Bare-Metal, Drug-Eluting, and Bioresorbable Stents in Context

Gurpreet S Sandhu, MD, PhD; Malcolm R Bell, MD; Rajiv Gulati, MD


February 22, 2017

Editorial Collaboration

Medscape &

This feature requires the newest version of Flash. You can download it here.

Rajiv Gulati, MD, PhD: Greetings, I am Rajiv Gulati, interventional cardiologist at Mayo Clinic in Rochester, Minnesota, and today we'll be discussing what's new in bare-metal and drug-eluting stents. I'm joined today by my colleagues, Dr Gurpreet Sandhu, director of the cath lab at Mayo, and Dr Malcolm Bell, director of the Ischemic Heart Disease Program. Welcome, gentlemen.

Gurpreet Sandhu, MD, PhD: Thank you, Rajiv.

Malcolm Bell, MD: Thank you.

NORSTENT: Overview

Dr Gulati: Malcolm, maybe I can start with you. Why don't we start with [the Norwegian Coronary Stent Trial] NORSTENT. Tell us what the study was and the headline findings.

Dr Bell: NORSTENT was recently presented and published.[1,2] It is important, though, to understand the historical context of this trial, remembering that drug-eluting stents [DES] were developed to overcome the failings of bare-metal stents over many years. [But] early on, there was a concern about added risk with drug-eluting stents—even though they reduced restenosis—because of the issue of stent thrombosis.

Dr Gulati: This is the first-generation DES.

Dr Bell: First-generation drug-eluting stents. We're talking about the Cypher (Cordis) and the Taxus (Boston Scientific) stents, in particular.

Over time, with second-generation drug-eluting stents, it became apparent from a number of meta-analyses that perhaps these stents were actually safer than bare-metal stents.

It is not clear that that message was heard by everyone in the field, but recent guidelines have suggested that drug-eluting stents are superior to bare-metal stents and that [the] safety issue is no longer important.[1,2]

Some of those analyses actually suggested there was a decrease in myocardial infarction (MI) and mortality with current drug-eluting stents, and that's always been a little difficult to fathom.

That was the background. NORSTENT was a large, well-conducted Norwegian study. It enrolled probably 60% or more of all of the [percutaneous coronary intervention] PCI procedures done in Norway from 2008 to 2011. [Patients] were randomized to bare-metal stents or drug-eluting stents.

The [trial] took all-comers. That's important because it reflects our current practice—using stents that we're using today. It's a very important study, and I think they need to be congratulated that they did a randomized study in every stent center in Norway. It is the largest bare-metal stent vs drug-eluting stent study ever performed, in over 9000 patients.

Getting back to your original question, the headline news was that the primary end point—and this is important for everyone to understand—showed that MI and mortality were equivalent.

Some people would be surprised by that, but we shouldn't be because we've never shown that DES have improved survival compared with bare-metal stents, and why would they necessarily decrease MI? But, in particular, the survival question was very clear from this study.

The secondary end points were target-lesion revascularization [TLR] and stent thrombosis, and it was clear that drug-eluting stents were superior in both end points compared with bare-metal stents. It showed that second-generation DES perform better than bare-metal stents. In particular, the rate of stent thrombosis was reduced and revascularization was reduced, which is exactly why these stents were developed in the first place. This is really good news for all of us who are using the second-generation drug-eluting stents.

Dr Gulati: Very good. Gurpreet, the primary end point was moot, it was negative, but the rates of TLR are lower with the second-generation drug-eluting stents. [Is that] clinically meaningful, economically meaningful?

Dr Sandhu: This is clinically meaningful because, as you know, the absolute reduction in TLR was 5% for the drug-eluting stents (5.3% vs 10.3% for bare-metal stents). That is a substantial difference and goes in line with what we know about drug-eluting stents and why they were designed.

Similarly, as Malcolm mentioned, the stent-thrombosis rates were about 0.8% for the drug-eluting stents vs 1.2% for the bare-metal. So, both were equally good, but reassuring results overall.

Dr Gulati: Let me ask you one more [question] on this study, Malcolm. Patients with diabetes were under-represented in this trial, how does that affect the results?

Dr Bell: It was all-comers, and there were very few exclusion criteria. If you had a prior stent, you weren't allowed to be in the study and a few other exclusion criteria that would make sense, and the typical breakdown of patients: STEMI, non-STEMI, unstable angina, stable angina. About 12% of the study population had diabetes, which is at least half of what we typically see in these stent trials. I think we have to be a little more careful with interpretation, although there was no signal that one was doing significantly better in one vs the other.

Dr Gulati: Do you think they were underrepresented because they weren't randomized—the clinicians having concern about randomizing diabetics to bare-metal stents?

