The CYPHER drug-coated stent (J&J), has made a huge impact in the treatment of coronary artery disease since it was first approved for marketing in April of this year. Over 50,000 of these stents have been used in patients during the first 3 months following its approval. The major advantage of the CYPHER stent is that it greatly reduces the incidence of restenosis (that is, of occlusion of the stent after it is placed.)
This month, however, J & J was compelled to send a "Dear Colleague" letter to doctors across the U.S. warning of a risk of clotting of the CYPHER stents within a few days of implantation. (The warning letter can be read on-line here.) Some patients have died as a result of this "subacute thrombosis," or SAT. The letter states that 47 incidences of SAT have been reported to the FDA so far with the CYPHER stent.
It is important to note that at least two types of restenosis is seen with stents. SAT is the first type - in these cases, either the procedure or the new stent itself activates platelets, causing the blood to clot within the stent, thus leading to occlusion of the coronary artery. If this clotting occurs, it almost always occurs within the first few days of the stent placement. This form of restenosis can be largely prevented by the aggressive use of antiplatelet drugs, usually for at least 3 months following stent implantation. The second - and more common - form of restenosis is caused by cell growth within the stent. This new cell growth occurs over a period of several weeks or months, and tends to be more gradual than SAT. Importantly, it is this second form of restenosis that drug-coated stents are designed to reduce. Drug-coated stents do nothing to reduce the incidence of SAT - only antiplatelet drugs can accomplish this.
It is unknown whether the incidence of SAT is increased with the CYPHER stent. The known incidence (approximately 1 out of 1000) seems similar to the incidence of SAT seen with other stents, but it is not clear that all episodes of SAT occurring with CYPHER have actually been reported. This month, J & J is instituting a formal registry that should answer this question.
What does seem clear, however, is that in their enthusiasm for the drug-coated stents, some doctors have used it inappropriately. Its inappropriate use may account for at least some episodes of SAT seen with CYPHER - at least, that's what J & J's "Dear Colleague" letter implies.
What are doctors doing wrong? At least two things, according to J & J. First, they are using sizes of the CYPHER stent that are inappropriate for the size of the artery being treated. (They are doing this because CYPHER is in short supply, and doctors are using whatever sizes are available to them.) Second, they are failing to use aggressive antiplatelet drug therapy. In addition, J & J reminds doctors not to use the CYPHER stent in situations where its safety and efficacy have not been proven. These situations include stenting during an acute myocardial infarction (heart attack), stenting vein grafts, and stenting complex blockages.
What's the bottom line?
As DrRich sees it, the subacute thrombosis described so far with the CYPHER stent does not yet reach alarming proportions. In fact, the described incidence is about what one would expect, though the true incidence won't be known for several will be better defined within a few months.In the meantime, it does seem likely that doctors are using this stent a bit too aggressively. If so, this "overuse" may be contributing to SAT. The enthusiasm for drug-coated stents is understandable, given the results of the clinical trials that led to FDA approval of this device. DrRich has even heard some cardiologists express the opinion that it would be unethical to use anything other than a drug-coated stent; and many patients been refusing to receive non-drug-coated stents. However, as the "Dear Colleague" letter points out, the CYPHER stent is not for everybody, and its misuse may lead to problems. Doctors should not use stents that are poorly matched for the size of the artery - drug-coated or not - and they should not use CYPHER stents in situations where its use has not been studied, and its safety and effectiveness have not been established. And patients (who are not entirely innocent bystanders in this case) should not demand that their doctors use drug-coated stents, and nothing else, no matter what. Such demands - with their implied threat to sue if a non-drug-coated stent is used and restenosis subsequently occurs - force doctors to behave in ways that may not be clinically optimal.
Whichever stents are used, doctors need to use aggressive antiplatelet therapy in order to minimize the risk of SAT; and patients receiving stents need to ask about antiplatelet therapy, and make sure their doctors are prescribing it.
