New York, NY - New York, NY - Within months of their approval, the two "next-generation" drug-eluting stents are increasingly eclipsing the Cypher and Taxus as the choice of interventionalists in the US. A survey of 41 "high-volume" interventional cardiologists conducted by JP Morgan estimates that within the first month of the Xience/Promus stent's launch, interventionalists are choosing it in 28% of cases, and they anticipate that its use will climb to 41% before the end of the year. (The Xience and Promus are identical stents, marketed separately by Abbott and Boston Scientific respectively, as part of the 2006 buyout deal.) By comparison, the survey suggests that Medtronic's Endeavor, on the market since February, is being used in 17% of cases, while Taxus stent use has declined to 27%, from 45% at the beginning of the year, and Cypher use is down to 29%, from 37% in early 2008. Survey respondents predicted that their use of both of these stents would continue to decline over the next few months.

Interventionalists who spoke with heartwire acknowledged they are already developing new habits around stent choice, even in the absence of long-term data showing how the newer devices stack up against the Cypher and Taxus for safety and efficacy.

No single person or single center has enough real experience with any of these new stents to make good strong conclusions about long-term performance and the things we really care about, like mortality or even restenosis.

"In our lab, we're seeing a complete disappearance of the Cypher and Taxus," Dr Ron Waksman (Washington Hospital Center, DC) told heartwire. "With the Taxus, I think it's because the results from SPIRIT III favored Xience over Taxus, and with the Cypher, it's a good stent, but it's first-generation and less deliverable."

"Everybody is trying [the newer stents] out and taking them out for a spin," Dr David Cohen (Saint Luke's Mid America Heart Institute, Kansas City, MO), told heartwire. "They are the new darling, and most interventionalists, myself among them, tend to be somewhat enamored of and curious about the new thing. But the challenge for us with these types of devices is that the only thing you can really honestly evaluate is how they feel in your own hands, how they deliver, and how they look. No single person or single center has enough real experience with any of these new stents to make good strong conclusions about long-term performance and the things we really care about, like mortality or even restenosis."

According to Waksman, some interventionalists tend to view the Endeavor as "DES-lite," based on the higher angiographic late loss associated with the device in the clinical trials, but also believe it may carry less risk of stent thrombosis. So far, however, there are no clear signs that this stent will indeed be associated with higher rates of restenosis or that it is, indeed, a safer stent long-term.

I do believe that the late safety story emerging with Endeavor is pretty compelling, and, when the studies are done, I do not think we'll need the long-term dual antiplatelet therapy with this device.

"People will say that in the cases when you're really worried about restenosis, you would stick to the Xience/Promus, Cypher, or Taxus, but if you're worried more about stent thrombosis or patient compliance with dual antiplatelet therapy, you would favor Endeavor; that's the tendency," Waksman said. "The perception is that the Endeavor still is the safer stent long-term, even though there are no definitive data."

Indeed, both Drs Roxana Mehran and Jeffrey Moses (both at Columbia University, New York) acknowledged they lean toward the Endeavor in patients who are older, on warfarin, or who may need to interrupt dual antiplatelet therapy.

"Certainly, when there is any issue about the antiplatelet use, I will go with an Endeavor stent. Those data seem very promising, although it's still not yet proven that it's much safer. It just seems to be looking that way," Mehran told heartwire.

Moses, likewise, said he puts the Xience/Promus "in the Cypher/Taxus category as really a potent antirestenotic device," whereas the Endeavor, he acknowledged, "I use a little differently: I do believe that the late safety story emerging with Endeavor is pretty compelling, and, when the studies are done, I do not think we'll need the long-term dual antiplatelet therapy with this device."

Not everyone agrees. Dr Stephen Ellis (Cleveland Clinic, OH) says Endeavor use there is in the "low single digits."

"When you look at the available data . . . I don't think they have a compelling story to make them sound like they are necessarily better than any of the other DES," he said. "And that's the only reason to use that stent as far as I'm concerned."

And Cohen points out that there is still another option. "Even with Endeavor, we don't have any data with less than six months of dual antiplatelet therapy, and what we're worried about is the people who are going to stop taking it in the first month or two, so I haven't tended to use Endeavor with that idea in mind," he said. "If I am really worried about compliance with dual antiplatelet therapy, I'll use a bare-metal stent."

Dr Peter Berger (Geisinger Health System, Danville, PA) says the risk of late and very late stent thrombosis continues to be one of his chief concerns, and for that reason, he's "watching the Endeavor safety data closely.

"I don't think we can be sure, and cross-trial comparisons are fraught with hazard, but there are at least some data to suggest Endeavor might possibly have a lower late thrombosis rate than other DES," he told heartwire. "It is also slightly easier to deliver than other DES, but to be honest, they all deliver well enough to make ease of delivery a nonissue in the overwhelming majority of cases."

