Use of Pexelizumab immediately before and for 24 hours after stent placement or angioplasty for myocardial infarction patients did not have any significant treatment effect compared to placebo.
Acute ST-elevation myocardial infarction ( STEMI ) 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.
Reperfusion with percutaneous transluminal coronary intervention (PCI ) 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 myocardial infarction.
Paul W. Armstrong, 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, 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.
In an accompanying editorial, John W. Eikelboom, and Martin O'Donnell, 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 FDA ( 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 FDA 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."
Source: Journal of American Medical Association, 2007