Stents + Sensibility: Talking Technology + Trends with Cardiology Device Makers

Cardiovascular Business invited the chief medical officers of three stent companies to discuss the usage of new and old technologies; why they may diversify their product lines to include healthcare services, such as cardiac catheterization laboratory management; and predictions for the future. Moderating the conversation is interventional cardiologist, health outcomes researcher and CVB editorial advisory board member David J. Cohen, MD, MSc. Roundtable participants are:

• Keith Dawkins, MD, chief medical officer and executive vice president of Boston Scientific
• Martin T. Rothman, MD, chief medical officer and vice president of medical affairs for the structural heart, coronary and renal denervation division at Medtronic
• Chuck Simonton, MD, chief medical officer and vice president of vascular global medical affairs
  at Abbott

Balancing Enthusiasm & Skepticism as Innovations Emerge

When the one-year results of the multicenter, randomized clinical trial ABSORB III were presented in late 2015, the investigators noted that it would take up to five years to determine whether the bioresorbable vascular scaffold (BVS) technology is superior to metallic stents (N Engl J Med 2015;373[20]:1905-15). In July, the FDA approved the Absorb GT1 Bioresorbable Vascular Scaffold System (Abbott) and issued instructions that include cautions about patient and lesion selection as well as implantation technique.

Two months later, Ronald Waksman, MD, of Medstar Washington Hospital Center, noted that BVS usage was under 5 percent globally for reasons including “fear of scaffold thrombosis, lack of short-term benefit, incomplete matrix of sizes and lengths, and a suboptimal profile of the device when compared to [drug-eluting stents]” (Cardiovasc Revasc Med 2016;17[6]:353-4). 

As BVS and other new tools enter the interventional cardiology armamentarium, they may arrive with questions about how enthusiastically practitioners should embrace new innovations whose value has not yet been proven.

CVB: Let’s talk about the benefits and trade-offs interventional cardiologists face when deciding whether to use new stent products. The best current example is BVS, where the true value is unproven beyond the first-generation technology we have and it’s likely going to remain that way for a few years. On one hand, patients and clinicians are excited about new innovation; on the other, BVS cost more and are a little harder to use. How should practicing cardiologists think about new products before their value is proven?

Simonton: In the plumbing years, we were using everything we could just to get a blockage open and relieve ischemia, particularly in patients with acute coronary syndrome. Doctors weren’t paying much attention to what happens to patients after the first year. We now have interventional cardiologists having to do extreme things to treat a growing snowball of patients with permanent metallic stents coming back two to five years after angioplasty with restenosis and layers of stents requiring old-fashioned treatments that we now know work only temporarily, such as brachytherapy, which is increasing in frequency.

The reason I would be looking at a bioresorbable scaffold as my default in almost every patient with an active lifestyle and at least a three- to five-year life expectancy is to get rid of metal hanging around in people’s hearts for the rest of their lives and serving absolutely no function because, as individual cardiologists, we’re not curing coronary artery disease. Twenty years ago, if we’d been able to leave nothing behind, as physicians treating blockages in the periphery try to do, we wouldn’t be putting metallic stents in today.

Not all cases are going to be suitable for Absorb, of course. It’s thicker-strutted and takes a little longer to deliver. You just have to be diligent about predilation, sizing and postdilation. The average difference between implanting a metallic stent and Absorb was about 4 minutes in the randomized trials. In complex cases, maybe it’s 5 to 10 minutes, but we’re talking about 10 minutes extra for perhaps 10 years of life without a metallic stent in a patient’s heart.

CVB: I appreciate the BVS concept, but right now it’s unproven. All the things you talked about are theoretically nice and may turn out to be true. How do we choose when we have unproven benefits? We’ve all seen good theories come and go. Should we wait 10 years for the data, or should we push forward because we’re innovators?

Dawkins: The cadence of device development has slowed and the investment in drug-eluting stents (DES) is now more diversified to other cardiovascular products, particularly structural heart therapies. That reflects, in part, the fact that it is difficult to demonstrate that any new device is better than the devices we already have.

