October 24, 2012

MIAMI — A head-to-head comparison in a small study of a new biodegradable polymer-based sirolimus-eluting stent (SES), MiStent (Micell Technologies), showed the stent was superior to the zotarolimus-eluting stent (ZES) Endeavor (Medtronic) in terms of preventing late lumen loss. At nine months, quantitative angiographic data showed that the in-stent mean lumen diameter and in-stent diameter stenosis were also significantly better in patients treated with the novel SES.

The MiStent SES system contains a stent coating that includes sirolimus and the absorbable polymer. After the drug has been released, the polymer softens and is fully absorbed into the surrounding tissue in 90 days; what remains is the thin-strut cobalt-chromium coronary stent.

"The drug-eluting stent returns to the phenotype of a bare-metal stent, with all the benefit that these stents provide," lead investigator Dr David Kandzari (Piedmont Heart Institute, Atlanta, GA) told heartwire at TCT 2012. He added that these types of stents, with a biodegradeable polymer and reversion back to a bare-metal stent, represent the future workhorse stents in interventional cardiology.

Overcoming Shortcomings of Durable Polymers

The biodegradable polymer is designed to overcome the late failures of drug-eluting stents that have been attributed to their durable polymers. As has been reported previously, the durable polymer with drug-eluting stents has been blamed for everything from chronic inflammation and localized hypersensitivity reactions to positive remodeling and acquired incomplete stent apposition. Animal studies showed the MiStent significantly reduced inflammation and neointimal hyperplasia.

Today, Kandzari presented 18-month quantitative angiographic, intravascular ultrasound (IVUS), and optical coherence tomography (OCT) data from the DESSOLVE I first-in-human study of MiStent in 25 patients. Compared with eight-month data previously presented, long-term follow-up showed that late lumen loss and neointimal obstruction as measured by IVUS was unchanged, suggesting "stability in luminal dimensions." OCT data showed excellent stent coverage.

DESSOLVE II: Efficacy and Safety Outcomes

Outcome MiStent SES (n=103) Endeavor ZES (n=52) p
In-stent mean lumen diameter (mm) 2.58 2.28 0.001
In-stent diameter stenosis (%) 12.11 19.34 0.008
Late loss in lesion 0.19 0.34 0.029
Major adverse cardiac events 4.3 6.7 0.49

In DESSOLVE II, 181 patients with angina pectoris and documented ischemia were randomized 2:1 to the MiStent or Endeavor stent [1]. Kandzari told heartwire that the Endeavor stent was selected as the comparator because of its excellent safety profile and effective healing properties, although the stent is not well regarded for its ability to prevent late loss and restenosis (it has since been replaced by the Resolute stent, which has much better late-loss and in-stent-restenosis rates). In addition to superior angiographic outcomes with the MiStent at nine months, there was no difference in safety when compared with the Endeavor stent.

To support the case for biodegradable polymers, Kandzari pointed to the recently published COMFORTABLE-AMI study, a trial reported by heartwire . In that study, the use of a stent with a biodegradable polymer (BioMatrix, Biosensors Europe) in patients with ST-elevation MI (STEMI) resulted in an almost 50% lower rate of major adverse cardiovascular events (MACE) compared with use of a bare-metal stent. Boston Scientific is also in the biodegradeable polymer market with its Synergy stent. The platinum-chromium stent pairs a bioabsorbable PLGA polymer with an everolimus drug formulation.

Kandzari said there remains a great deal of excitement for stents that completely dissolve, not just the polymer, but there are some concerns about the integrity of the scaffold as well as other issues, namely the cost of these stents. Like others, he suspects the fully absorbable stents might be used only in a subset of the population, such as those without a lot of coronary calcification or easier-to-treat cases.