Delegates at the CX Symposium on Saturday 4 April 2009 sided with Marc Bosiers, AZ St Blasius, Dendermonde, Belgium, in saying that – at least in the current economic climate – drug-eluting stents “are dead in the water”.
Bosiers was debating Lindsay Machan, Associate Professor, Faculty of Medicine, University of British Columbia, on the issue of drug-eluting stent use in the superficial femoral artery.
The debate followed the presentation of data from two significant trials of drug-eluting stents: STRIDES and ZILVER PTX.
Bosiers estimated costs, using an average of 1.5 stents per procedure, of €3,000 for treatment with a drug-eluting stent, compared to just €1,500 for a bare-metal stent.
Bosiers pointed to the SIROCCO (Sirolimus coated cordis self-expandable stent) trial that provided the first published outcomes following the use of drug-eluting stents in the infrainguinal vasculature. The authors of this study concluded that that no significant difference could be found between the bare metal and the sirolimus-eluting SMART stents.
“Basically, the only thing that drug-eluting stents have proven until now, is that they give a guaranteed doubling in costs to have the same number of patients with a patent vessel after one year.”
Machan, opposing Bosiers’ position, argued that SIROCCO used early-generation technology, designed originally for the coronary artery, and that the “superb results” with drug-eluting stent in the coronary circulation are unlikely to be repeated in the femoropopliteal segment by employing the same dose and delivery methods.
“Of course we don’t yet have level one evidence that drug-eluting stents offer a benefit over bare-metal stents, or that they’re cost effective.” said Machan.
“What we do have is very interesting and compelling early data, and we have the results of two prospective, randomised trials to come. I’d ask you to think of the first commercially-available stent graft, and how often we saw proximal row separation. But if we’d have thrown it out then, think of where we’d be now with endovascular aneurysm repair.”
CX delegates, however, voted narrowly for the motion that “Drug-eluting superficial femoral artery stents are dead in the water”.
STRIDES is a single-arm trial of the Dynalink-E Absolute everolimus-eluting peripheral stent system [Abbott] in patients with peripheral vascular disease.
The primary endpoint was initially six-month restensosis rates. “Because the 12 month angiography is important, it can measure late lumen loss in addition to restenosis rate, so we have decided to wait for the 12-month follow-up before we summarise with the restenosis rates,” explained Johannes Lammer, Medical University of Vienna, Austria.
“We know that there has been one randomised trial comparing bare metal stent with drug-eluting stents, and that was SIROCCO. And at two years, there was no difference between the two treatments.
“So what was the problem with the SIROCCO trial?” he asked. “In SIROCCO, the sirolimus was eluted very rapidly, within a very short period of time. “Therefore, in order to challenge the disadvantages of the SIROCCO stent, the everolimus-eluting stent delivers a higher dose, and releases the drug slowly.”
Instead of data regarding the restenosis rates, Lammer presented a pharmacokinetic substudy, which mapped this drug delivery.
Plasma concentrations of everolimus were measured at one, four, and eight hours, at discharge, and at one-month follow-up in 26 patients.
“The stents, whether they were short or long, had the same concentration of everolimus per centimeter squared, but, of course, a longer stent had a higher total systemic drug concentration, going up to 3,777μg.”
“It was also interesting that systemic drug concentration was measurable up till 30 days due to the prolonged drug release.”
Lammer concluded that Dynalink-E releases everolimus slowly over several months, with a maximum systemic concentration (Cmax) of everolimus after implantation of 80-200 mm stent length was 3.2±1.5ng/ml, well below concentrations observed after oral everolimus dosing and below sirolimus concentration after SIROCCO stent implantation.