Future Research

This section discusses the future of drug-eluting stents, particularly on research that is being conducted to solve current problems.

Current Problems with Drug Eluting Stents

There are several current problems with drug-eluting stents that provide room for improvement. A few problems of these problems are listed below.

Some patients may show an allergic response to contrast agents or heparin used when visualizing coronary arteries to find evidence of coronary artery disease.
Immune response is a problem during stent placement, since the implanted stent is a foreign object to the body. The body's immune response may result in scar tissue to form around the stent, or it may cause clots to form on the arterial wall.
During advancement or removal of the catheter, the coronary artery may be perforated, although this is rare. Once the catheter is removed from the peripheral artery, the artery may fail to properly heal, causing hematoma.
There may be movement of the stent as it is sliding from the balloon into the vessel, known as embolization.
Excess bleeding may occur during the operation that would require a blood transfusion.
There may be infection and/or pain at the access site.
Restenosis or occlusion (which describes the re-clotting or re-narrowing of the coronary arteries after treatment) has been a problem ever since stents were first used.
Thrombosis (the formation of a clot inside the blood vessel) may occur during or after the procedure. The patient must continually take aspirin to prevent late stent thrombosis.
Tissue proliferation may also cause re-narrowing of the blood vessels.
After going through a stent procedure, the patient may have to remain on some medication. For example, an antiplatelet drug must be taken to prevent clot formation.
A big disadvantage with drug eluting stents is that there is not much long term data available due to its recent development.

The Future of Drug Eluting Stents

There are several areas of research underway that are aimed at improving the current methods of treating coronary artery disease. Research is being conducted to improve the three main components of a drug eluting stent: the scaffolding, the carrier, and the drug.

The Scaffold

Scaffolding alternatives, particularly biodegradable frameworks, to replace the use of metal stents are currently under investigation. One research study conducted by Heublein, et al. is developing stents consisting of magnesium alloys by testing the degradation kinetics of the material. The stent prototype consists of the magnesium based alloy AE21, which has an expected 50% loss of mass within six months. The study implanted stents in 11 pigs, and no thromboembolic events occurred with any of them. They concluded that implants that degrade by biocorrosion consisting of magnesium alloy is a realistic alternative for future coronary stents.

The Carrier

There is also much research in developing new methods for stents to locally administer the drug. One study by Tsuji, et al. is looking into a new drug-eluting polymer made with poly-L-lactic acid polymer mixed with tranilast. Transilast is an anti-allergic drug that inhibits the proliferation of vascular smooth muscle cells. The hypothesis in their research is that completely polymer stents is superior to polymer-coated metallic stents, since drug-mixed polymer stents can be loaded with a bigger dose of the drug. Studies that compare the drug delivery efficacy of pure polyer stents versus polymer-covered metallic stents are still underway. Another study by Vogt, et al. is looking into the use of another polymer made of a bioresorbable poly(D,L)-lactic acid (PDLLA) loaded with paclitaxel. Paclitaxel works similarly to transilast, in that it also inhibits vascular smooth muscle cell proliferation. The stents were tested in 36 porcine coronary arteries. They concluded that the novel polylactide stent showed sufficient stability, and may be another option in reducing restenosis rates in the future.

The Drug

Research for new anti-proliferative drugs that are delivered by drug eluting stents are also underway. Again, sirolimus and paclitaxel are the only two FDA approved drugs in eluting stents on the US market as of early 2007. However, a few other anti-proliferative drugs have reached human clinical trials and are currently being investigated. Zotarolimus is a new drug developed by Abbott designed for elution from phosphorycholine (PC) stents for the reduction of neointimal hyperplasia. Garcia, et al. developed a study examining the clinical application of coronary stents using zotarolimus by testing its ability to reduce neointimal hyperplasia in porcine coronary arteries. Zotarolimus binds to FKBP-12 to inhibit smooth muscle cell and endothelial cell proliferation. All arteries in the study showed near-complete healing and minimal toxicity. Another drug currently in clinical trials is everolimus. Everolimus is an anti-proliferative and immunosuppressative drug licensed by Guidant (which is now part of Abbott Labs). Everolimus works by absorbing to local tissue more rapidly than sirolimus, and possesses a longer cellular residence time. A study by Grube, et al. looked into the efficacy of everolimus on a bioabsorbable PLA-polymer-coated S-stent. They observed an acceptable safety profile without evidence of thrombosis or late stent malapposition, and concluded that everolimus might be a big contender in the future of drug eluting stents.

Next: References