Everolimus for stent-based intracoronary applications

Everolimus, a novel proliferation signal inhibitor initially developed for the prevention of allograft rejection after organ transplantation, is a potent anti-proliferative and immunosuppressive agent. Compared to sirolimus, everolimus absorbs to local tissue more rapidly and possesses longer cellular residence time and activity. The stent-based intracoronary elution of everolimus was first investigated by BioSensors International using a bioabsorbable-PLA-polymer-coated S-Stent for drug delivery. Following preclinical animal studies that demonstrated excellent safety and efficacy of this device, the clinical FUTURE trial program was initiated. FUTURE I and II were designed to demonstrate safety and feasibility of the everolimus-eluting stent in a small patient population with focal de novo coronary lesions. At follow-up, an acceptable safety profile without evidence of stent thrombosis or late stent malapposition was observed. Moreover, these studies revealed a remarkable reduction of neointimal proliferation with everolimus-eluting stent implantation versus procedures utilizing bare-metal stents. Guidant Corporation licensed the exclusive rights to both the S-Stent and the bioabsorbable drug delivery platform. Guidant will conduct two pivotal trials (FUTURE III and IV) in order to demonstrate the efficacy of this stent design. FUTURE IV will make a non-inferiority comparison between everolimus and the already-approved drug eluting stent systems. Given the pooled results of FUTURE I and II, there is already some evidence suggesting that the everolimus-eluting stent is as potent a suppressor of reactive neointimal ingrowth as the sirolimus-eluting CYPHERTM stent. The everolimus-eluting coronary stent might shortly be established as a new and promising contender in the field of drug eluting stents for treatment of coronary heart disease.