Although preliminary studies had been positive, the large-scale APEX AMI Trial found that pexelizumab in the peri-procedural period for percutaneous coronary intervention had no significant treatment effect compared with placebo, according to an article in the January 3 issue of the Journal of the American Medical Association.

The drug was given immediately before and for 24 hours after stent placement or angioplasty to patients with acute ST-elevation myocardial infarction. Drug use was intended to reduce inflammation associated with acute myocardial infarctions and reperfusion procedures.

Paul W. Armstrong, MD, 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 intravenous pexelizumab in conjunction with a primary procedure in reducing risk of death from ST-elevation infarction.

The double-blind, placebo-controlled, phase III study include 5,745 patients, with 2,885 randomized to placebo and 2,860 to pexelizumab prior to their procedures followed by infusion over the next 24 hours. The patients were treated at 296 hospitals in 17 countries from July 2004 to May 2006.

There was no difference in mortality rate at 30 days between placebo and pexelizumab (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 (4.51 percent and 4.93 percent for placebo and pexelizumab, respectively), as was the composite end point of death, shock, or heart failure.

"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 versus 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 wrote.

In an accompanying editorial, John W. Eikelboom, MBBS, and Martin O'Donnell, MB, of McMaster University, Hamilton, Ontario, commented: "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…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."