial ischemia and reperfusion: role of the terminal complement components and inhibition by anti-C5 therapy. Circulation 1998;22:2259-67. (Pubitemid 28265388)
21. Nohé B, Kiefer RT, Ploppa A, et al. The effects of fresh frozen plasma on neutrophil-endothelial interactions. Anesth Analg 2003:216-21. (Pubitemid 36736564)
22. Bombeli T, Karsan A, Tait JF, et al. Apoptotic vascular endothelial cells become procoagulant. Blood 1997;89:2429-42. (Pubitemid 27143290)