Drug eluting stent data evaluated

Last year, researchers from the University of Pennsylvania School of Medicine, in the US, studied Medicare data to identify 72,000 patients who received drug eluting stents during a nine-month period in 2003 – the first year the devices were approved for use in the US. Overall, the findings showed a clear survival benefit compared to a control group of patients who received bare metal stents – at 90 days, 1 year and 2 years, patients with drug-coated stents were less likely to die. More recently, data from the Cardiovascular Research Foundation has shown that drug eluting stents are more effective and are equally safe as baremetal stents. HORIZONS-AMI (Harmonising Outcomes with Revascularisation and Stents in Acute Myorcardial Infarction) study, showed that in heart attack patients undergoing angioplasty, the use of paclitaxel-eluting stents reduces rates of target lesion revascularisation and binary angiographic restenosis when compared to the use of bare metal stents after one year. The randomised trial, involving over 3,000 patients worldwide, evaluated the safety and efficacy of the TAXUS Express2 paclitaxel-eluting coronary stent system, from Boston Scientific, in comparison with bare metal stents. The drug eluting stents were not found to be inferior to bare metal varieties in terms of safety – including risk of death, stent thrombosis and stroke.1 However, paclitaxel-coated stents are also now being used in the treatment of blockages in arteries outside the heart for patients with peripheral arterial disease (PAD). This presents very different challenges to coronary applications – stents used in the leg are subjected to intense stresses through constant movement and impact to the area. “Between 10% and 12% of the population with a Western-diet suffer from peripheral arterial disease, but surgical approaches in the past have not always been optimum and there are a significant number of limb amputations each year,” commented Rob Lyles, global leader of the peripheral intervention business unit of Cook Medical. “With increased awareness of the issue, the medical community is currently focusing its efforts on the problem and looking for better options for patients. “Key challenges with the use of stents have included restenosis. In fact, statistics show that up to 40% of patients will suffer from a re-narrowing of arteries over time, making it necessary to repeat the procedure. The latest generation of drug eluting stents are designed to help prevent the re-narrowing the arteries, but those used in the leg continue to present significant challenges – as they need to be highly durable, withstand tough mechanical forces and last for a long time. Unfortunately, incidents of fractured stents occur all too frequently, leading to undesirable levels of revision surgery.” Cook Medical is achieving progress in tackling this issue, however. Preliminary data on trials on the drug eluting Zilver PTX peripheral stent, used to treat blockages in the critical thigh artery, show that 82% of patients were free from reintervention at two-year follow-up. The Zilver PTX Registry study, involved 792 patients from across the world. Data were compiled at 12 and 24 months for 593 patients and 177 patients respectively from the registry study, which enrolled a broad spectrum of patients, including those with complex lesions (e.g. long lesions, total occlusions, in-stent restenosis). The corresponding event-free survival (EFS) rates were 87% and 78%, and freedom from TLR (target lesion revascularisation) was 89% and 82%. Clinical measures that included anklebrachial index, Rutherford score, and walking distance and speed scores showed significant improvement at six and 12 months and were maintained through 24 months. Detailed evaluation of stent X-rays demonstrated excellent stent integrity through 12 months, confirming previously published results showing 99% completely intact stents with a mean follow up of 2.4 years in the challenging superior femoral artery and popliteal arteries, including behind the knee locations.2 “The results are extremely encouraging as it is the first time paclitaxel-coated stents have been used in the treatment of blockages in arteries outside the heart,” said Zilver PTX global principal investigator, Dr Michael Dake, professor in the department of cardiothoracic surgery at Stanford University Medical School and medical director of the cath/angio laboratories at Stanford University Medical Center. “Patients treated with the Zilver PTX had a very low complication rate and required fewer re-interventions.” “The advantage of using nitinol, which is a metal with ‘shape memory’, is that it will ‘bounce back’ to its intended shape despite the stresses encountered,” Rob Lyles explained. “Early stent designs often fractured under the movement of the leg. But this particular stent design has a fracture rate of less than 2%. To put this is into perspective, a number of other stents on the market currently have facture rates of between 30% and 50%. Fractures have sharp edges and can further irritate the vessel. Although it is not proven that fractures cause restenosis, there are strong indications that this is the case. “The design also eliminates the need for a polymer, which is typically used in conventional drug eluting, coated stents. This acts as the ‘glue’ that ensures the drug adheres to the stent, but in recent years there have been concerns over a possible link between polymers and thrombosis in cardiac patients. The vessel does not heal in the same way that it does with a bare stent. The ideal approach in our view, therefore, is to use a stent with a drug, but without a polymer.” Rob Lyles explained that the paclitaxel inhibits the smooth muscle cells of the artery, which contribute to part of the process of restenosis: “The drug works by limiting cell division. As the vessel is injured and it heals, we want to promote healing but do not want an overproduction of cells that could re-narrow the vessel with a scar. As it is a derivative of an antibreast cancer drug, it is also well proven,” he commented. “The superior femoral artery is a particularly challenging area for clinicians as, in the past, they have not had very satisfactory options or results,” Rob Lyles pointed out. “Angioplasty typically fails 70% of the time, but the data shows that this technology will dramatically reduce the rate of target lesion revascularisation – down to a little as 6%,” he added. “In many cases, clinicians are trying to reduce pain, but in extreme cases, blocked arteries may result in severe ulcers and gangrene. The quality of life for these patients is greatly diminished, while gangrene can prove fatal. If a clinician cannot open these vessels, the only option is to amputate. “Imaging may indicate that it is possible to restore blood flow, but in 70% of cases an angiographic study is not carried out before amputation is performed. This is of great concern as, statistically, once a patient has an amputation, their life expectancy after the procedure is typically just two years – the mortality is very high,” he continued. In addition to the human impact, Rob Lyles also highlighted financial benefits associated with the technology – by eliminating the cost of repeat operations, the savings could be significant for healthcare organisations.

