Cardiovascular Innovation: Dying or Thriving?

; Robert A. Byrne, MB BCh, PhD


October 27, 2016

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Robert A. Harrington, MD: Hi. I'm Bob Harrington, from Stanford University. I'm here at the European Society of Cardiology meeting in Rome, Italy, and have had the opportunity to talk with colleagues on the important topic of whether cardiovascular innovation is dying or thriving. Joining me today is Dr Rob Byrne from the German Heart Center.

Robert A. Byrne, MB, BCH, PhD: Thanks, Bob.

Dr Harrington: The German Heart Center is in Munich, Germany. We are glad that you joined us here today.

Dr Byrne: Yes, it's great to be here. [Innovation in cardiovascular medicine is] a topic that comes up a lot.

Cardiovascular Drug and Device Innovation

Dr Harrington: Let me try to frame it. We will spend 2 or 3 minutes on drugs, and the rest of the time on cardiovascular devices.

In the drug world, we have had tremendous success in reducing cardiovascular death and disability with angiotensin-converting-enzyme (ACE) inhibitors; antiplatelet therapy; anticoagulants; statin therapy; and other ways of lowering lipids, beta-blockers. That is a tremendous achievement requiring innovation and large clinical trials. Almost all of these drugs now, at least in the United States, are generic. What we see is that many generic drugs are available that work. What are we going to do to add onto that or replace it?

Dr Byrne: Certainly, we have made great progress. If you look at cardiovascular mortality between the 1960s and nowadays, we have seen a dramatic reduction—maybe a fourfold reduction. And a lot of this has come through new drugs and new devices, and they're testing in comparative efficacy studies.

Recent years have shown us that there is still room for innovation. From a drug point of view, we have the exciting advent of PCSK9 inhibitor therapy, which will serve an unmet clinical need for our patients. We have newer therapies for heart failure that have shown a further mortality reduction in heart failure[1]—something that perhaps we didn't expect.

So, for me, we have made a lot of progress. We have great generics that improve our patient outcomes, but we also have room for new innovations and new medications, and these are coming.

Dr Harrington: So even though we see a decline in new cardiovascular drugs entering clinical trials[2] (relative to, for example, cancer drugs entering clinical trials), you remain optimistic that new targets will be found—new biological mechanisms will be found that deserve or warrant testing. You are pretty bullish on the whole.

Dr Byrne: Yes. As I said, we still have unmet clinical need when it comes to longer-term outcomes, and I think we will continue to see development in the coming years.

Dr Harrington: I'm particularly excited about applying new analytical methods to existing data to find new targets and to explore new avenues of biology through the knowledge of the genome. The PCSK9 story that you alluded to is a great genetic story: the identification of [the target], testing of the concept in animals, and development of a human therapeutic. I am excited about seeing [more data on that] later this year.

Let's switch to your area, which is interventional cardiology, and talk about devices. Certainly, interventional cardiology has been one of the major proving grounds for innovation in the past couple of decades. What is going on today that excites you that you see as innovative, new technologies pushing forward?

Dr Byrne: We continue to see progress in terms of coronary intervention and in terms of structural heart disease. Of course, progress in structural heart disease has received a lot of attention, but there are also many innovations in coronary intervention. This is a rapidly developing space.

Bioresorbable stent technology is one that has received a lot of attention. We have made significant progress with new-generation devices that received CE mark approval in Europe some years ago (actually, 5 years ago), and just this year from the US Food and Drug Administration (FDA).[3]

At the same time, these new bioresorbable stents, the fully bioresorbable scaffolds, still have issues with regard to strut thickness and radial strength. Although we can judge these devices only on the basis of the data that we have at the moment, we should bear in mind that they are first-generation devices. There is a lot of hope for improvement in fully bioresorbable scaffolds.

US vs EU Approval Speed and Standards

Dr Harrington: Before we move into structural heart disease, including aortic valve and mitral valve technologies, I want to pick up on your comment that although [bioresorbable stents] have been CE mark-approved for 5 years, they were just approved this year by the FDA. Why the gap? We've talked before at these meetings about a gap existing. Why do you think there is a gap between what we do in our country and what you do in Europe?

