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Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction.

Publication ,  Journal Article
Armstrong, PW; Mahaffey, KW; Chang, W-C; Weaver, WD; Hochman, JS; Theroux, P; Rollins, S; Todaro, TG; Granger, CB; COMMA Investigators,
Published in: Am Heart J
April 2006

BACKGROUND: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizumab despite no reduction in the primary end point of myocardial infarction (MI) size. We examined whether the mortality benefit was related to established modulators of clinical benefit such as baseline demographics, time to treatment from symptom onset, myocardial perfusion post-percutaneous coronary intervention (PCI), and extent of ST resolution. METHODS AND RESULTS: Eight hundred fourteen patients were randomized into 3 groups; (1) placebo, (2) pexelizumab bolus 2.0 mg/kg and placebo infusion for 20 hours, and (3) pexelizumab bolus 2.0 and 0.05 mg/kg per hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine kinase (CK), and CK-MB measurements taken sequentially to define CK-MB area under the curve (AUC) and sequential ECG's defined ST resolution and QRS infarct size. Whereas mortality for both placebo and bolus pexelizumab groups rose during later time after presentation, it remained low and did not change appreciably during the 6-hour randomization window when patients received pexelizumab bolus infusion. Amplification of the mortality benefit was evident in patients with the highest quartile of hemodynamic compromise, that is, heart rate > or = 90 beat/min and systolic blood pressure < or = 118 mm Hg (3.2% vs 11.3% P = .004). A significant interaction between treatment assignment and hemodynamic status (P = .013) existed after adjusting for age, race, and MI location. Clinical benefit was not related to infarct size, extent of ST elevation, or evidence of angiographic or electrocardiographic reperfusion. CONCLUSIONS: These data raise the possibility that the clinical benefit of pexelizumab is mediated through novel pathways such as reduction in apoptosis or other mechanisms.

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Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

April 2006

Volume

151

Issue

4

Start / End Page

787 / 790

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Analysis
  • Single-Chain Antibodies
  • Randomized Controlled Trials as Topic
  • Myocardial Infarction
  • Microcirculation
  • Logistic Models
  • Immunologic Factors
  • Humans
  • Hemodynamics
 

Citation

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Armstrong, P. W., Mahaffey, K. W., Chang, W.-C., Weaver, W. D., Hochman, J. S., Theroux, P., … COMMA Investigators, . (2006). Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction. Am Heart J, 151(4), 787–790. https://doi.org/10.1016/j.ahj.2005.06.008
Armstrong, Paul W., Kenneth W. Mahaffey, Wei-Ching Chang, W Douglas Weaver, Judith S. Hochman, Pierre Theroux, Scott Rollins, Thomas G. Todaro, Christopher B. Granger, and Christopher B. COMMA Investigators. “Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction.Am Heart J 151, no. 4 (April 2006): 787–90. https://doi.org/10.1016/j.ahj.2005.06.008.
Armstrong PW, Mahaffey KW, Chang W-C, Weaver WD, Hochman JS, Theroux P, et al. Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction. Am Heart J. 2006 Apr;151(4):787–90.
Armstrong, Paul W., et al. “Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction.Am Heart J, vol. 151, no. 4, Apr. 2006, pp. 787–90. Pubmed, doi:10.1016/j.ahj.2005.06.008.
Armstrong PW, Mahaffey KW, Chang W-C, Weaver WD, Hochman JS, Theroux P, Rollins S, Todaro TG, Granger CB, COMMA Investigators. Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction. Am Heart J. 2006 Apr;151(4):787–790.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

April 2006

Volume

151

Issue

4

Start / End Page

787 / 790

Location

United States

Related Subject Headings

  • Time Factors
  • Survival Analysis
  • Single-Chain Antibodies
  • Randomized Controlled Trials as Topic
  • Myocardial Infarction
  • Microcirculation
  • Logistic Models
  • Immunologic Factors
  • Humans
  • Hemodynamics