New Trends in Cardiology Devices - What is the Future of Stents?

Coronary stents have become the most exciting story in interventional cardiology. These devices have offered an increasingly effective solution to the problem of coronary vessel restenosis. Following balloon angioplasty procedures, approximately 30% of coronary arteries are affected by this complication. The launch of bare metal coronary stents in the 1990s went some way towards alleviating this problem but the bare metal stents continue to be associated with a restenosis rate of around 25% of patients being affected 6 months after stent insertion. Drug eluting stents attracted increasing attention during the 1990s as potentially offering a more effective way to lower the rate of restenosis to single figures.

Drug Eluting Stents

At the 2004 Medical Innovation Summit at the Cleveland Clinic Foundation, Guy Lebeau, Company Group Chairman for Cordis, outlined what the future may hold for cardiology technology. He described how drug/device based solutions were expected to be used in up to 20% of cardiology procedures by 2010.

Drug eluting stents are certainly helping to realise this forecast. The 2005 global market for drug eluting coronary stents is predicted to reach $5 billion. Cordis’ Cypher stent was released in the European and US markets in 2003 and, at that time, a revolution was predicted in the manner in which interventional cardiology procedures were to be carried out. However, since Boston Scientific entered the European market in 2003 and the US market in March 2004 with the Taxus stent this product has allowed Boston Scientifc to successfully challenge Cordis, gaining market share overall and winning approximately two thirds of the US market in its first year of launch.

These two companies, Cordis and Boston Scientific remain locked in a battle for dominance of the drug eluting stent market. Altering physician perception and practice is a key marketing effort, underpinned by the continued publication of clinical trial results.

Results from the Cordis sponsored REALITY trial were recently published. This trial compared TAXUS and Cypher in 1386 patients. This trial did not demonstrate a significant difference in restenosis rates between the two stents, making other differences, such as ease of insertion and contribution of stent linked blood clots (a rare complication associated with drug eluting stents), a more significant issue. Boston Scientific have countered problems associated with the original TAXUS stent through the launch of the TAXUS Liberte stent in January, 2005. This product offers a refinement on the original Taxus stent that improved the conformability of coronary stents, making it possible to insert drug eluting stents in more difficult to reach coronary vessels.

This development reflects clinical interest in the need to be able to access small calibre coronary vessels with drug eluting stents. Successful drug eluting stents of the future will be those that are able to access challenging anatomies whilst at the same time minimising endoluminal injury. These demands may require features such as limited balloon extension or self expanding stents which are able to deploy at lower pressures. Stent design will also require a balance between low profile, flexibility and ease of deployment and the requirement for sufficient endoluminal surface coverage. Newer alloys such as cobalt chromium may make this more possible in the future. Both Medtronic and Guidant are working on cobalt chromium drug eluting stents.

Other companies are working hard to enter the drug eluting coronary stent market. In particular, as illustrated by the table below, Guidant has been active in this area and has announced the planned release of their Champion drug eluting stent system in 2005, following the successful completion of FUTURE IV, a 975 patient strong clinical trial. Guidant has also announced that in 2006 they plan to use their everolimus drug eluting system on a novel cobalt-chromium based scaffold (MULTI-LINK VISION TM).

A further development that has attracted interest is a stent coated with a drug that stimulates the endothelium to grow around the stent, reducing the risk of stent-related blood clots developing, by a small company called Orbus. The Genous Bio-engineered Surface, uses antibodies to capture the patient's endogenous Endothelial Progenitor Cells (EPCs). EPCs form an endothelial layer over the stent which should inhibit restenosis whilst also preventing the formation of blood clots.

Medtronic’s ENDEAVOUR trial has thus far demonstrated a benefit over comparable bare metal stents, although additional trials are ongoing prior to FDA approval. In Europe, Medtronic is aiming to launch its drug eluting stent by the summer of 2005. The introduction of this new stent to the European market may be patchy, since Medtronic has so far been unable to secure reimbursement in France and Belgium, although the company hopes that this will be rectified by the end of 2005. A US launch is not planned until 2007.

Abbott Laboratories is developing the TriMax stent, composed of a stainless steel tantalum composite. This stent elutes ABT-578 over a 30 day period and is expected to enter a 100 patient clinical trial in Europe in late 2005.

Other aspects of stent technology are also in various stages of development. For example companies are looking at changes in the materials used in stents with a view to allowing movement from the conventional metal-based stent framework towards polymer-based stents. The US Patent and Trademark Office has recently approved a patent for the new use of hydrogel as a hydrophobic macromer that can trap the agent utilised by a drug eluting stent. Other patents include biodegradable polymer designs that act as a matrix for pharmaceutical agents in drug eluting stents and a hydrophobic polymer covered with linked heparin as the outer layer of the structure aimed at the prevention of thrombosis in addition to the prevention of restenosis. It is possible that a heparinised coating on a stent may contribute to the prevention of some of the early clotting problems that have occurred with drug eluting products.

Further developments may include biodegradable drug eluting stents which allow a patient to have subsequent cardiology procedures, such as CABG and post-stent placement.

Will there be a role for stents in the future?

It is possible that the long term future of cardiology may be one in which stents do not feature, or as is more likely have a much reduced role. A number of new technologies that could replace stents in the future have been described by key opinion leaders in the area.

Some of these newer technologies include injection catheters, local catheter diffusion, locally activated cardiology drugs, innovations in polymer technology and cryotherapy. With regard to injection catheters, Cordis is collaborating with GenVec, a biopharmaceutical company focussing on cancer, cardiology, ophthalmic and infectious diseases, on the NOVA (NOGA Delivery for Angina) trial. This trial is studying the clinical benefits of BIOBYPASS angiogen-guided delivery direct to targeted regions of the heart using Cordis’ Nogastar mapping Catheter system and Myostar injection catheter. In March 2005 GenVec announced the start of Phase IIB of the NOGA trial, which will consist of a randomised, placebo controlled trial of BIOBYPASS for the treatment of severe coronary artery disease.

In other developments, Cryocath, a medical technology company specialising in catheter and probe-based cryotherapy products, is currently carrying out pre-clinical work evaluating the efficacy of cryotherapy in coronary restenosis and also in peripheral restenosis, and reports that initial results are encouraging.

In the near future it is unlikely that the dominance of the coronary stent will be significantly challenged but the potential for new, less invasive technologies that are easier to insert or implant cannot be ignored. It has been reported that whilst interventional cardiology procedures are expected to increase threefold by 2010, the availability of interventional cardiologists is not expected to keep pace. Demand for interventional coronary procedures is currently outstripping the number f interventional cardiologists available to carry out the procedures. It will become more necessary clinically to explore alternative options that are less demanding in terms of time and cost. These options may focus on targeted drug delivery and on alternative technologies which benefit patients in terms of ease of procedure and subsequent quality of life, while also allowing cardiology professionals to better manage workflow.

Author: Rachel Lewington, Consultant