Dr Byrne: The gap is an area that we have been involved with quite actively in the past 2 or 3 years, because the European commission has come to us physicians and asked for guidance in drawing up new guidelines for CE mark. The European system is more permissive than the FDA system, but I would argue that this has not served us poorly as Europeans. We have had early access to devices, scaffolds, and transcatheter aortic valve replacement (TAVR) technologies. This has been important to treat patients who needed this therapy. The FDA approach sets the bar higher, and there is a lower likelihood of technologies that don't work making it to market.

Dr Harrington: It's an interesting dilemma, isn't it? In some ways, the combination of the two approaches works well for what I'll call the "global" community of patients. The permissiveness—and maybe the ability to innovate more quickly—has certainly benefited both European patients and European investigators. Maybe the field has moved at least in part because of some of the requirements set by the FDA.

Dr Byrne: That is a very good comment relative to drug-coated balloons and polymer-coated stents. The companies have had to deal with issues that have arisen with regard to the bar set by the FDA approval, and this has resulted in better products.

I would reemphasize that the European model has generally served us quite well, but it must be coupled with quite rigorous postmarketing surveillance. This will then lead to devices that are withdrawn. We have to accept that as part of the regulatory model. A recent study showed higher rates of device withdrawal in Europe compared with the United States.[4] This fits with the model, and you accept it as part of the price you pay.

Dr Harrington: Yes, exactly. If you think about it from the global community perspective, the balance of the two approaches might be something that we need as a community optimally.

Let me ask you in the closing minute or two: What excites you in TAVR and in mitral valve disease?

Dr Byrne: It's remarkable to think of the progress that we have made with TAVR in the past 14 years, from the first implantation of a valve in humans to a therapy that is now offered every day to our patients, with ever-improving outcomes—and now to intermediate- and high-risk patients, not just patients with prohibitive high risk. So this is a space that is still developing.

Of course, we have many, many devices available with CE mark approval. Much progress has been made in terms of reducing paravalvular leak, in terms of reducing vascular complications through having lower sheath sizes. This is probably the area that is going to receive the most focus in the years to come.

Coupled with that, the mitral valve space has exploded. We realize that (A) this is a potential area or growth space that is very broad because so many patients have mitral valve disease and (B) it's a much more complex area to deal with than TAVR. You don't typically have heavily calcified valve leaflets to enable you to work with valve technologies in de novo valves. And you have, of course, complex interaction between the subvalvular apparatus and the valve itself. But I think the number of valves that have reached early-stage clinical testing is encouraging. And I am pretty sure that in the coming 5 years, we are going to see progress on that.

Dr Harrington: Yes, it's amazing to me that the geometry and the physiology of the mitral valve are such that the technical issues are a lot tougher to overcome than the aortic valve. But I agree with you that in many ways, it's an engineering problem and we need to figure it out.

Just 30 seconds on hypertrophic cardiomyopathy. Is alcohol ablation the best we can do?

Alcohol Ablation for Cardiomyopathy

Dr Byrne: I have to say that in our practice, [alcohol ablation is] what we do when we treat the hypertrophic cardiomyopathy patients. We have good results with this technology. We are making a lot more progress in risk-stratifying our patients, and we have adopted new risk stratification scores in Europe with regard to the prevention of sudden cardiac death. But alcohol septal ablation is where it is at for us. I don't know how things are looking Stateside.

Dr Harrington: We see two things. One is the growing recognition that places are going to have to do more volume to be good at taking care of hypertrophic cardiomyopathy patients,[5] and second, risk stratification is critical—we can't just lump all of these patients together. There are probably some characteristics that favor aggressive intervention. There is also a whole series of drugs now being developed for treatment in this space, so there is a lot more to come.

Rob, thank you for joining me here today, and thank you, our listeners, for joining us on Medscape Cardiology to talk about cardiovascular innovation. My guest today has been Dr Rob Byrne from the German Heart Center in Munich, Germany.


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