At PCR, Drug-Eluting Stents Dominate the Discussion

At this year's Paris Course on Revascularization, drug-eluting stents, not surprisingly, dominated the discussions. Clinical concerns about the new therapy have now given way to practical, economic concerns.

This year's Paris Course on Revascularization (PCR) had many sessions focusing on future therapies and technologies based on vulnerable plaque and angiogenesis. But, not surprisingly, with European commercialization a year old and US marketing just beginning, drug-eluting stents (DES) dominated the discussions, as interventional cardiologists on the podium and in the audience debated how extensively to incorporate the new devices into their everyday practices. And, just as expectedly, enthusiasm about the clinical value of the new stents was almost evenly balanced with concerns about larger societal—read, economic--concerns.

To some degree, the timing of PCR made it an appropriate forum to recap much of the clinical trial work in DES that has taken place over the past couple of years. The days when the initial results of the RAVEL or FIM studies—both of which showed zero percent restenosis and target revascularization as a result of drug-eluting stents—took away interventionalists' breath are long gone. Compelling clinical results of DES are almost taken for granted, and news that longer-term follow-on studies from those initial studies sustain the early clinical outcomes also doesn't surprise anyone.

Debates about what the early randomized clinical trial (RCT) results didn't show never materialized. True, some speakers noted that the research focus has shifted from the original short-term measures, such as restenosis and revascularization rates, to longer-standing concerns such as the incidence of incomplete apposition, aneurysms, and delayed or persistent restenosis. And some argued that the data on specific patient sub-groups—diabetics, for example, or patients with long lesions—remain incomplete. But the formal presentations and side conversations at PCR reflected a general sense that the clinical efficacy of DES has been demonstrated and that future studies, of specific patient sub-groups or potential long-term complications, aren't likely to uncover serious problems with the technology.

Interestingly, one aspect of the shift in direction was an implicit comparison of different drug-eluting stents. The early randomized trials all focused on the sirolimus-based Cypher stent. But much of the PCR program was given over to the series of recent TAXUS studies sponsored by Boston Scientific Corp. around its paclitaxel stent, as well as reports of early RCT data sponsored by other cardiovascular device companies. (One audience-response Q&A revealed that 43% of interventionalists polled believed that sirolimus and paclitaxel are clinically equivalent; 39% believe they aren't and 18% said they didn't know.)

As such studies multiply, they further push DES clinical trials away from purely clinical considerations to practical concerns. Indeed, one interventionalist noted that the TAXUS trials may be the beginning of the end; it will be rare, he said, to see DES trials in the future that compare DES efficacy to that of bare metal stents or coronary bypass surgery.

But the abundance of data hasn't, in one respect, really clarified the issue of when and whether to use DES. Even Patrick Serruys, MD, head of Rotterdam's Thoraxcenter and one of the strongest advocates for widespread adoption of DES, conceded that "the choice or rationale for selection of drug-eluting stents has put doctors in a difficult position."

Cost is one—perhaps the major—consideration, particularly in Europe; notwithstanding reports of some deal-cutting at hospitals, particularly in Germany, DES are nominally priced at around $2,000 in Europe, several times that of bare metal stents. And tied to the money issue is efficiency: true, drug-eluting stents can dramatically reduce, if not eliminate, restenosis. But does the relative benefit—eliminating the risk of revascularization in, at most, one-fifth of all patients—justify an across-the-board adoption of the technology?

Clearly, the practical realities of DES adoption, reflected by the PCR program, is the issue of the moment. Given that study after study has demonstrated convincingly that physicians can reduce revascularization from 15% to 2%, at worst, should the decision to implant a drug-eluting stent be driven solely by clinical considerations or is it acceptable—even appropriate—to allow economic concerns to intrude? Phrased differently, with the clinical evidence so compelling and prices so high, how can doctors afford—or afford not—to adopt DES widely?

For his part, Serruys has chosen to use drug-eluting stents wherever possible. But he got around potential cost problems by, in effect, turning The Thoraxcenter into a huge research project, through the creation of a large registry of early DES experience. Few physicians face the same option.

Thus one debate the data raises is, if a physician can't adopt drug-eluting stents for all of his or her patients, how does he make the choice when to use them? Interestingly, interventionalists at PCR came down in opposing camps on this real-world question. Some argued that until more data is in, the best way to triage or rationalize DES utilization is to restrict use only to those patient sub-groups for whom the early clinical data has demonstrated efficacy. Others argued, instead, that if drug-eluting stents do represent a compelling clinical benefit, physicians should begin adoption with those patients at highest risk for restenosis, whether or not the RCT to date have proven efficacy for those patients.

That assumes that physicians will have to, for cost reasons, make a choice. But DES advocates argue that physicians shouldn't have to make a choice. For one thing, they note, reimbursement has been widely, if not universally, established. At one PCR session, Martin Leon, MD, of NY's Lenox Hill Hospital, who was principal investigator in the SIRIUS trial, argued that with CMS willing to pay for 1.4 stents per PCI, US physicians who don't use drug-eluting stents may actually be costing their facilities money—and unnecessarily depriving patients of the best therapeutic option available.

Moreover, DES advocates go on to argue more broadly that by reducing the number of re-interventions by 20% or so, the new stents represent the ultimate in cost-benefit trade-off. Data presented by Serruys showed that Rotterdam's overall patient costs for drug-eluting stents were around 10,000 euros versus 13, 500 euros for bare metal stents. An economic analysis of 156 patients from the SIRIUS trial suggested similar savings, from just over $18,000 to treat patients with DES to slightly more than $21,000 to treat patients with bare metal stents.

But such data requires a calculation for interventions not done—and implies that hospitals are saving money on procedures they may not have performed. For many physicians and hospitals, the sheer price increase of DES represents an increase in per-procedure costs.

Such analyses aside, the practical realities of early adoption seem to suggest that physicians in Europe are being cautious. Officials from Johnson & Johnson 's Cordis Corp. have reported that DES utilization in the US is, if anything, ahead of projections, and many industry observers believe market penetration there will easily reach 70%. But, as reflected at several presentations at PCR, penetration rates within Europe remain far below such optimistic projections. Admittedly, Europe is a much more cost constrained market than is the US. But, noted one physician, one year after introduction, DES penetration in Europe is still only around 11%. In major markets like France (5%) and Germany (4%), it's significantly lower. Even in markets like Scandanavia (21%), Italy (14%, and the Netherlands (16%), DES penetration has made only modest progress. Said one interventionalist, "Anyone who tells you that their drug-eluting stent penetration is 90% isn't representative."