 |
|
Pexelizumab for Acute ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention
A Randomized Controlled Trial
The APEX AMI Investigators*
JAMA. 2007;297:43-51.
Context Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents.
Objective To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI.
Design, Setting, and Patients This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006.
Interventions Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset.
Main Outcome Measures The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90.
Results No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91).
Conclusion In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.
Trial Registration clinicaltrials.gov Identifier: NCT00091637
*APEX AMI Investigators: (number in parentheses indicates patients enrolled): Australia (479): N. Bett (5), D. Brieger (6), D. Chew (49), R. Dick (12), A. Farshid (14), P. Garrahy (6), B. Gunalingham, (8), R. Hendriks (14), J. Horowitz (84), N. Jepson (5), J. Lefkovits (15), S. Lo (7), I. Meredith (15), G. Nelson (32), G. New (8), A. Prasan (40), J. Rankin (98), P. Thompson (17), S. Worthley (41), R. Yadav (3). Austria (41): K. Huber (17), G. Maurer (3), P. Siostrzonek (21). Belgium (87): J. Boland (30), C. Covens (12), W. Desmet (21), K. Dujardin (9), M. Vrolix (15). Canada (335): C. Buller (19), P. Klinke (10), C. Lazzam (26), S. Lutchmedial (16), M. Madan (14), M. Natarajan (20), F. Reeves (10), J. Rodes Cabau (65), B. Rose (6), E. Schampaert (10), P. Theroux (58), M. Traboulsi (32), J. Webb (8), R. Welsh (4), R. Zimmerman (37). Czech Republic (967): M. Aschermann (72), M. Branny (42), T. Budesinsky (38), P. Cervinka (33), H. Frantisek (120), T. Frantisek (60), L. Groch (120), P. Kala (42), M. Ritcher (111), R. Rokyta (45), J. St'asek (55), R. Stipal (35), I. Varvarovsky (42), D. Zamanek (32), M. Zelizko (120). Denmark (173) : T. Toftegaard Nielsen (45), K. Rasmussen (48), P. RiisHansen (71), P. Thayssen (9). France (88): P. Beaufils (9), P. Geslin (8), Y. Gottwalles (18), H. Lebreton (6), H. LeMarec (6), G. Montalescot (16), G. Roul (3), P. G. Steg (6), C.Tronc (16). Germany (398): H. J. Berger (19), M. Borggrefe (8), J. Brachmann (39), P. Braun (23), M. Buerke (9), H. R. Figulla (13), H. Guelker (27), G. Hasenfuss (8), T. Heitzer (13), H. Heuer (5), E. Hoffman (1), S. Hoffmann (11), K. H. Kuck (3), F. J. Neumann (35), J. Neuzner (24), M. Rau (23), G. Richardt (4), H. Schunkert (64), R. Stern (20), W. von Schedit (12), P. C. Werner (15), R. Zahn (22). Italy (351): G. Binetti (56), E. Bramucci (102), G. Carosio (4), A. Manari (34), A. Marzocchi (9), M. Medda (7), G. Piovaccari (70), A. Politi (1), L. Vignali (26), R. Violini, (15), M. Zanchetta (5), R. Zanini (22). the Netherlands (255): K. Marques (3), H. Otto Peels (28), T. Slagboom (39), P. C. Smits (39), H. Suryapranata (119), M. .J. Suttorp (21), M. VanDerEnt (6). New Zealand (79): I. Crozier (22), G. Devlin (25), S. Harding (7), H. White (19), G. Wilkins (6). Poland (370): M. Krzeminska-Pakula (65), K. Loboz-Grudzien (18), W. Ru yllo (87), W. Tracz (80), M. Trusz-Gluza (120). Portugal (148): M. Almeida (26), J. Correiada Cunha (3), P. Farto Abreu (13), L. Mourão (29), H. Pereira (60), L. Providencia (15), R. Vascoda Gama (2). Spain (115): A. Bertriu (12), C. Cuellas (4), E. Esplugas (14), E. Garcia Fernandez (15), X. Goicolea (19), J. M. Hernandez, (7), C. Macaya (13), V. Mainar (23), A. Sanchez (8). Sweden (56): P. Erikksson (4), S. James (8), G. Olivercrona (41), C. M. Pripp (3). Switzerland (52): E. Camenzind (12), M. Pfisterer (15), M. Pieper (15), H. Rickli (10). United States (1751) : R. Acheatel (60), A. Ahmad (1), A. Albirini (43), R. Allen (4), 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 (31), J. Batty (1), M. Bikkina (8), J. Blankenship (62), D. Campbell (7), P. Caples (14), T. Carlson (9), J. Chambers (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. Hanovich (1), N. Hassinger (17), S. Heifetz (27), T. Henry (1), 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 (4), H. Kozman (12), P. Kraft (15), A. Labroo (2), P. Lai (6), N. Lakkis (5), G. Lane (4), B. Laretta (7), D. Lee (4), M. Leesar (8), J. Leggett (27), M. Levine (1), S. Lieberman (7), M. Lim (14), J. Luber (7), V. Marques (15), K. Marzo (12), J. McGarvey Jr (6), G. McKendall (44), B. McLellan (10), M. Meengs (3), D. Mego (7), A. Mehra (13), J. A. Messenger (2), J. O. Messenger, (8), M. Midei (141), M. Miller (13), D. Moliterno (33), K. Momah (2), M. Mowdy (2), A. Nahhas (1), J. Navas (2), A. Niederman (5), T. Nygaard (85), W. O'Neill (20), K. Patel (10), S. Pfau (1), V. Pompili (2), D. Purdy (32), B. Reddy (29), A. Rees (9), J. Reiner (3), A. Riba (7), E. Rivera (3), D. Roberts (1), A. Rosenblatt (3), W. Rowe (5), S. Rowley (6), D. Rubin (4), K. Saeian (1), F. Saltiel (1), S. Sample (3), B. Sanchez (1), I. Sarembock (18), J. Saucedo (9), T. Schreiber (3), R. Shah (5), M. Singh (21), J. Slater (5), R. Small (14), C. Staniloae (6), P. S. Sundram (3), L. Swenson (22), G. Symkoviak (4), K. Tam (7), A. Taussig (2), J. Thatcher (1), P. Tolerico (7), J. Trippi (2), S. Turk (8), K. Van Osdol (23), R. Vicari (2), A. Virmani (12), M. Warner (13), R. Webel (11), J. Wertheimer (1), G. Williams (4), J. Williams (29), M. Winniford (1), D. Wohns (4), DX-M Zhao (3), Total (5745).
