Positive Long-Term Results from LEADERS, BioFreedom FIM, ISAR-TEST 5

MIAMI BEACH, FLA.—Several studies involving polymer-free stents as well as a biodegradable-polymer biolimus-A9-eluting stent yielded good long-term results, according to several presentations at TCT 2012.

Patrick W. Serruys, MD, PhD, of Erasmus University, Rotterdam, the Netherlands, presented 5-year results from the LEADERS trial, a non-inferiority study comparing a biolimus A9-eluting stent (BES) with a biodegradable polymer and abluminal coating (BioMatrix Flex, Biosensors) with a sirolimus-eluting stent (SES, Cypher Select, Cordis). Biolimus A9, a sirolimus analog, is 10 times as lipophilic as the other limus agents, allowing it to be rapidly absorbed by local tissue.

LEADERS was an all-comers trial, with 1,707 patients randomized to either

BES or SES. After 5-year follow-up, 1,647 patients were available for analysis (96.5%).

The primary outcome of MACE (cardiac death, MI, and clinically indicated TVR) was 22.3% for BES patients and 26.1% for the SES patients; the difference was not significant for superiority (P=.071) but was significant for non-inferiority (P<.0001). A patient-oriented composite endpoint including all-cause death, any MI, and all revascularization was lower in the BES group at 5 years (see Figure). Definite stent thrombosis rates at 5 years were 2.6% in the BES patients and 4.5% in the SES group (P=.060). Serruys concluded that “abluminal coating… has a future in our treatments.”

BioFreedom FIM and polymer-free DES

The BioFreedom FIM trial also tested a biolimus- A9-eluting stent, though on a platform that does not use a polymer coating. The BioFreedom stent (Biosensors) has a micro-structured surface that holds the drug. Eberhard Grube, MD, PhD, of University Hospital Bonn, in Bonn,Germany, who presented results from the BioFreedom FIM trial, said this platform could reduce late events caused by polymer stent coatings.

The trial included 182 patients randomized to one of three groups: a BioFreedom standard dose group (15.6 mcg/mm; 60 patients); a BioFreedom low dose group (7.8 mcg/mm; 62 patients); and a group who received a paclitaxel-eluting stent (PES, Taxus Liberté, Boston Scientific; 60 patients). Baseline and procedural characteristics were similar across the groups. Previously presented at TCT 2010, the primary outcome of late lumen loss at 12 months showed the standard dose BioFreedom stent was noninferior to PES.

Grube presented the 36-month results at TCT 2012, which showed no significant differences across the groups with regard to a number of outcome measures. MACE (all death, MI, emergent bypass, or TLR) rates were 11.9% in the standard dose group, 18.1% in the low-dose group, and 10% in the PES group. There were no definite stent thromboses in any group in the trial.

“The next step would be larger trials powered for clinical outcomes to confirm these primary encouraging results,” Grube said. “The ability of this technology to reduce DAPT is conceptually attractive and should also be investigated.”

ISAT-TEST 5 Trial and dual DES

Lamin King, MBBS, of the Deutsches Herzzentrum in Munich, Germany, presented results of the ISAR-TEST 5 trial. The study compared the ISAR stent, a polymer-free device that releases sirolimus plus probucol (dual DES; 2002 patients), with the zotarolimus-eluting Resolute stent (ZES, 1,000 patients). Primary composite outcomes (cardiac death, target vessel-related MI, or TLR) at 12 months, published previously, showed noninferiority of the dual DES compared with ZES. The new results at 24 months showed a continuation of this trend, with a composite endpoint rate of 15.8% for the dual DES group and 15.9% for the ZES group (HR 0.98; 95% CI 0.81-1.19), indicating noninferiority. Definite stent thrombosis at 24 months was also similar between the two groups, and subgroup analyses showed no differences with regard to age, gender, or other variables.