Dr Bell: I don't think so. That wasn't apparent to me. The other thing was that this was a relatively younger age group. As I said, it enrolled a lot of people undergoing stent procedures in Norway during that time. Yet the median age was a little lower than what we might typically see. But your question is important, because drug-eluting stents—at least in the first-generation studies—did seem to perform much better in diabetics compared with bare-metal stents.

There's one other thing I think that will come out is that drug-eluting stents were introduced about 13 years ago, and we tend to keep comparing drug-eluting stents that we're currently using with the old bare-metal stents. But we have to remember: Bare-metal stent technology has improved as well. These bare-metal stents—as we say about the second-generation drug-eluting stents—are "not your grandfather's" bare-metal stents. These are different alloys, thinner struts and, in fact, many people may be surprised at how well bare-metal stents actually did in this study. Yet drug-eluting stents still outperformed them with respect to the secondary end point.

Dr Gulati: The stent-thrombosis rate, though, was statistically significantly lower with the drug-eluting stents, which I think solidifies what we've learned from some of the meta-analyses—fascinating findings.

Any thoughts, Gurpreet, as to why the current-generation [drug-eluting stents] may have lower late–stent-thrombosis rates than the bare-metal stents?

Dr Sandhu: Several improvements have occurred over the years. The first is strut thickness. The original Cypher stents had pretty thick struts. There was also some risk of the polymer fracturing and causing stent thrombosis. That has pretty much gone away. The current-generation drug-eluting stents and bare-metal stents, like Malcolm said, are a completely different platform: lower-profile, thinner struts, and even the quality of the polymers is better.

Dr Gulati: With regard to stent thrombosis, it may be worth pointing out that in the NORSTENT study, both the bare-metal- and drug-eluting-stent groups received 9 months of dual antiplatelet therapy. When we think about bare-metal-stent utilization in the US, it is typically [done] to abbreviate the duration of antiplatelet therapy. Any comments on that?

Dr Bell: That's a great point. We have to be very cautious in our recommendation of shortening the dual antiplatelet therapy for bare-metal stents with the belief that we're going to reduce the rate of any event if we put a bare-metal stent in vs a drug-eluting stent. You're absolutely right: We have to be very careful in extrapolating to say that we could put a bare-metal stent in and give a very abbreviated course of dual antiplatelet therapy.

Again, what's important for us to remember for the finding is that the stent-thrombosis rate was actually very low in both groups. They've analyzed at a point in time when the technology has changed significantly for both stents. Survival wasn't any different.

Certainly, meta-analyses prior to the study suggested that we shouldn't underestimate the benefit of putting [in] a drug-eluting stent and that there probably isn't an up-front risk of stent thrombosis exceeding what it would be for bare-metal stent.

Dr Gulati: That's very helpful. Any role for bare-metal stent in your practice nowadays with the NORSTENT study? Which patients might you expect to use bare-metal stents in?

Dr Bell: In general, most patients should be considered for drug-eluting stents. NORSTENT shows us that there's no downside to putting a drug-eluting stent in. Furthermore, we've had recent data and guidelines supporting shorter duration of dual antiplatelet therapy—3 to 6 months, particularly for patients with stable angina.

But the patients who you might consider a bare-metal stent: if cost was an issue (that's not usually in issue in this country) or [if he or she has] very big vessel where we may need to put a 5-mm bare-metal stent in (and the incidence of restenosis there is very low).[3]

The question of the patient who is at risk of bleeding is still open. As you pointed out, bare-metal stents in this study were accompanied by 9 months of dual antiplatelet therapy [DAPT]. So, we don't know whether, in this type of population with these stents, whether each stent would perform the same—particularly in terms of safety—with shortened dual antiplatelet therapy.


Dr Gulati: Perhaps we can move onto another study—the patients with high bleeding risk and potential to reduce DAPT duration. Gurpreet, do you want to comment on the LEADERS FREE study? Give us the headline news and the design?

Dr Sandhu: The LEADERS FREE study was biolimus A9 (or umirolimus) [stent; BioFreedom, Biosensors] vs a bare-metal stent, and the patients received 30 days of dual antiplatelet therapy.[4] These stents are not available in the US, and they are also polymer-free, so it was drug on the metal vs bare-metal and about 1200 patients in each arm.

The results were fairly in line with what we know about drug-eluting stents versus bare-metal stents: about 5% vs 10% target-lesion revascularization. But there was something interesting: Stent thrombosis rates in both arms were about 2%. Maybe this is something, Malcolm, that you could comment on.

Dr Bell: It is a higher-risk population, and we still don't know the minimum duration of dual antiplatelet therapy, but these are complicated patients. There are all sorts of reasons they may have a higher risk of stent thrombosis.

Dr Gulati: These, specifically, were higher-bleeding-risk patients. They were elderly. They had other risk factors.

Dr Bell: Right, and they may need to have surgery, so there's something else about these patients. We know that, yes, they're at high risk of bleeding, and that's a problem in itself. And there is slightly higher risk of stent thrombosis, but it is hard to tease out what comes first. We don't know the circumstances, from what has been published, on stent thromboses.[1,2] Again, it tells us that we don't have to put bare-metal stents into these patients, necessarily. Patients who got the drug-eluting stents still did better.

