Absorbing the ABSORB II BVS Data, and More TCT Takeaways

; Sunil V. Rao, MD


November 09, 2016

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Robert A. Harrington, MD: Hi. I am Bob Harrington from Stanford University. I am here at the Transcatheter Cardiovascular Therapeutics (TCT) 2016 meeting in Washington, DC. It is a real pleasure on the first day of the meeting—technically, the second day of the meeting—to be with my friend and longtime colleague Sunil Rao from Duke. Sunil is the chief of cardiology at the Durham VA Medical Center, professor of medicine, and a senior investigator with the Duke Clinic Research Institute. Sunil, thanks for joining me.

Sunil V. Rao, MD: Thanks for having me, Bob.

Dr Harrington: Amazing first day at the TCT. We have seen a lot of interesting trial results. Given your cath lab presence, let's focus on two of the issues and come back to [a topic] that is really important to you, which is femoral vs radial access. Two trials presented today were the long-term follow-up of ABSORB II,[1] which is the bioresorbable stent or scaffold, and an imaging study that compared optical coherence tomography (OCT), intravascular ultrasound (IVUS), and routine angiography for stent expansion. Let's cover ABSORB II first.

ABSORB and the Resurgence of Stents

Dr Rao: Okay. Fascinating, right? Stents are interesting again. We had a period of time in interventional cardiology when we thought that we had everything solved; there was a lot of focus on structural heart disease. Now, with the Norwegian Coronary Stent Trial (NORSTENT) data[2] and with the availability of bioresorbable vascular scaffolds, we are talking about stents again. This is an interesting study. Just to remind folks, the Absorb GT1 Bioresorbable Vascular Scaffold (BVS) System (Abbott Vascular; Abbott Park, Illinois) is now available based on the pivotal ABSORB III trial.[3] That was a noninferiority study compared against the everolimus-eluting stent (Absorb; Abbott Vascular) made by the same manufacturer.

The background of this is twofold. One is that percutaneous coronary intervention (PCI) has become sophisticated now. The stents are excellent: They have very low rates of stent thrombosis and very low rates of target lesion revascularization. But, at the end of the day, we're still leaving a metal cage inside the artery. The question is: If that [cage] goes away, is that beneficial for patients? In the ABSORB III experience,[1] it was a noninferiority trial with a signal for potential late stent thrombosis or scaffold thrombosis, as the case may be, in the BVS arm. When you parse the data, it looks like it was probably in smaller vessels less than 2.5 mm in diameter.

Dr Harrington: Let's stop at that because that is what was known before we saw the results today. As I think about the bioresorbable stent, it really takes me back many years. As you know, our mutual colleague Richard Stack was working on this back in the '80s and '90s. When I arrived at Duke, there was a program underway in Richard's lab looking at bioabsorbable stents. They never figured out the polymer issue in terms of it causing an inflammatory reaction. A lot of that research got shelved. How many times has a patient asked you, "Doc, what happens to that metal that you put in my heart? Can you take it back out if I have a problem? What if I need bypass surgery? Can you get around it?" These are legitimate concerns. I agree with you. Stents are interesting again.

Dr Rao: They are. The reality is that we're not talking a lot about physiology like we used to in the old days. But there are some issues with the vasomotor reactivity of coronaries and what that translates into in terms of clinical outcome. If you have a platform that eventually goes away, does that restore vasomotor reactivity of the vessel? Does it become normal again?

Dr Harrington: Great question.

Dr Rao: Yes, and patients are very interested in that.

Dr Harrington: Patients are really interested; and certainly after the ABSORB III results came out, it led to approval of the device for commercial use in the United States.[2] It had already been used in other areas of the world, which is not unusual.

Dr Rao: Absolutely. Other people outside the United States were using it, for example, in the very young patient, a 40-year-old who may have a long life and require bypass surgery at some point in the future.

Tradeoffs in Noninferiority Trial Design

Dr Harrington: Let me ask you, because you and I both are clinical trial nerds. When we talk about the different types of trials—superiority, noninferiority—we always want to have a reason that we did noninferiority. I am a simple guy, and I like to think of noninferiority as a great trial design when you are willing to give up something, but you have to get something in return. Usually I think of it this way: Is it safer? Is it easier to use? Or might it be cheaper? From my vantage point—and you know I don't do interventions any longer—it does not seem that any of those criteria were met.

Dr Rao: That is exactly right. I mean, you taught me how to do interventions, and you taught me how to do clinical trials. I agree with you. The noninferiority [trial] is a bit of a tough nut to crack because there is a difference between equivalence and noninferiority. Noninferiority does not mean that they are exactly the same. You are giving up something in order to gain something else.

Dr Harrington: That is that concept of the minimally important difference. You've got to decide: What am I willing to give up in order to get something? The classic example is if you are using a fibrinolytic agent, and it is associated with less stroke, less hemorrhagic stroke. What would you be willing to give up?

Dr Rao: Yes, and those are qualitative judgments. In the setting that we're talking about, you are [comparing] a scaffold against a very mature technology that many interventional cardiologists are comfortable with. We have large studies showing that they are safe. The noninferiority trial design is challenging in that setting because what are we giving up?

Dr Harrington: What are we giving up, and what are we getting in exchange?

Dr Rao: Exactly.

New at TCT: ABSORB Follow-up and Imaging Comparisons

Dr Harrington: Let us talk about what we saw today.

