Medication Does Not Appear to Offer Benefit for Certain Heart Attack Patients Undergoing Angioplasty or Stent Procedure

CHICAGO, Jan.2, 2006—Use of the drug pexelizumab immediately before and for 24 hours after stent placement or angioplasty for certain heart attack patients did not have any significant treatment effect compared to placebo, according to a study in the January 3 issue of JAMA. The medication had shown promise in preliminary studies.

Acute ST-elevation myocardial infarction (STEMI; a certain pattern on an electrocardiogram following a heart attack) is a major public health problem, not only in western countries but increasingly in developing countries. In the United States, there are estimated to be more than half a million STEMI events annually, which has spurred efforts to improve treatments, according to background information in the article. Reperfusion (restoring blood flow) with percutaneous transluminal coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries) is highly effective at improving outcomes in patients with acute STEMI, especially if delivered promptly in an expert facility. However, in patients without prompt reestablishment of adequate coronary blood flow, risk of death remains high, indicating the need for new treatments, including drugs intended to reduce the inflammation associated with a heart attack.

Paul W. Armstrong, M.D., of the University of Alberta, Edmonton, Canada, and investigators with the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI) trial, evaluated the effectiveness of the intravenous administration of the medication pexelizumab in conjunction with primary PCI in lowering the risk of death from STEMI. The double-blind, placebo-controlled, phase 3 study include 5,745 patients, of whom 2,885 were randomly assigned to receive placebo and 2,860 to receive pexelizumab, prior to PCI followed by infusion over the subsequent 24 hours. The patients were treated at 296 hospitals in 17 countries from July 2004 to May 2006.

The researchers found that there was no difference in the rate of death at 30 days between placebo and pexelizumab treated patients, i.e., each experiencing a low death rate of 3.92 percent and 4.06 percent, respectively. The 30-day composite end point of death, cardiac shock, or heart failure was also similar between treatment groups (9.19 percent for placebo and 8.99 percent with pexelizumab). At 90 days death remained low and similar in both treatment groups, i.e., 4.51 percent and 4.93 percent for placebo and pexelizumab, respectively. The composite end point of death, shock, or heart failure was also similar at day 90.

“It remains unclear whether other myocardial protection strategies including anti-inflammatory, antiapoptotic [prevention of cell death], or metabolic manipulation might be successful. Whereas a proinflammatory state relates to worse outcomes, and we have previously shown that it can be modified by pexelizumab the extent to which inflammation is caused by vs. contributes to myocardial damage is unknown. Timing of administration of therapies and targeting high-risk patients most likely to benefit are likely important variables in the modulation of inflammation in the clinical setting. The lack of benefit of pexelizumab in APEX underscores the challenge of translating promising experimental treatments for myocardial protection to the clinic,” the authors write.
(JAMA. 2007;297:43-51. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: This study was jointly funded by Procter & Gamble Pharmaceuticals and Alexion Pharmaceuticals. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

EDITORIAL: PEXELIZUMAB DOES NOT ‘COMPLEMENT’ PCI IN PATIENTS WITH STEMI

In an accompanying editorial, John W. Eikelboom, M.B.B.S., and Martin O’Donnell, M.B., of McMaster University, Hamilton, Ontario, comment on the findings concerning pexelizumab.

“What are the implications of the APEX AMI trial results for clinical practice and future research? Despite the promising results of the early pexelizumab trials, it seems unlikely that this drug provides any major benefit in preventing reperfusion injury when it is used as an adjunct to primary PCI in patients with STEMI. Furthermore, commercial realities make it unlikely that additional trials will be conducted with this drug in the future. The revised statistical analysis plan for the APEX AMI trial, developed in consultation with the U.S. Food and Drug Administration, details plans for a meta-analysis of all 6 completed pexelizumab studies. Even if the meta-analysis reports a significant benefit of pexelizumab, it is unclear whether the Food and Drug Administration will approve the drug or require an additional study. Despite the disappointing results of the pexelizumab trials, the central hypothesis, that modulating inflammatory mediators may improve clinical outcomes by reducing reperfusion injury, remains worthy of further study.”
(JAMA. 2007;297:91-92. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Dr. Eikelboom is the recipient of a Tier II Canada Research Chair in Cardiovascular Medicine from the Canadian Institutes for Health Research. Dr. O’Donnell is the recipient of a Mentor-Mentee Clinical Trials Award from the Canadian Institutes for Health Research and holds the William Walsh Research Chair in Internal Medicine. Financial disclosures: none reported.

For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations@jama-archives.org .

Posted: January 2007

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