Drug-eluting stents (DES) are the standard percutaneous treatment strategy in patients with coronary artery disease (CAD). Their use has further reduced the incidence of restenosis and repeat revascularisation in single vessel de novo disease. These stents have bioactive coatings that, through a complex mechanism, allow the release of various anti-inflammatory and anti-proliferative drugs at high concentrations in the wall of the treated vessel without significant release into the bloodstream, to prevent restenosis of the vessel.
Sirolimus and paclitaxel have emerged as the two most effective drugs coating coronary stents. However, there have been questions raised as to whether there are any differences in the efficacy of these two drugs. Dr Adnan Kastrati, Professor of Cardiology at the German Heart Centre in the Technical University of Munich, recently conducted a meta-analysis of randomised trials comparing the sirolimus eluting stent (Cypher) with the paclitaxel-eluting stent (Taxus) to determine which drug is more effective in patients with CAD. Here, he talks to European Cardiovascular Disease 2006 about these findings and his views on DES.
Q: How do drug-eluting stents inhibit restenosis?
A: The predominant, almost exclusive, mechanism of lumen renarrowing after placement of coronary stents is neointimal formation due to smooth muscle cell proliferation. Putting drugs on stents (drug-eluting stents) that inhibit smooth muscle cell proliferation is shown to be effective for the prevention of restenosis.
Q: Which stents are better at decreasing restenosis?
A: Two drug-eluting stents (Cypher, a sirolimus-eluting stent, and Taxus, a paclitaxel-eluting stent) have been more thoroughly studied in various risk subsets of lesions and patients. Both have been associated with a remarkable reduction of restenosis risk compared with their bare-metal stent counterpart.
Meanwhile, there have been at least 10 randomised trials enrolling more than 5,000 patients that have compared Cypher stents directly with Taxus stents in different patient populations. In fact, the randomised clinical trial is the only acceptable tool of comparing different devices or drugs. These trials have clearly shown the superiority of Cypher over Taxus in terms of both angiographic and clinical restenosis. The benefit provided by Cypher is more pronounced among high-risk situations such as instent restenosis, diabetics, small coronary vessels.
Q: How have the results of the latest randomised trials affected the way interventionalists choose stents?
A: The results of the randomised trials with drug-eluting stents have led to the explosive diffusion of these devices for an increasing number of indications. It will not take a long time for drug-eluting stents to become the only stent in use in the catheterisation laboratories of Western countries. Interventional cardiologists are also becoming increasingly aware of the differences in performance between various drug-eluting stents and about the need to make the adequate selection especially in high-risk situations.
The meta-analysis of randomised trials compared the sirolimus-eluting stent with the paclitaxel eluting stent in patients with CAD, reporting target lesion revascularisation, angiographic restenosis, stent thrombosism myocardial infarction (MI), death and the composite of death or MI, during a follow up of at least six months.1 Eight trials (BAsel Stent Kosten Effektivit├ñts Trial (BASKET), CORPAL, Intracoronary Stenting or Angioplasty for Restenosis Reduction - Drug-Eluting Stents for In-Stent Restenosis (ISAR-DESIRE), ISAR-Diabetes, Intracoronary Drug-Eluting Stenting to Abrogate Restenosis in Small Arteries (ISAR-SMART 3), REALITY, SIRTAX and TAXi) involving 4,574 patients were included in the analysis.
Q: What are your thoughts on on-site stent coating?
A: On-site stent coating is a very interesting concept. It provides at least three advantages. First, it enables avoidance of the use of permanent polymers with all those concerns of long-term safety. Second, it provides a greater flexibility regarding selection of drugs and dosages that may prove to be safer and more effective; it assigns a more active role to the interventional cardiologist in the decision-making process. Third, it provides a more cost-effective approach in the time of increasing financial constraints. These are not simple theoretical considerations. A couple of recent studies have proven that the concept of on-site stent coating is feasible, safe and effective in an extent comparable to other approved drug-eluting stent platforms, with the potential of increasing advantages at long-term.
Q: What is the future of drug eluting stents?
A: It is not difficult to predict a bright future for drug-eluting stents. They are enabling interventional cardiologists to intervene in complex lesions and patients, including left main coronary artery, situations that have previously been an obvious indication for aorto-coronary bypass surgery.
They may enable us increasingly to treat vulnerable plaques, benefiting also from enhanced modern imaging capabilities.
New drugs and coating technologies are being investigated aiming at increasing the safety and efficacy of the drug-eluting stents, especially in high-risk patients. The fact that we stick to a prolonged dual antiplatelet therapy in patients who have received drug-eluting stents is a sign that further work is needed to eliminate the basis of our concerns. Ôûá