New York, NY - In the wake of the FDA's drug-eluting stent (DES) safety hearing, interventional cardiologists are saying they found the process "reassuring" but believe the panel's conclusions will have very little influence on their day-to-day practice.

If anything, the potential impact of the hearing preceded its actual occurrence, Dr Gregory J Dehmer (Texas A&M School of Medicine, Temple), president of the Society for Cardiovascular Angiography and Interventions (SCAI), told heartwire. "Any results that might have come out of the panel in terms of a dip in DES use were already occurring before the panel meeting ever took place," Dehmer said. "Reports after the [World Congress of Cardiology 2006] meeting showed that there had been a very distinct drop, so in a sense that was the shot across the bow to interventional cardiologists that they needed—not to stop using DES, but to at least be a little bit more thoughtful about the circumstances in which DES provide the greatest benefit and the circumstances in which DES might not be any more advantageous than bare-metal stents."

Likewise, Dr Roxana Mehran (Columbia University, New York) said she was "not surprised" by anything the panel put forward. "It will perhaps decrease DES use, but not to the 20% or 30% range as is happening outside the US," she said. "I think if we do our due diligence and understand the current impact that DES have had in terms of reduction of restenosis—which is not a benign entity—I think that in the end we'll probably end up somewhere between 75% to 80% usage in those patients."

Dr Neal Kleiman (Methodist DeBakey Heart Center, Houston, TX) believes the drop will be "measurable" but not "dramatic."

"I think at least in the US people are going to be a little more cautious, but I wouldn't predict that we'll see a dramatic drop in DES use. There are patients who are going to come in and say 'I don't want one of those time bombs.' If they're adamant, you can say, look, you have to trust my judgment, but it's likely operators are going to have to take that into consideration. Patients are aware of this issue and you have to respect their wishes, even if you don't agree with them."

Many of the cardiologists interviewed by heartwire—all of whom also attended and/or presented data at the meeting—also emphasized that they thought people who had already received DES or who are scheduled to undergo PCI should feel more confident about DES safety in the aftermath of the hearing.

"I think overall, this news should be reassuring to patients," Dr Laura Mauri (Harvard Clinical Research Institute, Boston, MA) told heartwire. "The diverse body of observational data could be summarized as: both bare-metal and drug-eluting stents have higher risks when used in higher-risk lesions and patients. More work is definitely needed in several areas: achieving recommended dual antiplatelet therapy in all patients with DES through patient and physician education and more rigorous studies of currently off-label indications, particularly left main and bifurcation lesion treatment."

But most experts who spoke with heartwire following the meeting agreed that in the absence of any strong warnings or specific contraindications, the panel's recommendations to the FDA more or less give practicing interventionalists license to continue doing whatever they want to do and to construe the data as they choose.

"It's interesting how people interpret things differently," Dr David Williams (Rhode Island Hospital, Providence) observed. "I myself didn't see a lot of recommendations, quite frankly, coming out of that group in a formal way."

No matter how you sliced and diced it, and no matter whose stent it was, there was no excess death and MI from the DES and there was sustained benefit.

The panel was very diverse in its views, Williams noted, and there was a lack of consensus on most of the issues discussed. "I think overall the process was reassuring for physicians and patients, and I think that's the bottom line. . . . I also had a sense that the data presented from the four-year follow-up of randomized patients were solid and rigorous, and no matter how you sliced and diced it, and no matter whose stent it was, there was no excess death or MI from the stents and there was sustained benefit."

The upshot, said Mehran, is that physicians should feel confident using DES, as long as they are weighing the pros and cons carefully. "I think this really does put the clinician back in the position of using their clinical acumen, assessing patients as a whole, taking a good history and physical exam, and making sure patients are going to be able to take the antiplatelet regimen that's been recommended out to one year."

The panel's recommendations that dual antiplatelet therapy should be extended to 12 months packed little punch for interventionalists, who for the most part have already been doing this and seemed to believe that 12 months is already being advocated by professional guidelines. In fact, the current ACC/AHA/SCAI guidelines advise following device labeling and "ideally" extending dual antiplatelet therapy to one year. Williams, who coauthored the current guidelines, confirmed that the word "ideally" would be dropped the next time US guidelines are issued. As well, Williams believes the guidelines should also remind physicians of the necessity of exploring "ahead of time" whether patients will be able to take clopidogrel long term and be compliant.

