Reduced sirolimus systemic exposure and improved bioresorbable polymer properties: new allies for the treatment of patients with coronary artery disease

This prospective, first-in-man, open-label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug-eluting stent implantation (coated with sirolimus and bioabsorbable co-polymer) in patients with de novo coronary artery disease (the TCD-10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6-month angiographic and up to 12 months clinical follow-up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9-41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0-105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time-concentration curve, was 8.3 ng h/mL (range 6.47-28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity.