Polymer-free stent demonstrates noninferiority for in-stent late lumen loss

SAN FRANCISCO — A novel drug-coated stent that is both polymer- and carrier-free was noninferior vs. first-generation paclitaxel-eluting stents in terms of in-stent late lumen loss at a standard dose, but not at a low dose, with similar clinical event rates at 5 years, according to results presented at the TCT Scientific Symposium.

“The hypothesis is that this polymer-free drug release — this stent without a polymer — may reduce events caused by polymer stent coatings, especially late stent thrombosis, and eventually allow shorter need of dual antiplatelet therapy,” said Christian M. Spaulding, MD, PhD, professor at Paris Descartes University and interventional cardiologist at Georges Pompidou European Hospital, Paris. Spaulding presented the study results for Ricardo A. Costa, MD, PhD, of the Instituto Dante Pazzanese de Cardiology and the Cardiovascular Research Center, both in São Paulo.

Study design

Costa and colleagues enrolled patients with de novo coronary lesions aged at least 18 years in the first-in-human investigation of the BioFreedom biolimus-coated stent (Biosensors International). Inclusion criteria included symptoms of stable or unstable angina or the existence of a positive functional test for ischemia; a single de novo target lesion up to 14 mm in length, with stenosis 50% to 99% in the native coronary vessel (2.5-3 mm in diameter); acceptable candidate for CABG; and agreement to participate in all follow-up, including one angiographic re-evaluation.

Key exclusion criteria included the occurrence of MI within 72 hours of enrollment; left main ostial location; moderate or severe calcification noted on fluoroscopy; a target lesion involving a side branch larger than 2 mm in diameter; thrombus; documented left ventricular ejection fraction of less than 30% evaluated within 6 months of the procedure via echocardiography, during previous angiography or as measured during pre-procedure angiography; known hypersensitivity or contraindication to antithrombotic therapy; and the existence of a concurrent medical condition with a life expectancy of less than 18 months.

Altogether, 182 patients with 183 de novo coronary lesions were enrolled. Patients were randomly assigned, in a 1:1:1 ratio, to treatment with BioFreedom stents in a standard dose or a low dose vs. first-generation paclitaxel-eluting stents at four sites in Germany. BioFreedom stents were treated with biolimus A9 (BA9), a 31-membered triene macrolide lactone derivative of sirolimus that is a strong antiproliferative agent created for vascular applications, specifically drug-eluting stents. The primary endpoint was in-stent late lumen loss. Baseline and procedural characteristics were well matched among participants, according to the study results.

Results and implications

In cohort 1 (n = 75), in-stent late lumen loss was lower in the BioFreedom standard and low-dose groups vs. the paclitaxel-eluting stents group at 4-month angiographic follow-up (0.08 mm and 0.12 mm vs. 0.37 mm, respectively; P < .0001 for standard dose vs. paclitaxel and P = .002 for low dose vs. paclitaxel). At 12 months (cohort 2; n = 107), in-stent late lumen loss was 0.17 mm in the standard-dose group vs. 0.35 mm in the paclitaxel group (P = .001 for noninferiority; P = .11 for superiority). In-stent late lumen loss in the low-dose group (0.22 mm) did not reach noninferiority (P = .21).

Spaulding noted the “significant reduction of in-stent late lumen loss at 4 months between both groups” in his presentation.

At the 5-year point, among 175 of the original 182 participants, no significant differences were noted in regard to MACE (23.8% for the standard-dose group, 26.4% for the low-dose group and 20.3% for the paclitaxel group) and clinically indicated target lesion revascularization (10.8% for the standard-dose group, 13.4% for the low-dose group and 10.2% for the paclitaxel group). No definite/probable stent thrombosis were reported.

“This first-in-man study demonstrated the efficacy of a polymer, carrier-free BioFreedom coated stent with the standard dose of biolimus,” Spaulding said. “There was no significant difference in clinical outcomes up to 5 years. There was no safety concern in this first-in-man feasibility study, with absence of death and probable stent thrombosis in all groups.” – by Julia Ernst, MS

References:

Costa RA, et al. Polymer-free drug-coated stents. Presented at: TCT Scientific Symposium; Oct. 11-15, 2015; San Francisco.

Costa RA, et al. JACC: Cardiovasc Interv. 2015;doi:10.1016/j.jcin.2015.09.008.

Disclosures: Costa reports receiving speakers’ fees from Biosensors Europe SA, Daiichi-Sankyo and Medtronic. Spaulding or his spouse/partner reports receiving consultant and speakers’ bureau fees and honoraria from AstraZeneca and Medtronic and off-label products in cardiogenic shock and cardiac arrest from Impella and ECLS. Please see the full study for a list of all other authors’ relevant financial disclosures.