Medical Device Daily Washington Editor

WASHINGTON — The 2007 conference edition of Transcatheter Cardiovascular Therapeutics kicked off this past Saturday, and given the fireworks in 2006, some might have expected more controversy regarding drug-eluting stents (DES). But updates to existing registry studies seem to have turned the tide, modifying the grim sobriety that followed the exuberance accompanying initial DES roll-out.

At least one participant remarked that while the media fueled the hysteria over negative DES outcomes, excessive rhetoric by physicians also heightened patient fears following the mixed safety data for DES compared to bare-metal stents (BMS). Another presenter offered data that showed that DES is more cost-effective than coronary artery bypass grafts (CABG) — at least as far as the Medicare budget is concerned.

Gregg Stone, MD, director of cardiovascular research at New York-Presbyterian Hospital/Columbia University Medical Center (New York) and a board member of the Cardiovascular Research Foundation (CRF; New York), the sponsor of TCT 2007, termed 2007 “a very interesting year for percutaneous interventions.” He said that for some, the question was “whether we should be doing percutaneous interventions at all.”

“There’s an old saying,” Stone said, “that if everything seems to be going well,” something is probably wrong, and he blamed the DES “firestorm” on analyses such as the Bern-Rotterdam study which showed serious adverse events but included no control group.

Stone noted that the meta-analysis of Eduardo Camenzind, MD, of the University of Geneva — presented in the now-famous Barcelona session in 2006 — was based on abstracts and included no analysis of original data. Shortly after, others started trying to link DES with prostate and gastro-intestinal cancers and emphysema.

“Then we started being bombarded with pictures” regarding various effects, including stent fracture. “And boy, did the media pick up on this,” he said, adding that interventionists as a group “were running for cover.”

He said the SCAAR study showed as much as a 30% increase in mortality risk over plain stents, but this did not reflect “outcomes we were seeing in our own experiences.”

Data from several manufacturers’ randomized, controlled trials showed “a slight excess in late stent thrombosis [LST]... but this did not lead to” mortality or infarction, “but [to] a dramatic decrease in re-hospitalization and re-occlusion.”

Martin Leon, MD, founder and chairman emeritus of CRF and a professor of medicine at Columbia University Medical Center (New York), was one of the main early cheerleaders for DES, and he accused the media of fueling the fears concerning DES that greatly reduced their use.

Return data from clinical use patterns showed, he said, an “unprecedented decline in PCI procedures in the last year,” a reduction of as much as 25% in some practices. He said that DES penetration is down to 62%, a drop of more than 20%, and he noted a “slight decline in Europe, but not very much,” with varied penetration in EU nations.

Heightened concerns about dual antiplatelet therapy (DAPT) have also driven the reluctance to employ DES, Leon said. “Safety is the dominant issue” for physicians, but late stent thrombosis “is generally appreciated as an event that has become infused in most clinical practices.

“In the next few years, projections are for flat growth [for DES] in the U.S., but robust growth outside the U.S.,” he said. The best years for DES in the U.S. were 2005 and 2006, and he said that overall stent use, despite the controversies, will increase 193% from early in the century to 2010.

“Price erosion will continue with marked geographic disparities,” Leon predicted, referring to data from the financial services firm Morgan Stanley (New York). He also cited Morgan Stanley data indicating that by the end of the decade, the average price of DES in the U.S. will be less than $2,000.

Prices outside the U.S. are already lower, and Leon said that the competition is heating up so as to lower prices further. And he admitted to having “no clear idea of who will be the winner.”

But he said there is no need to panic, given the huge opportunity. “This is still a $5.5 billion dollar market,” he said.

“Safety considerations will likely redirect DES technology,” and the emphasis will be on new platforms such as bioresorbable stent frames and new drugs, Leon said, adding that three of four doctors see bioresorbability as the key. “There are now many non-polymer platforms... and many others” to control luminal growth. But it is “not entirely clear,” he said, whether bioresorbables will dominate the sector, given the advent of microstents and other developments.

Leon characterized the past year as “a climate of calamity in the once-burgeoning U.S. market.”

Since the December 2006 FDA panel, “preclinical animal studies are emphasized... with [more] detailed review of all safety characteristics.” Now patient outcome endpoints, not just lesion endpoints, are of interest, Leon said, adding that Medtronic had to go to an advisory panel for the Endeavor despite data from studies that encompassed more than 25,000 patients.

In the current environment, he said, developing a new stent “will cost as much at least a $100 million” by the time it hits the market. Still, Leon said that the problem was, in part, the “unbridled enthusiasm” that initially met DES technology, and has now morphed into “realistic applications” aided by new technologies.

David Cohen, MD, director of cardiovascular research for Saint Luke’s Mid-America Heart Institute (Kansas City, Missouri), presented cost-effectiveness data concerning DES compared to coronary artery bypass grafting (CABG), numbers that did not send chills through the room. He said that the analysis was decisive in favor of the new technology over CABG.

Using a 5% random sample of records from cases reported in 2001 and 2004, representing about 30,000 patients, Cohen reported that “total expenditures fell by $1,000” with the use of DES compared to CABG, partly because of lower follow-up costs. On the other hand, during that period the cost of CABG also dropped by about $418.

Risk-adjusted clinical outcomes favored DES over CABG for myocardial infarction, death, and restenosis, Cohen said.

Is there any down side to the use of DES in lieu of CABG? For one thing, DAPT costs are greater in the case of stents, but “despite the higher upfront cost, aggregate spending... actually decreased by more than $1,900 a year,” even with up to a year of DAPT.

“The introduction of DES was associated with both improved outcomes and lower cost,” Cohen concluded.