Sirolimus-eluting stents

Six-month data from clinical trials of a sirolimus-eluting coronary stent (from Johnson & Johnson company, Cordis) has also now been released. The company reported superior results in reducing tissue growth within the stent, which can lead to repeat procedures compared to another leading drug eluting stent. In addition, no reports of stent thrombosis were reported in patients treated with the Nevo stent through six months. The results of the Nevo RES I study comparing the Cordis drug eluting stent with Boston Scientific’s Taxus Liberte stent were presented during “Late Breaking Clinical Trials” at EuroPCR, a conference aimed at physicians specialising in interventional cardiovascular medicine. Nevo uses RES Technology, which incorporates hundreds of small reservoirs, each acting as a depot into which drugpolymer compositions are loaded. The design allows drug delivery from a stent with a surface that is 75% bare metal on insertion and which becomes purely bare metal following drug delivery, with polymer bioresorption in approximately three months based on in vivo data. The Nevo sirolimus-eluting coronary stent had lower in-stent late lumen loss. Specifically, late lumen loss was reduced by 64% in the Nevo arm as compared to the Taxus Liberte arm (0.13 mm compared to 0.36 mm, p<0.001). In-stent late lumen loss, which is tissue growth within a stent, reduces the diameter of the lumen thus restricting blood flow through the stent and can potentially lead to major adverse coronary events, also known as MACE. Angiographic restenosis was reduced 86% (1.1% in the Nevo arm compared to 8.0% in the Taxus Liberte arm, p<0.002). Nevo also reduced the incidence of MACE (major adverse coronary events) by more than 40% (4.1% vs. 7.0% respectively; p=0.226). Patients treated with Nevo had numerically lower rates of events with respect to target lesion revascularisation (1.6% for NEVO vs. 3.2%; p=0.33) and the composite of death or heart attack (2.6% vs. 4.3%; p=0.26).