March 24, 2012 (Chicago, Illinois) — A small pilot study has shown that the addition of bindarit (Angelini Pharma, Rome, Italy), an anti-inflammatory compound, significantly improves six-month angiographic outcomes in stable coronary artery disease patients treated with a bare-metal stent. Investigators report that bindarit, an oral agent that selectively inhibits monocyte chemotactic proteins, reduced in-stent late loss compared with placebo in patients treated with bare-metal stents.
Presenting the results during a featured interventional session here at the American College of Cardiology 2012 Scientific Sessions, lead investigator Dr Antonio Columbo (Columbus Hospital, Milan, Italy) noted that in models of vascular injury, he and others previously showed that bindarit reduced neointimal formation by reducing smooth-muscle-cell proliferation and migration. In addition, bindarit reduced neointimal macrophage content, an effect related to monocyte chemotactic protein-1 (MCP-1) inhibition.
In this latest phase 2 pilot study, investigators hypothesized that treatment with bindarit for six months would reduce in-stent late loss in stable, symptomatic coronary artery disease patients undergoing elective PCI. Columbo noted that "it was not easy to enroll stable patients with bare-metal stents due to the current and sustained increase in usage of drug-eluting stents." In total, 48 patients were randomized to treatment with bindarit 300 mg twice daily, 49 patients were randomized to treatment with bindarit 600 mg twice daily, and 51 patients were randomized to placebo.
In terms of the primary end point, in-stent late loss was 0.74 mm in both bindarit treatment arms and 1.05 mm in the placebo arm, a statistically significant difference (p=0.02). There was no significant difference in rates of major adverse cardiovascular events, although the study was not powered for clinical outcomes. Adverse events were also similar between the high-dose bindarit arm, low-dose bindarit arm, and placebo.
Speaking during the interventional session, Columbo said the late loss observed was in the middle range of what is typically observed with drug-eluting stents, but pointed out that bindarit won't really become valuable until late-loss rates with the drug decline to 0.4 mm at six months.
Next steps for investigators include another pilot study, this time with just one dose, but using a loading dose given the day before the procedure. While Columbo noted that the field is very crowded with other interventional options for stable coronary artery disease patients and the cost of getting the new drug to market is expensive, Dr George Dangas (Mount Sinai Medical Center, New York) believes it might be an option worth pursuing, considering that there are many countries that still use bare-metal stents.
Dr Ted Feldman (NorthShore University HealthSystem, Evanston, IL) asked Columbo about testing the drug in patients at high risk for restenosis, such as those with longer lesions or smaller lesion diameters, but Columbo wasn't keen on the idea. "When you go to high risk, I always like to say it's like testing antibiotics in septic shock," said Columbo. "It would demand too much of an effect."
Heartwire from Medscape © 2012 Medscape, LLC
Cite this: Anti-Inflammatory Compound Reduces In-Stent Late Loss in PCI With Bare-Metal Stents - Medscape - Mar 24, 2012.