RELATED LETTERS
Pexelizumab and the APEX AMI Trial
Paul W. Armstrong and Christopher B. Granger
JAMA. 2007;297(17):1881.
EXTRACT
| FULL TEXT
Pexelizumab and the APEX AMI Trial—Reply
John W. Eikelboom and Martin O’Donnell
JAMA. 2007;297(17):1881-1882.
EXTRACT
| FULL TEXT
RELATED ARTICLE
Pexelizumab Does Not "Complement" Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction
John W. Eikelboom and Martin O’Donnell
JAMA. 2007;297(1):91-92.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
The year in interventional cardiology.
Dixon et al.
J Am Coll Cardiol 2008;51:2355-2369.
FULL TEXT
Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction
Kasama et al.
Eur Heart J 2008;29:1485-1494.
ABSTRACT
| FULL TEXT
Bivalirudin during Primary PCI in Acute Myocardial Infarction
Stone et al.
NEJM 2008;358:2218-2230.
ABSTRACT
| FULL TEXT
Reperfusion after primary angioplasty for ST-elevation myocardial infarction: predictors of success and relationship to clinical outcomes in the APEX-AMI Angiographic Study
Brener et al.
Eur Heart J 2008;29:1127-1135.
ABSTRACT
| FULL TEXT
Cardiogenic Shock: Current Concepts and Improving Outcomes
Reynolds and Hochman
Circulation 2008;117:686-697.
FULL TEXT
Failure of investigator adherence to electrocardiographic entry criteria is frequent and influences clinical outcomes: lessons from APEX-AMI
Tjandrawidjaja et al.
Eur Heart J 2007;28:2850-2857.
ABSTRACT
| FULL TEXT
Physiologic Straws in the Wind: In Which Direction Do They Bend?
Lewanczuk and Armstrong
J Am Coll Cardiol 2007;50:2059-2060.
FULL TEXT
The Calm After the Storm: Long-Term Survival After Cardiogenic Shock
Hochman and Apolito
J Am Coll Cardiol 2007;50:1759-1760.
FULL TEXT
Myocardial Reperfusion Injury
Yellon and Hausenloy
NEJM 2007;357:1121-1135.
FULL TEXT
The Search for Myocardial Protection: Is There Still Hope?
Granger and Patel
J Am Coll Cardiol 2007;50:406-408.
FULL TEXT
The Year in Interventional Cardiology
Dixon et al.
J Am Coll Cardiol 2007;50:270-285.
FULL TEXT
Translational research: Is there a future?
Verrier
J. Thorac. Cardiovasc. Surg. 2007;133:1409-1411.
FULL TEXT
Reperfusion injury in humans: A review of clinical trials on reperfusion injury inhibitory strategies
Dirksen et al.
Cardiovasc Res 2007;74:343-355.
ABSTRACT
| FULL TEXT
Pexelizumab and the APEX AMI Trial
Armstrong and Granger
JAMA 2007;297:1881-1881.
FULL TEXT
Pexelizumab and the APEX AMI Trial--Reply
Eikelboom and O'Donnell
JAMA 2007;297:1881-1882.
FULL TEXT
JournalScan
Lindsay
Heart 2007;93:645-647.
FULL TEXT
Effect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock: The TRIUMPH Randomized Controlled Trial
The TRIUMPH Investigators
JAMA 2007;297:1657-1666.
ABSTRACT
| FULL TEXT
Pexelizumab fails to improve outcomes after heart attack
BMJ 2007;334:66-66.
FULL TEXT
No Benefit of Complement Inhibition in STEMI
Journal Watch Cardiology 2007;2007:1-1.
FULL TEXT
Pexelizumab Does Not "Complement" Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction
Eikelboom and O'Donnell
JAMA 2007;297:91-92.
FULL TEXT
|