And even for the Xience/Promus, some interventionalists are taking a leap of faith. "At least in some people's minds, since the drugs are similar, they're substituting the Xience/Promus for Cypher directly," Ellis explained. "Others are more concerned about the lack of a robust long-term data set for safety and have not made that switch, and I tend to be in that camp."

Almost everyone who spoke with heartwire praised the deliverability of the two new devices, compared with the Cypher and Taxus. "The stents that we've been using for the past five years were really frozen in time," Moses explained. "The bare-metal technology moved way ahead in terms of deliverability, so it's nice to have the combination of both back."

But with deliverability comes a new set of issues and responsibilities. A review of the FDA's Manufacturer and User Facility Device Experience Database (MAUDE) indicates that of more than 100 adverse-event reports for the Endeavor stent between January 1 and July 31, 2008, more than half include reports of dislodgement with the stent. No adverse-event reports are yet posted for the Xience/Promus, since it was only recently approved.

I heard of one or two cases of dislodgement with Endeavor elsewhere, and I also heard of one or two cases where people couldn't retrieve the balloon with the Xience, but I wouldn't [put much stock] in these reports, because I think people are oversensitive to anything when it's new.

"We've heard of both Endeavor stents and Xience/Promus stents occasionally coming off the balloon, to a greater extent than one would expect based on our experience with the other stents. We've also, in our own lab, had some issues with the Xience sticking to the balloon—very reminiscent of the Taxus experience," Ellis said. "It may be a matter of overconfidence, or just that these stents are very deliverable and it may be a matter of trying to deliver them in situations in which you wouldn't even contemplate putting a Cypher, for example. So it's hard to know how much to blame the stent, the operator, or the expectations."

Cohen, who said he had neither experienced nor heard anecdotally about stent dislodgement being a problem, said, "If it were occurring, I would probably chalk it up more to trying these stents in tougher lesions than we otherwise would than to any kind of manufacturing defects. Just like when Cypher first came out, people very zealously reported stent thromboses and those kinds of things."

And Waksman, who said he knew of a few "anecdotal cases of dislodgement," said: "I don't think it's a problem; we haven't seen anything like this in our lab. I heard of one or two cases of dislodgement with Endeavor elsewhere, and I also heard of one or two cases where people couldn't retrieve the balloon with the Xience. But I wouldn't [put much stock] in these reports, because I think people are oversensitive to anything when it's new; if something significant had come up, we would have heard about it more vocally."

Moses, who says he's not heard of any problems with either of the new stents, says he's "not aware of anyone really pushing these devices beyond where we were at the high-water mark with the previous versions." But he does point out that there are technical differences that require new skills or old skills to be remembered. "If you size these in a certain manner and then overdilate a very compliant balloon, there's a chance for edge dissection," he said by way of example. "That's nothing intrinsic to the device, it's how they're being used."

Medtronic spokesperson Daniel Beach, asked about the dislodgement issue, emphasized that despite being used preferentially over Taxus and Cypher in difficult anatomies, "the dislodgement rate with Endeavor is very low, less than one hundredth of 1%." He also pointed out that device success and procedure success rates for Endeavor were superior to those of both Taxus and Cypher in randomized clinical trials.  

"All stents are affected by dislodgement at low rates; it is well understood by physicians and arises from the unavoidable need to force stents into difficult anatomies," he said. "The MAUDE database is a valuable resource but, as the FDA has publicly commented on several occasions, it should not be used to make device comparisons. This is particularly the case when looking at a newly available product and examples of a technology that are nearing the end of their lifecycle. For example, MAUDE takes no account of the possibility that one device is being used preferentially over another in challenging patients because of design and performance advantages. Such preferential usage could result in a disparity of adverse events associated with a particular device in MAUDE precisely because of its superior performance."

While Mehran, Moses, and colleagues at Columbia are world-famous for using DES in the majority of cases, other institutions are more conservative, producing an average DES usage in the US that hovers between 60% and 65%. Waksman says his lab is even more conservative, using just 50% DES. Key factors are the need for dual-antiplatelet therapy long-term, and in some cases, cost. Several interventionalists pointed out to heartwire that while the price for all four devices is slightly lower, the price wars that many had predicted with the advent of a fourth DES have not come to pass.

Price and other factors that influence physician preferences may shift in the coming months with longer clinical-trial follow-up and registry data for the newer devices trickling in, as well as new study results comparing first- and next-generation DES. While Medtronic's 8800-patient PROTECT study and Abbott's SPIRIT IV and V trials are still under way or have yet to report results, the TCT 2008 meeting will include results from the smaller SORT-OUT III (Cypher vs Endeavor) and ZEST-AMI (Endeavor vs Cypher vs Taxus) studies.