Pexelizumab for Acute ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention (original) (raw)

Abstract

CUTE ST-ELEVATION MYOCARdial infarction (STEMI) constitutes a major public health problem, not only in western countries but increasingly in developing countries. 1 In the United States, there are estimated to be more than half a million STEMI events annually and these have provided strong impetus for efforts to improve both the process whereby care is delivered and the treatment elements administered. 2 Although reperfusion with primary percutaneous transluminal coronary intervention (PCI) is highly effective, especially if delivered promptly in an expert facility, it is now appreciated that not all PCIs adequately restore myocardial or tissue perfusion. 3 Reperfusion achieved through primary PCI and coronary stenting may be associated with distal coronary embolization, endothelial dysfunction, and impaired ventricular function. 4 A concomitant inflammatory reaction, participating in the accompanying reperfusion injury may mediate apoptosis in the periinfarction area and unfavorable left ventricular remodeling. 5 Poor tissue perfusion and the intensity of the inflammatory response are related to subsequent mortality. 4,6 Complement is known to be both activated and a potential mediator of these processes, and activation of the terminal components of the complement cascade leads to cleavage of the C5 component: this in turn results in formation of both C5a, a potent anaphylatoxin and proinflammatory substance, and C5b-9 or the membrane attack complex (MAC), which causes vesiculation of platelets and endothelial cells, formation of prothrombotic microparticles, and activation of leu-kocytes and endothelial cells. Hence, inhibition of C5 constitutes an attractive therapeutic target. 7 For editorial comment see p 91.

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References (42)