Any remaining uncertainty over dual antiplatelet therapy seemed to stem not from whether a shorter duration of clopidogrel might be sufficient but rather whether extending it is ill-advised.

"Although there are some that would favor extending the recommendations for clopidogrel to beyond one year, the available data are still imprecise," Dr David Kong (Duke University, Durham, NC) commented. "The committee went as far as the data could support them. Indeed, the panel meeting helped regulators, academicians, and industry evaluate not only what we know, but also what we don't know, and certainly highlighted the need for additional trials in this area."

"I think it's just common sense," Kleiman told heartwire. "To me the biggest issue is whether to put a DES in or not, from day one. And whether to stop clopidogrel if someone is tolerating it well, when you see them a year later, is a much less crucial decision."

An interesting tidbit emerged during the hearing from trial sponsors—one that very few cardiologists seemed to have previously been aware of. This was that although the original labeling for the Cypher and Taxus stents was based on the study protocols stipulating three and six months of dual antiplatelet therapy, respectively, a substantial proportion of participants in both trials actually received dual antiplatelet therapy beyond these time points.

"While these regimens may be acceptable for certain low-risk patients, it is difficult to generalize . . . to the broader population," Kong commented. "Accordingly, I think it was wise to mandate 12 months as a minimum duration for dual antiplatelet therapy. Although there may be an incremental bleeding risk, there have been sufficient trials of yearlong clopidogrel therapy after PCI to suggest that the potential benefits exceed the potential risks."

Cardiologists who spoke with heartwire uniformly praised the FDA for putting together such an unprecedented and comprehensive collection of DES studies for review, even if the sheer quantity and varying quality of the information may have obscured as much as it illuminated.

No matter what the recommendations are, the FDA did a service and I'm hopeful that it will help dampen some of the hysteria that has really taken off over the use and hazards of DES.

"I think the FDA should be commended for getting these results out in the sunlight for everybody to see," Dehmer said. "No matter what the recommendations are, the FDA did a service, and I'm hopeful that it will help dampen some of the hysteria that has really taken off over the use and hazards of DES."

But one of the lingering uncertainties from the meeting is how long, if at all, approval of next-generation devices might be delayed. Several people interviewed by heartwire expressed the fear that up-and-coming DES may have to pay for the sins of their predecessors. Still others suggested this was completely appropriate and necessary.

Dr Sanjay Kaul (Cedars Sinai Medical Center, Los Angeles, CA), who spoke on the second day of the FDA hearing, argued persuasively for longer, more robust trials, with emphasis on hard clinical outcomes. "Over the past 24 hours, we've all seen post hoc science being elevated to a much higher level: whatever happened to the hypothesis driving the data and not the other way around?" he asked. "If nothing else, what we have learned is that we need larger and longer preapproval randomized controlled trials that include a broad spectrum of patients more representative of the real world, that assess hard clinical end points such as all-cause death and Q-wave MI, and that are adequately powered to do so."

But Dr Patrick Serruys (Erasmus Medical Center, Rotterdam, the Netherlands), in an interview with heartwire, underscored the need to move forward. "The only thing I'm afraid of is that because we did not foresee all the complications of this new technology, regulators will slow down the technology that is coming to fix and mend the deficiencies of the first generation. The European regulators are now taking a very difficult, fanatical position. We are coming with biodegradable coating, we are coming with coating on only one side of the stent and new drugs that are not antiproliferative or anti-inflammatory, but now the regulators are wanting to have five-year trials with hard clinical outcomes."

Manufacturers of the approved devices, however, must be sighing in relief. In a display of confidence and transparency, both Boston Scientific and Johnson & Johnson/Cordis have posted copies of their presentations to the FDA on the internet. So, however, have surgeons whose presentations proposed that there is a considerable survival advantage associated with CABG over DES in multivessel disease. These have been posted on the website of the Society of Thoracic Surgeons.