Coating stents to prevent in-stent restenosis or reduce it is not a new idea, but it has taken years to be developed into a marketable stent product. Initial trial results have suggested that drug-eluting stents hold the key to ‘zero restenosis’in coronary arteries. The clinical and financial implication of this are enormous, with the coronary stent market alone is set to triple over the next three years.
Coronary stent status
Cordis’CYPHER sirolimus-eluting has received CE Mark approval. Cordis presented, for CE Mark approval, one-year follow-up data, which showed a significantly lower major adverse cardiac events rate compared with that of
the control, a subacute thrombosis rate comparable to that of the control, and a target
lesion revascularisation (TLR) rate significantly lower than that of control. Cordis’RAVEL (Randomised Study with the Sirolimus-eluting VELocity Balloon Expandable Stent) trial was the first large-scale stent study to document sustained zero restenosis at six months post treatment.
In the US, the CYPHER stent is in a pivotal large scale FDA trial (SIRIUS). Nine-month results from the first 400 patients enrolled in the SIRIUS 1,100-patient study were presented at EuroPCR 2002. The SIRIUS trial is the most recent in a series of studies evaluating the safety and efficacy of the CYPHER stent in reducing reblockage of de novo coronary artery lesions. The 400-strong patient subset at eight months showed 2.0% binary in-stent restenosis with sirolimus, compared to 31.1% in the control group (a 94% reduction). In lesion restenosis rates were 9.2% in the sirolimus arm, compared with 32.2% in the control group.
Meanwhile in June 2002, Boston Scientific submitted an application for a CE Mark for its TAXUS paclitaxel-eluting stent system. In the US, this system is currently undergoing a clinical trial (TAXUS IV), having enrolled 1,172 patients at 80 sites, to collect data for US product commercialisation.
Guidant has now started, on behalf of Cook, enrolment of patients for its DELIVER II trial designed to evaluate the benefit of the paclitaxel-coated ACHIEVE drug-eluting coronary stent system. The ACHIEVE stent system is manufactured by Cook, containing some components supplied by Guidant, and has been filed for CE approval. DELIVER II will be the largest drug-eluting stent trial to date, with a target enrolment of 1,500 patients in 100 centres. The study will follow patients implanted with the ACHIEVE stent system for a period of three years. The primary endpoint of the study is the target lesion revascularisation rate, a measure of long-term success. Good results with Cook’s paclitaxel-eluting V-Flex Plus PTX have been already been shown in the ASPECT and ELUTES trial protocols and approval in Europe is expected soon.
Angiotech Pharmaceuticals licensed to Cook co-exclusive rights to coat its devices with paclitaxel. However, this agreement has been found by the United States District Court for the Northern District of Illinois to disallow the agreement between Cook and Guidant relating to the development and distribution of paclitaxel-eluting stents. Ronald Dollens, president and CEO of Guidant, emphasised that despite this his company will continue to pursue regulatory approvals and commercialisation of the ACHIEVE stent system.
Medtronic is also in the drug-eluting stent game, and importantly has recently signed a deal with Abbott that will bring Medtronic the drug and polymer coating it was missing.
Making a mark
In the beginning, many interventional cardiologists were sceptical of drug-eluting stents. It was not known how localised the drugs effect might be and it was thought that some cell growth might occur between the drug-eluting stents’struts. The initial findings of ‘zero restenosis’in drug-eluting stent trials were received as a major breakthrough by the community of interventional cardiologists. These findings were almost too good to be true and some people are waiting to see if the disease condition returns a few years after the implantation. However, the ‘free of restensosis’period has been proved long enough for the industry to get very excited.
The growth of drug-eluting stent usage would be at the detriment of non drug-eluting stent sales. Therefore many of the companies in the stent supply industry are making investments in the development of drug-eluting stents, so as to not miss out on a fast growing business that will take sales away from their current non-coated stent products. These same companies have peripheral vascular stents and therefore changes to the product lines for peripheral applications are likely. Whether drug-eluting stents will be as successful for treating peripheral vascular disease remains an important question. Results from the SIROCCO trial, presented at ISET in January (Vascular News 13, page 18), have certainly caught the attention of interventional radiologists.
Drug-eluting stents are not ideal for all stenotic lesions. Even in coronary cases some patients are excluded from treatment with drug-eluting stents if the lesion is heavily calcified or the artery is thrombosed. Many peripheral vascular conditions may also require another form of treatment, and it remains to be proved that drug-eluting stents can be used as successfully in peripheral cases as they appear to be in coronary cases. However, if as suggested by the SIROCCO trial, drug-eluting stents perform well in the superficial femoral arteries, a region renowned for in-stent restenosis, they will probably perform well elsewhere. It may mean more stents are used in treating the lower limb occlusions, although some lesions might be considered unsuitable following the initial experiences of trials in peripheral applications.
Companies and endovascular specialists will need to redo the trial work for peripheral procedures to prove the efficacy of this method of treatment. Surgeons and radiologists will have to move quickly to ensure that the work does not go to interventional cardiologists, many of who are eager to stent peripheral lesions with drug-eluting stents.