Inclacumab Shown to Reduce Heart Damage During Angioplasty

March 10, 2013—The American College of Cardiology (ACC) announced that findings from the SELECT-acute coronary syndrome phase II trial (SELECT-ACS) demonstrated that a single dose of an investigational anti-inflammatory drug, inclacumab, reduced damage to heart tissue during angioplasty. The study was presented at the ACC's 62nd annual scientific session in San Francisco, California.

According to the ACC press release, the SELECT-ACS trial investigators compared a single dose of inclacumab administered 1 hour before angioplasty with a placebo. Inclacumab is a human monoclonal antibody that blocks p-selectin. P-selectin, a molecule found in platelets and the cells that line blood vessels, is activated in response to inflammation, which can ultimately lead to tissue damage.

The study met its primary endpoint: decrease in levels of troponin I after angioplasty.

As summarized in the ACC announcement, the SELECT-ACS trial involved 530 patients with a median age of 61 years who were experiencing non-ST-elevation myocardial infarction. Patients were randomized to receive an infusion of inclacumab at 20 mg/kg, inclacumab at 5 mg/kg, or placebo 1 hour before angioplasty. The investigators measured heart damage using two standard molecular markers: troponin I and creatine kinase-MB (CK-MB). They were measured at baseline and at 8, 16, and 24 hours after PCI. The coprimary endpoints were the change in troponin I at 16 hours and 24 hours.

In patients receiving 20 mg/kg of inclacumab, troponin I levels decreased 22.4% more at 16 hours (P = .066) and 24.4% more at 24 hours (P = .05), compared with patients on placebo. CK-MB levels decreased 16.3% more at 16 hours (P = .088) and 17.4% more at 24 hours (P = .055), compared with patients on placebo.

Also, at 24 hours after angioplasty, 18.3% of patients on placebo had CK-MB increases of more than three times the upper limit of normal, a threshold that many clinical trials use to define a postangioplasty heart attack, compared with 8.9% of patients who received the higher dose of inclacumab (P = .051). The 5-mg/kg dose of inclacumab had no significant effects on the cardiac markers.

The investigators also measured p-selectin levels to see if they correlated with changes in CK-MB and troponin I. Levels did not drop significantly in the group that received 5 mg/kg inclacumab. However, levels dropped 19.2% with the 20-mg/kg inclacumab dose, compared with placebo (P = .0002).

The investigators analyzed a subgroup of patients who were not taking antiplatelet drugs called glycoprotein IIb/IIIa inhibitors. In patients not taking IIb/IIIa inhibitors, those who received the 20-mg/kg dose of inclacumab experienced a 36% decrease in troponin I at 24 hours (P = .008, compared with placebo).

Jean-Claude Tardif, MD, Director of the Research Centre at the Montreal Heart Institute and Professor of Medicine at the University of Montreal in Canada, is the study's lead investigator.

“Our hypothesis was that by using the p-selectin antagonist inclacumab, we'd be able to demonstrate vascular benefit,” commented Dr. Tardif in the ACC press release. “It was exciting to see that a single administration of inclacumab would yield clinical benefit.”

Dr. Tardif added, “If we're able to confirm these results in potential future studies, this drug could become part of the therapeutic armamentarium in modern cardiology. You could use this drug more widely, in all patients coming in with heart attacks, although that would require additional large studies.”