SNOWMASS, COLO. — Some of the most exciting of the drug-eluting stent platforms working through the developmental pipeline have the potential to curb the vexing problem of late stent thrombosis, Dr. Robert M. Bersin said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.
Furthest along of these is the BioMatrix stent system being developed by Biosensors International. It consists of a stainless-steel stent, a poly-L-lactide polymer as the drug-delivery vehicle, and the drug itself, a sirolimus analogue called Biolimus A9.
The technologic advantage of BioMatrix is that its drug-delivery polymer is the first to be fully bioabsorbable. That means there will be no residual polymer to flake off or promote inflammation.
“This polymer will disappear over time with no coating left behind, which is one of the issues we are currently evaluating as a potential factor in late stent thrombosis,” explained Dr. Bersin, director of clinical research at the Washington Cardiovascular Research and Education Foundation, Seattle.
The sirolimus analogue is more lipophilic and elutes faster than the parent drug. It seems to be performing well, with an average in-stent late lumen loss at 6 months of only 0.26 mm, compared with 0.74 mm with a bare-metal stent (BMS). A trial to be reported later this year will give a good idea of how BioMatrix performs relative to drug-eluting stents (DESs) now on the market, he added.
A recent metaanalysis of all eight randomized prospective trials of the sirolimus-eluting Cypher stent and the paclitaxel-eluting Taxus paclitaxel stent clearly shows late stent thrombosis is a problem with both devices.
Thrombosis rates with the two were superimposable upon those of BMSs out to about 18 months. Then the curves diverged. At 3 years, the stent thrombosis rate was 1.1% with Cypher and 1.3% with Taxus. Each rate was an absolute 0.5% more than with BMS comparators.
“Late stent thrombosis is a big issue today with drug elution,” Dr. Bersin stressed. “This is a consistent issue with drug-eluting stents, regardless of brand.”
A recent analysis showed that prior brachytherapy was the strongest predictor of stent thrombosis in patients with a DES. Renal failure was second, followed by anatomically difficult features, such as bifurcation lesions, and diabetes.
Numerous manufacturers are developing fully biodegradable DESs constructed of poly-L-lactide or other polymers. Because the materials lack the mechanical strength of traditional stainless steel or cobalt-chromium, sophisticated designs have been used to increase radial strength. These stents will not only eliminate the obstacles to repeat revascularization posed by permanent metal stents, but they could also solve the late thrombosis problem.
Berlin-based Biotronik AG is conducting clinical trials of a magnesium alloy-based DES that biodegrades through controlled corrosion. The appeal is that it may provide a temporary metal scaffolding with the same strength and performance characteristics as a permanent BMS, Dr. Bersin said.
A new paradigm for restenosis prevention is being developed by OrbusNeich. Its Genous stent, rather than locally delivering cytotoxic drugs to curb an overzealous vascular intimal healing response, is designed to enhance function of endogenous modulators to promote more efficient healing.
The Genous metallic stent is coated with a fragment of antibody to CD34 in order to capture circulating endothelial progenitor cells to accelerate endothelialization. In animal studies, the BMS still had bare struts 48 hours after implantation, while the Genous stent was completely coated with a monolayer of endothelial cells. Clinical trials are ongoing in Europe.
“This could offer a clear advantage in terms of stent thrombosis risk, especially in patients unable to take high-level antithrombotic agents for various reasons,” the cardiologist said.
Another highly original stent platform design is a Conor DES containing nearly 600 laser-cut wells in the struts. These wells can be filled with two different drugs with a barrier layer in between—for example, an antiproliferative agent on the stent's intimal side and an antithrombotic drug on the luminal side. At least that's the plan; so far the wells have held only a single cytotoxic drug in trials.