Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial.

Abstract

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.

• Authors: APEX AMI Investigators, Paul W Armstrong, Christopher B Granger, Peter X Adams, Christian Hamm, David Holmes Jr, William W O'Neill, Thomas G Todaro, Alec Vahanian, Frans Van de Werf
• Journal: JAMA (JAMA) Vol. 297 Issue 1 Pg. 43-51 (Jan 03 2007) ISSN: 1538-3598 [Electronic] United States
• PMID: 17200474 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Single-Chain Antibodies
• pexelizumab

Topics

• Aged
• Angioplasty, Balloon, Coronary
• Anti-Inflammatory Agents (administration & dosage, therapeutic use)
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Double-Blind Method
• Female
• Heart Failure (epidemiology)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Myocardial Infarction (mortality, therapy)
• Prospective Studies
• Shock, Cardiogenic (epidemiology)
• Single-Chain Antibodies
• Survival Analysis