Inside The Exam Room™ 01/08/2007
INTRAVASCULAR STENTS: Part 4
By Mark Ombrellaro, MD
Drug coated stents are used for the treatment of coronary (heart) artery disease and come in sizes that are 3.5mm diameter or less. These stent systems consist of a bare metal stent coated with a polymer adhesive that also has a drug bound to its surface. In the case of the Cypher stent, the drug is called Sirolimus (rapamycin) and for Taxus, the drug is Paclitaxel. The polymer binding agent is different for each type of stent and is used to provide time-release delivery of the drug molecule to the arterial wall. Most of the drug is released within the first 30 days following implantation. The mechanism of action of each of the specific drugs is beyond the scope of this article but the primary action of each medication is to reduce the inflammatory and scar formation process and reduce stent restenosis. For bare metal stents, failure due to restenosis can be as high as 30%. While with drug coated stents, restenosis rates are around 5%.
The recent news about drug coated stents are related to reports of an increased number of late deaths in patients who have been taken off Plavix after what was thought to be a complete course of antiplatelet therapy following stent implantation. For a moment, let’s consider the potential implications of these findings for patients who are being treated for coronary artery disease with drug coated stents. If the problem we are originally trying to solve is scar formation and restenosis, then delivering a medication to affect the healing process makes good sense. Using a stent as both a support matrix as well as a drug delivery platform is quite an elegant solution to such a problem. But what if the drug effects on wound healing and the scar formation process is too good and the stents heal very slowly or not at all? Have we actually been able to separate the beneficial aspects of wound healing from those which are detrimental as we originally hoped, or have we just delayed scar formation to a later time or prevented it all together? Completely Stopping wound healing means we now have both a foreign body (stent) and a raw surface area inside the arterial lumen on a continuous basis. Under these circumstances, stopping antiplatelet therapy would be expected to cause both clots and problems. Have we now traded a 30% chance of restenosis for 100% chance of prolonged antiplatelet use and increased the cost of coronary care? Obviously the problem is not to this extreme as most people who have stopped antiplatelet therapy do not experience any significant difficulties. There have been enough of these events, however, to get noticed.
In order to examine problem further, the FDA convened a special advisory panel on 12/7/06 to obtain further information about this subject. The outcome of the meeting was that there appeared to be more cases of late stent thrombosis (clotting) in drug eluting stents but the magnitude is uncertain. There does not appear to be an increase in the rate of death or heart attack when the devices are used in accordance with their labeling indications (“on label” indications). Using drug eluting stents in an “off label” fashion (i.e. not in strict accordance with their labeling guidelines) is associated with some increased risk, and the problem requires further investigation. The FDA concluded that the on-label use of drug coated stents is safe and effective. While some physicians are advocating treatment with Plavix and aspirin following drug coated stent placement indefinitely, the stent manufacturers continue to support current American Heart Association recommendations of use for 12 months. I think both the FDA and Industry did a commendable job of dealing with this issue. While several million drug eluting stents have been implanted over the last few years, the actual number of patients having late events when stopping antiplatelet therapy is very low at this point (numbering less than 0.01% of implants). Conducting ongoing monitoring and advocating on-label use of these devices are the appropriate response. As the recommended duration of antiplatelet use may be a moving target over the next several months, further information can be obtained from your physician, or the following resources: www.cordis.com, www.bostonscientific.com, or www.fda.gov .
Drug coated stents, used in accordance with their FDA approved labeling, are for use in the coronary circulation and remain safe and effective therapy. Stents used in all other non-coronary arteries (legs, renals, mesenteric, aorta, iliac, arms, and carotids) are bare metal and do not use drug eluting technology. Use of these types of stents in the rest of the circulation is not subject to the concerns of late mortality after ceasing antiplatelet therapy.