Complement Suppression Drug Does Not Prevent Cognitive Decline After CABG

Treatment with pexelizumab, a monoclonal antibody against the C5 complement component, does not prevent the overall drop in cognition that can occur after coronary artery bypass grafting (CABG), new research shows. However, the drug may help prevent dysfunction in the visuo-spatial domain.

The cognitive decline that occurs after CABG is thought to arise primarily from cerebral embolization, although inflammatory processes following the initial insult may dramatically alter the extent of injury, Dr. Joseph P. Mathew, from Duke University Medical Center in Durham, North Carolina, and colleagues note. Because such processes typically involve complement activation, treatments that block complement components could potentially have a beneficial effect on cognition.

To investigate, Dr. Mathew and colleagues assessed the cognitive outcomes of 914 patients who were randomized to receive a pexelizumab bolus, bolus plus infusion, or placebo around the time of CABG. Cognitive function was assessed preoperatively and on postoperative days 4 and 30.

The researchers’ findings are published in the October issue of Stroke.

As noted, pexelizumab therapy had no effect on overall cognitive function or on the primary endpoint, a composite of all-cause mortality, MI, left ventricular dysfunction, and new central neurologic deficit on postoperative day 4.

Pexelizumab did seem to protect against decline in the visuo-spatial cognitive domain, the researchers note. By the fourth postoperative day, 56% of control subjects had experienced a 10% or greater drop in this domain compared with 40% of patients treated with pexelizumab bolus and infusion (p = 0.003). At postoperative day 30, the corresponding rates were 21% and 12% (p = 0.016).

“Our detection of an improvement only in the visuo-spatial domain is a concern but is consistent with previous reports on pexelizumab and with potential mechanisms of injury during cardiac surgery,” the authors state. “A larger trial is necessary to further assess the significance of this improvement in only the visuo-spatial domain.”

Pexelizumab is manufactured by Alexion Pharmaceuticals, which sponsored the current study together with Proctor and Gamble Pharmaceuticals.