Dr Rao: Today, they presented the 3-year follow-up with the ABSORB II experience, which is outside the United States. The reason that this is important is that in most patients, the scaffold will have resorbed by 3 years. The question is: Is vasomotor reactivity restored? This was a trial about which I think most of us, before coming to Washington, DC, thought, "That is interesting, but that is not really what I am going to pay attention to."

Dr Harrington: Right.

Dr Rao: Honestly, I think it is fair to say that the results were a bombshell.

Dr Harrington: I think that the Twittersphere was saying "shocked the world" or "really changed the game." People were saying, "Wow, this is amazing."

Dr Rao: Yes, because it actually showed no difference in vasomotor reactivity between the metal platform and the BVS. And there is a safety signal again with increased scaffold thrombosis compared with stent thrombosis.

Dr Harrington: Fair to say, Sunil, like a lot of big trial results that sort of catch you by surprise. We've got to think about this one.

Dr Rao: Absolutely.

Dr Harrington: I do not think that any of us are ready to go in one direction or the other, but clearly work needs to be done.

Dr Rao: I agree. I think for the regulatory bodies, this is going to be a very challenging time because the bioresorbable stent is available now. The scaffold is available.

Dr Harrington: Yes, they are going to have to address how to incorporate this new piece of information into what is already out there. So, a lot is still to come. The second really interesting study [relates to] stent expansion. Antonio Colombo and others taught us a lot in the '90s, [including the fact that] you had to fully expand the stent. That, plus dual antiplatelet therapy, changed the game in acute stent thrombosis. Now, a randomized trial of three different imaging modalities investigates stent expansion. Why don't you tell people what it was about?

Dr Rao: This is a great study. In fact, it is somewhat related to the BVS because one of the issues around BVS is not only vessel preparation for optimal stent expansion, but also, imaging is recommended when you are using the BVS.

Dr Harrington: Right, to ensure that you fully expanded it.

Dr Rao: That you don't have areas of prolapse, for example. ILUMIEN III, results of which were presented today by Ziad Ali and published in The Lancet, is a very nice study.[4] It is great to see diagnostic tests.

Dr Harrington: Elegantly done.

Dr Rao: Absolutely. [Participants were] randomly assigned to angiography-alone guided stent delivery, IVUS—which is what is widely available, or OCT (much higher resolution images but not as widely available). The primary endpoint was a surrogate of stent expansion.

Dr Harrington: Not a big study: 400 to 500 patients.

Dr Rao: Exactly, relatively small. It was a fascinating study because it showed that there was no significant difference in stent expansion across the different modalities. That tells us a couple of things. One is that with a mature procedure like PCI, its operators who participated in this trial are pretty good with their eyes.

Dr Harrington: Actually, very good with their eyes.

Dr Rao: It also tells us that we need a lot more information about these technologies. And it makes us question whether more information is necessarily better information. That's an important point because with high-resolution imaging, you start seeing these little details like dissections and edge dissections. Is that clinically meaningful when, without that imaging technology, the patient would have done fine?

Dr Harrington: It reminds me of something I was taught when I was a fellow in the cath lab. Don't let perfection be the enemy of good. It might be that a certain level of imaging or certain level of resolution is good enough for clinical decision-making. But in the last part of the abstract, they make the comment that larger trials are warranted. They probably are, to get into the clinical outcomes.

Dr Rao: I think so. What is fascinating about this is that this next trial, which is probably going to be powered for clinical outcomes, is examining the effect of a diagnostic modality on clinical outcomes. I just find that fascinating.

Dr Harrington: It is because so many things make their way into clinical practice because the images are prettier, and you can see more. And the question is: Does that incremental information actually change [how] patients do? In an era when we cannot pay for everything, we've got to figure that out.

Radial Cath as a Quality Indicator?

Dr Harrington: You have certainly been one of the major proponents of [radial artery catheterization]. You have changed practice, I would say fairly, across not just your own institution but in many ways across the country. You have been out there teaching. Now, there is a buzz afoot to say radial cath, radial access, might be a quality indicator.

Dr Rao: Yes. I struggle with that a little bit. Obviously, I am a big believer in radial. I think the data are very strong. What is probably going to drive the adoption is not just the incoming generation of interventional cardiologists who are trained, but there are also going to be financial pressures. We're all anxious about the acute myocardial infarction (MI) bundling with 90-day outcomes. In that environment, any strategy that is going to increase the efficiency and the safety of a procedure, so you can get the patient out faster, is probably going to become the dominant one.

I struggle a bit with this whole issue of a quality indicator because I like to have changes occur from within the profession rather than having it come from outside the profession and have some kind of penalty against it. I hesitate a little bit. But I do think that centers that are going to be practicing radial procedures at high volume are going to have better outcomes, and they are just practicing better quality PCI. Dr Harrington: We saw the recent paper of ST elevation MI, that it does matter where you get your care.[5] Your point is well taken as we talk about bundles. Care is bundled. Because you do something one way, that may well portend that you do things well other ways.

Dr Rao: Yes, it is a marker, I think, for other care pathways and processes.

Dr Harrington: I agree with you. I think that we would like the change to come from within, but I will push back a little bit and say [that] sometimes we need external forces to push us a little bit.

Dr Rao: I agree with that. I think that is probably what is going to happen with radial access.

Dr Harrington: Great discussion. I look forward to catching up with you at AHA, and maybe we can talk more about bioresorbable stenting because I do think people are going to be looking at these data [closely] over the next few weeks.

Dr Rao: Great, thanks again, Bob.

Dr Harrington: Thanks for joining me, Sunil. And thank you for listening.


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