Serp-1 Anti-Inflammatory Properties Show Promise in ACS Patients Undergoing PCI

November 29, 2010—Jean-Claude Tardif, MD, et al conducted a study to evaluate the safety and efficacy of Serp-1, a myxoma virus-derived serpin, in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention. The background of the study is that Serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. Vascular inflammation can lead to plaque instability and ACS, and viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. The investigators published the findings online ahead of print in Circulation: Cardiovascular Interventions.

As detailed by the investigators, this double-blind pilot trial included 48 ACS patients undergoing percutaneous coronary intervention who were randomly assigned to Serp-1 at doses of 5 µg/kg (n = 19) or 15 µg/kg (n = 17) or to placebo (n = 12). Serp-1 was given by intravenous bolus immediately before intervention and 24 and 48 hours after the procedure. Patients were assessed for safety (primary objective) and efficacy outcomes including biomarker analysis. In-stent neointimal hyperplasia was evaluated by intravascular ultrasound at 6 months.

Key safety outcomes including coagulation parameters and adverse events did not differ between Serp-1 and placebo groups. A dose-dependent reduction in troponin I levels was observed with Serp-1 at 8, 16, 24, and 54 hours (P < .05) and in creatine kinase-MB levels at 8, 16, and 24 hours after dose (P < .05). The composite of death, myocardial infarction, or coronary revascularization occurred in 2 of 12 patients with placebo, in 5 of 19 in the low-dose group, and in none of 17 patients with the high dose (P = .058). Intravascular ultrasound did not detect changes in neointimal hyperplasia among groups.

According to the investigators, this is the first study of a viral serpin showing safe use in ACS patients. They concluded that the significant reduction in myocardial damage biomarkers supports further assessment of Serp-1 in ACS patients undergoing stent deployment.