Dr Sandhu: Is there a fine line between 3 months of DAPT vs pushing it down to 1 month for a drug-eluting stent?

Dr Bell: That remains to be seen, it really does.

Bioresorbable Scaffolds: Red Flags

Dr Gulati: We discussed the NORSTENT trial, the bare-metal versus drug-eluting, and we've alluded now to the LEADERS FREE study. Why don't we move onto bioresorbable scaffolds, the hot topic of the day with excitement for the future. Gurpreet, do you want to comment on recent findings that presented at the Transcatheter Cardiovascular Therapeutics (TCT) meeting in 2016?

Dr Sandhu: At TCT, the main discussion was the 3-year data on the Absorb stent (Abbott Vascular).

Dr Gulati: The ABSORB II trial, 3-year follow-up.[5]

Dr Sandhu: The one slight red flag there that raised concern was the late–stent-thrombosis rates with these. There were about six patients who developed late stent thrombosis out of about 300+ patients. That was concerning because in the control arm, which was the Xience (Abbott Vascular) drug-eluting stent, there was no late-stent thrombosis.

Dr Gulati: Malcolm, any comments on those findings? They have not been published yet, as far as I understand.

Dr Bell: It is a promise, isn't it? Intuitively, all of us would love to walk in and say, "If I have a stent that dissolves away and there's no evidence of it being there in 1, 2, or 3 years, then that would be wonderful." Although these trials are meeting their primary end point, there is this worrying signal of higher rates of later-stent thrombosis, which would throw the whole duration of dual antiplatelet therapy into confusion. We don't know the answer to that.

We know there are some issues in terms of deliverability. Are we choosing the right size of stent? When [the stent] was FDA approved, they had data showing a signal of these later events being more frequent with the bioabsorbable vascular scaffold, but these may be only in the smaller vessels. We have to be careful there.

One of the promises was that this would maintain or at least restore vasomotor function, whereas you generally wouldn't with a bare-metal stent. With a metal scaffold, of course, that vessel isn't going to vasoconstrict or vasodilate. Interestingly, the ABSORB II trial did not show a difference in vasomotion, and that's a little disappointing. I think there are going to be a lot of challenges for us and our patients trying to choose who will want these stents and whom should we put these in.

Dr Gulati: Just to play devil's advocate, there have been concerns or questions about methodology. We've learned from the earlier ABSORB studies that deployment matters, technique matters. And that has the potential to influence long-term outcomes, method of assaying, vasomotion—there's multiple different ways.[6] Perhaps as we see data come out into the public domain, we'll be able to tease out nuances of the trial and how methodology may have affected long-term outcomes.

Dr Bell: That's true, and it goes back to early drug-eluting-stent days. We got a little lazy in terms of technique putting these in. Again, we haven't used these bioresorbable stents in the United States for very long at all, so we don't have a vast experience. Implantation technique is going to be absolutely critical. We cannot afford to get sloppy with these stents.

More long-term data will come out with the ABSORB IV trial, and we're hopeful that these will be reassuring. But at the moment, there are some worrying signals—not enough to say that we should never use them. We've got to keep an open mind. These are first-generation devices, but I'm not sure that we're going to see second-generation absorbable scaffolds that will look very different from this any time soon. There may be some other thoughts that Gurpreet has on other types of resorbable "stents." We're talking about an absorbable scaffold, but there are absorbable polymers, so this can get very confusing for the average person who's not dealing with these stents.

Dr Sandhu: At this time, this is a first-generation bioabsorbable stent. The struts are pretty bulky; deployment technique needs to be absolutely perfect. One thing we need to remember is it doesn't disappear within a year. There are fragments that may take up to 2 years or 3 years to disappear. Those could still be thrombogenic. And it doesn't expand the same way as a metal stent—where you inflate it with a balloon and it stays open. Here, it is a stepwise, careful dilatation, so mechanically it is different.

Dr Gulati: That's a very fair point. This is first-generation [bioresorbable stent] technology compared with what you both have already described as the best-in-class second-generation, super-outcomes [drug-eluting stent] that we have. Perhaps moving forward with more data, we'll see things change.

Dr Bell: We need to be very careful in our patient selection. We're about to introduce these into our own practice and will have to [identify ideal patient candidates]. Obviously, there are some lesion specifics that we may want to avoid. It may be that, in an elderly patient with comorbidities, the benefit of a resorbable stent is not as great as it might be for a younger person. I don't know how we're going to tease that out. I don't think you suddenly change your practice and start putting bioabsorbable vascular stents into everyone.

Dr Gulati: Gentlemen, thank you for your important insights today about new developments in stent technology and stent comparisons, and thank you for joining us on on Medscape.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.