Embers Still Smoldering From the 2006 ESC Firestorm, As Experts Mull DES Safety and Efficacy

Shelley Wood

August 30, 2009

August 30, 2009 (Barcelona, Spain) — Exactly three years after the drug-eluting-stent (DES) "firestorm" ignited at the World Congress of Cardiology 2006 here in Barcelona, experts in the field are doing their best to gingerly stamp out some of the still-smoldering coals. But the topic of late stent-thrombosis risk with DES still produces sparks. In a session entitled "Is it time to turn the page on Barcelona 2006?" investigators for some of the biggest trials in this contentious area--including Dr Edoardo Camenzind (University Hospital Geneva, Switzerland), whose presentation that year became emblematic of the controversy and subsequent dramatic fall-off in DES usage--debated the evidence and tried--with mixed success--to find some common ground.

The session took place on the opening day of the European Society of Cardiology 2009 Congress.

Camenzind led off by reviewing original and follow-up published papers and presentations from BASKET LATE, RAVEL, SCAAR, and others. Camenzind emphasized that the bulk of the evidence points to an enduring risk of late stent thrombosis of 0.5% to 0.7% after one year and out to at least five years with DES. Several published papers of randomized controlled trials, he notes, have reported numerical differences in stent-thrombosis rates for DES and bare-metal stents but have failed to report p values, adding to the lingering uncertainty. On the flip side, most of the reassuring information on the lack of any clinical significance of a real or hypothetical increased stent-thrombosis risk with DES has come from registry data, Camenzind noted. "Registry data should remain hypothesis generating. . . . We have to keep in mind that the level of evidence for registries is B or even C."

As such, Camenzind concluded, "The doubt that total death and MI . . . have a higher incidence in potent DES, as compared with bare-metal stents, cannot in my view be definitively dissipated since Barcelona 2006."

Moreover, seemingly inconsistent or incomplete papers have complicated matters. "The reality has made professional cardiologists, regulatory bodies, and even patients confused, insecure, and uncertain about the available information," he said.

Camenzind's "practical advice" to physicians was to use DES that allow for vascular healing. "Ask first if you, yourself, would like to have one of the stents you're implanting," he said. "And your approach to dual antiplatelet therapy should be [to use it] until complete healing of the [vessel wall has occurred]. And last, resist short-term distractions and stick with medical evidence."

What's Clear to All?

Camenzind's less sanguine review of DES contrasted sharply, however, with that of Dr Adnan Kastrati (Deutsches Herzzentrum, Munich, Germany), who followed with a review of the randomized clinical trials of DES, opening with the bold statement: "It's clear to all that DES are a very effective therapy."

Kastrati showed data pointing to the clear reductions in repeat revascularization for DES across different DES and across different subsets of patients, including patients with diabetes and AMI.

"The evidence generated since Barcelona 2006 [suggests that] DES are the most successful therapy to date for the prevention of restenosis, and the difference found between the different stent types should serve as an incentive for improving this technology," he concluded. "Based on recent evidence, there are good reasons for us to believe that the benefit of DES in terms of restenosis is not achieved at the expense of compromised safety and for Dr Camenzind to repent his three-year old assertions."

But Kastrati, like Camenzind, emphasized that "all DES are not equal," pointing to findings from the recent ZEST results, which showed the Endeavor and Cypher stents to be superior to the Taxus in an all-comers randomized trial. And while Camenzind in his talk referred to a "transitional solution," referring to the promise of up-and-coming DES, Kastrati cautioned that newer doesn't always mean better, pointing to disappointing results of devices like the COSTAR and the GENOUS. "Not all new technologies are efficacious and safe," he said.

Asked why, if he thinks there is "no problem" with even the more potent DES currently available, he still believes that new stents in the pipeline are important, Kastrati acknowledged: "I think that you can still improve this technology and you cannot stop companies from developing the technology. The fact that many of these devices have a permanent polymer there, for life, is some cause for concern."

SCAAR Scare No More

In a third presentation, Dr Stefan James (Uppsala Clinical Research Centre, Sweden) sided closer to Kastrati, concluding that it was indeed time to turn the page on the rampant concerns of 2006. James and his Swedish coinvestigators contributed significantly to DES disquiet late in 2006 with their now-infamous "SCAAR scare." Registry data from Sweden presented during a 2006 FDA hearing indicated that rates of death, MI, and death/MI after six months were significantly higher among DES-treated patients than among bare-metal-stent-treated patients over 2.5 years of follow-up and after adjustment for background characteristics.

But showing new SCAAR data here on almost 61 000 patients treated with stents between 2003 and 2006, James declared the "SCAAR scare" is no more. At up to five years, rates of death/MI after the one-year mark (the time at which most patients stopped taking clopidogrel) were no different between patients with DES and those with bare-metal stents.

The Achilles heel for DES, however, remains stent thrombosis, James added. Emphasizing that the findings are only hypothesis-generating, based on observational data, James showed SCAAR data indicating that the increased risk of stent thrombosis seen back in 2006 remains in 2009, roughly double that seen in bare-metal stents over the long term. But again showing new Swedish data, James pointed out that the stent-thrombosis rate does seem to differ for different DES, and indeed, for different bare-metal stents.

In a press conference, James concluded: "There was an increased risk of stent thrombosis, but overall we don't need to worry about it, because the mortality is not increased. . . . So we don't need to be worried, but we need to be aware of it and we need to do everything we can to avoid using DES in patients who are not able to take dual antiplatelet therapy and in those patients in whom we do not know if they will be able to take dual antiplatelet therapy in the future."

A Wake-Up Call Was Needed

Speaking with heartwire following their presentations, Camenzind and Kastrati seemed to agree on some points, but not on others. Both acknowledged the flaws of registry data, and both emphasized that DES safety and efficacy differs by type of stent. But Camenzind, while refusing to give the "brand names" of the DES he will use, says "there is no space" in his practice for "very potent DES." Like James, Camenzind said that he believes appropriate usage of DES is likely around 35% of total stent use. And he advised that when such "potent" DES are used, "you have to be aware that that is likely going to have to be combined with lifelong dual antiplatelet therapy."

Kastrati, however, said he "cannot agree" with Camenzind's conclusions, saying he continues to use DES in 100% of patients (in large part because many are participating in DES studies).

James, for his part, stressed that despite the confusion and controversy, the 2006 "firestorm" served an important purpose. "A wake-up call was needed: all of us interventional cardiologists were overly enthusiastic--we thought that DES would solve everything and we started to stent patients we never should have stented," he told a press conference. "We didn't do our job well before 2006, so it was important that we got this warning signal, to get us thinking about how to improve our techniques, our antiplatelet therapy, and our selection of patients to get it right."

Others who spoke with heartwire said they are, on the whole, reassured by the outpouring of research since 2006. Dr Marco Valgimigli (University of Ferrara, Italy) said he was "much relieved" by the data. Likewise, Dr Anthony H Gershlick (University Hospitals of Leicester, UK) told heartwire : "I think what happened in 2006 led to a lot more data, and those data are relatively reassuring. There probably still is an issue of late stent thrombosis, but it's small, and it probably doesn’t translate into clinical differences. The real issue is how long you continue dual antiplatelet therapy for, and there's nothing I heard today that would change what I do at the moment, which is to give one year of dual antiplatelet therapy and continue it longer for certain patient subsets."

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