  1. and Executive, and Publication Commit- tee: Paul W. Armstrong, MD, Department of Medi- cine, University of Alberta, Edmonton, Alberta (Chair);
  2. Christopher B. Granger, MD, Duke University Medi- cal Centre, Durham, NC (Vice-Chair);
  3. Peter X. Adams, MD, Alexion Pharmaceuticals, Cheshire, Conn;
  4. Christian Hamm, MD, Kerckhoff Heart Centre, Bad Nauheim, Germany; David Holmes, Jr, MD, Mayo Clinic, Rochester, Minn; William W. O'Neill, MD, Uni- versity of Miami, Miami, Fla; Thomas G. Todaro, MD, JD, Procter & Gamble Pharmaceuticals, Cincinnati, Ohio; Alec Vahanian, MD, Hospital Bichat, Paris, France; Frans Van de Werf, MD, PhD, Department of Cardiology, University Hospital Gathuisberg, Leu- ven, Belgium. Authors and Steering Committee Members: Hussein Al-Khalidi, PhD, Procter & Gamble Pharmaceuticals, Cincinnati, Ohio; Diego Ardissino, MD, Maggiore Hos- pital of Parma, University of Parma, Parma, Italy; Phil Aylward, MD, PhD, FRACP, Flinders Medical Centre, Bedford Park, Australia; Amadeo Betriu, MD, Clinic Barcelona, Universitat de Barcelona, Barcelona, Spain;
  5. Judith Hochman, MD, New York University School of Medicine, New York; Kurt Huber, MD, University of Vienna, Vienna, Austria; Stefan James, MD, PhD, Upp- sala University Hospital, Uppsala, Sweden; Kerry Lee, PhD, Duke Clinical Research Institute, Durham, NC;
  6. Kenneth W. Mahaffey, MD, Duke Clinical Research Institute, Durham, NC; David Moliterno, MD, Divi- sion of Cardiovascular Medicine, University of Ken- tucky, Lexington; Gilles Montalescot, MD, PhD, De- partment of Cardiology, Ho ˆpital la Pitie ´-Salpe ´trière Institut du Coeur, Paris, France; Franz-Josef Neumann, MD, PhD, Heart Centre Bad Krozingen, Bad Krozin- gen, Germany; Torsten Toftegaard Nielsen, MD, PhD, Skejby University Hospital, Aarhus, Denmark; Matthias Pfisterer, MD, Department of Internal Medicine, Basel University Hospital, Basel, Switzerland; Witold Ruz ´yllo, MD, National Institute of Cardiology, Warsaw, Po- land; Ricardo Seabra-Gomes, MD, Santa Cruz Hos- pital, Carnaxide, Portugal; Pierre Theroux, MD, Mon- treal Heart Institute, Montreal, Quebec, Canada; Arnoud van 't Hof, MD, Department of Cardiology, Hospital De Weezenlanden, Zwolle, the Nether- lands; W. Douglas Weaver, MD, Division of Cardiol- ogy, Henry Ford Hospital, Detroit, Mich; Harvey White, MD, DSc, Auckland City Hospital, Auckland, New Zealand; Petr Widimsky, MD, PhD, Kralovske Vinohrady University Hospital, Prague, Czech Republic. Financial Disclosures: Drs Armstrong, Granger, and Van de Werf received research grants from the trial sponsors. Members of the Steering Committee re- ceived honoraria for their participation. K. Mahaffey, has received research grants and consultant fees from Alexion Pharmaceuticals. Author Contributions: Drs Armstrong (chair) and Granger (vice-chair) had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Armstrong, Granger, Adams, Hamm, Holmes, O'Neill, Todaro, Vahanian, Van de Werf. Acquisition of data: Armstrong, Granger, Adams, Todaro, and the APEX Steering/Executive Commit- tees. Analysis and interpretation of data: Adams, Al-Khalidi, Ardissino, Armstrong, Aylward, Granger, Hamm, Hochman, Holmes, James, Lee, Mahaffey, Moliterno, Montalescot, Neumann, Seabra-Gomes, Theroux, Todaro, Vahanian, Van de Werf, Weaver, White, Widmsky. Drafting of the manuscript: Armstrong, Granger, Al-Khalidi. Critical revision of the manuscript for important in- tellectual content: APEX Steering and Executive Com- mittees, and Mahaffey. Statistical analysis: Al-Khalidi, Lee. Obtained funding: Armstrong, Granger, Todaro, Adams.
  7. Administrative, technical, or material support: Armstrong, Granger, and APEX Executive Committee. Study supervision: Ardissino, Armstrong, Aylward, Holmes, Moliterno, Montalescot, Neumann, Nielsen, O'Neill, Pfisterer, Ruz ´yllo, Todaro, Vahanian, Van de Werf. Global Operational Leadership: L. Berdan, R. Char- bonneau, T. Rorick.
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  14. A. Amkieh (1), H. V. Anderson (1), J. Anderson (3), B. Armstrong (16), W. Asfour (1), T. Ayres (5), M. Azrin (5), Z. Baber (30), L. Barr (18), G. Barsness
  15. J. Batty (1), M. Bikkina (8), J. Blankenship (62), D. Campbell (7), P. Caples (14), T. Carlson (9), J. Cham- bers (4), H. Chandna (15), B. Cheek (16), J. Cheirif (2), A. Chu (10), H. Colfer (11), B. Crenshaw (36), S. David (12), A. DeFranco (2), J. Dehoya (3), J. Diez (11), G. Eaton (1), E. Eichhorn (3), M. El Shahawy (8), T. Farah (9), W. Felten (9), D. Fortuin (14), M. Foster (10), D. S. Gantt (12), J. Gard (4), M. Ghali (39), R. Glaser (2), M. Greenberg (8), J. Griffin (26), G. Ha- novich (1), N. Hassinger (17), S. Heifetz (27), T. Henry
  16. J. Hermiller (12), J. Hernandez (8), R. Hodson (7), M. Imburgia (3), B. Iteld (7), Z. Jafar (7), A. Jain (7), N. Jamal (4), G. Kang (5), R. Karlsberg (9), S. Khanal (35), S. Khoury (11), J. Kieval (15), R. Kipperman (8), B. Kluck (1), D. Kong (59), E. Kosinski (12), M. Kozak
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