Drug Coated Stents

Sunday, September 24, 2006

Restenosis After Angioplasty and Stenting

Restenosis - the re-narrowing of a coronary artery - occurs within 3 – 6 months in 40 – 50% of patients who have angioplasty. This incidence was reduced to 20 – 30% with the use of traditional stents. Obviously restenosis remains a problem.
Angioplasty (and stent placement, since it is always accompanied by angioplasty) is a form of tissue trauma. A balloon is passed across an atherosclerotic plaque in a coronary artery and then it is inflated – thus compressing the plaque, and widening the opening of the artery. Compression (or "smashing," if you prefer) of the plaque is not a genteel process, and virtually always creates trauma to the blood vessel wall.
Restenosis is the formation of new blockages at the site of the angioplasty or stent placement. There are two major mechanisms for restenosis.
The first is by thrombosis, or blood clotting, at the site of treatment.
The risk of thrombosis is the greatest immediately after angioplasty, because the resultant tissue trauma tends to trigger blood clotting. This form of restenosis is greatly reduced by using anti-clotting drugs for a time during and after the procedure. (Click here for a quick review of why this clotting occurs within blood vessels.)
The second form of restenosis is tissue growth at the site of treatment. This form of restenosis – a proliferation of the “endothelial” cells that normally line blood vessels – tends to occur during the first 3 to 6 months after the procedure, and is not prevented by anti-clotting drugs. It can be thought of as resulting from “over exuberant” tissue healing and regeneration – more or less like scar formation – after the trauma of angioplasty.
Of course, recurrent atherosclerosis – the process that caused the coronary artery blockage in the first place – can also cause a recurrent blockage in a treated artery. But recurrent atherosclerosis accounts for very little restenosis during the first 6 months after angioplasty or stenting.
How can restenosis be prevented? As noted, the most immediate threat of restenosis – especially after stent placement – is thrombosis. For several years, clinical trials have been conducted to devise methods of reducing this form of restenosis. It has now been learned that administering special anti-platelet drugs called IIb/IIIa inhibitors (i.e., the drugs abciximab and eptifabatide) significantly diminish this problem.
Unfortunately (and does this seem to be a recurring trend?) it appears that fewer than 50% of patients who get stents are actually being treated with IIb/IIIa inhibitors, even though these drugs have been proven to significantly reduce restenosis. So: if you or a loved one are going to receive a stent, make absolutely sure that your doctor uses one of the IIb/IIIa inhibitors. Ask your doctor about this specifically, get a definitive answer, and hold him/her to it.
Now that doctors know how to prevent much of the immediate restenosis caused by thrombosis (and now that you know enough to make sure your doctor uses this knowledge), tissue growth (i.e., the scar-like) restenosis is the major remaining problem.
The most promising approach to this form of restenosis has been the drug coated stent. These stents are coated with drugs that inhibit the tissue growth that causes restenosis. Many drugs can inhibit the growth of cells. While many of them would be considered too risky to administer throughout the entire body, the idea of “delivering” a tiny amount of the drug directly to the tissue that needs to be inhibited is a very attractive one. Several companies are working on this process, and several drug-coated stents are undergoing clinical trials in Europe and the United States right now. The sirolimus-coated stent (the Cypher stent from J&J) was approved by the FDA in April, 2003, and has quickly become the most widely used stent. While all has not been wine and roses for this stent (read about
recent questions regarding the drug-coated stent here,) there is no question that the overall problem of tissue-growth restenosis has been greatly diminished with its use. It is expected that drug-coated stents currently under development will provide at least as much benefit as the Cypher.