Most of the time, we’ve initially focused on acute performance. In the U.S., the average interventional cardiologist undertakes fewer than 50 PCIs a year and, in California, less than 30. Therefore, every cardiologist worldwide, but also, of course, in the U.S., wants a device he or she can deliver. If the cardiologist can’t deliver the device, then we don’t need to talk about polymer, drug, early reabsorption or anything else, because if you can’t deliver the device, the lesion is still a problem.

The first generation of fully resorbable stents obviously has some challenges in terms of key performance. … What none of us knows is, if we were having this conversation in five years’ time, is the penetration of these products 10 percent, 40 percent or 80 percent? If it’s 80 percent, all of us should be in it. If it’s 40 percent, we should probably all be in it. But if it’s 10 percent, then it’s a niche product.

The question is whether our investment is better directed to something else like structural heart. No one can answer that question, but it is really important to all of us involved in strategic decisions around investment.

CVB: Obviously, Medtronic has investments in different approaches to this issue, but as a clinician, is the promise enough to make you want to use something that’s a little harder to use and maybe has a little bit of an early safety challenge? Is that a fair trade-off?

Rothman: I’ll answer the question in the spirit in which I think you’re asking it, which is to consider this from a clinical, rather than a corporate, perspective. My sense is that when you take a new technology which is very different, then you have to make a really hard, clinically based, research-based judgment. When BVS came out, it seemed to me that it should be properly scientifically evaluated. Until such time, it should not be considered to be a standard therapy. In other words, it shouldn’t be for all-comers to use just because they feel they like something new. We are tempted as physicians to use new technology because it sounds great and we love to be using new stuff, but really we’ve got to temper that with science and say, “I’m not prepared to put my 45-year-old LAD patient who is a breadwinner into what is effectively a research study, even though he doesn’t know it.” My view is no, you’re not allowed to do that. To me, the jury’s out. The data’s not long term enough for this.

In my view as a clinician and a Medtronic internal advisor on research and expenditure, I like to spend our money on areas where there is a clear demand for technology, which often means unmet needs. If I can make a comparison, we have excellent architectural framed stents that do great work. Getting a “better-than” result is going to be nigh on impossible. We already have a very good solution with a very good clinical outcome. I doubt that any device in the future will actually be “better than” what we’ve got. I’d rather spend my money on new technologies like aortic valve treatments, which were unmet needs when we acquired CoreValve.

CVB: Obviously, different companies have chosen to look at the question differently, but it struck me as interesting because it’s now in front of me as a practitioner. Patients come in. Most of them are not specifically asking for a particular technology. We have to decide if the promise will ever be realized. Is it worth the challenges now?

Obviously, the market will tell us some things but I think that it is, at some level, a research study because the five- to 10-year answers are what drive the decision, but we don’t know the answer yet.

Rothman: You mentioned patients coming to us. That’s something we encourage, to have honest discussions about technology with patients, but to be fair and honest about things like informed consent, patients don’t understand the level of detail that is contained in all of the ABSORB data and, by comparison, in all of the other DES data sets. The fact that a patient asks for something doesn’t mean the physician should give it. The physician is there to gate-keep the patient.

Simonton: I’ve got to object to anybody saying that offering a patient Absorb in the U.S. today is an experiment. This device has been through an extremely rigorous randomized trial in the U.S. It had an overwhelmingly positive FDA panel endorsement. Because of what we can do in device medicine—as opposed to drug therapy—we fine-tune how we use a device based on what the data show.

I believe the reason the FDA panel was so overwhelmingly positive was because it’s clear this technology should be available to patients. When you place Absorb in the right patients in the right vessels with the right technique, which is a fairly simple, straight-forward angioplasty technique, in vessels that are sizable and right for the device, the safety outcomes are spot-on with the safest DES in the world.

Dawkins: There are a lot of caveats in the restrictions placed on the use of the product. I think the FDA panel was overwhelmingly positive because it knew this was the beginning of a new class of technology, which they did not want to be responsible for withholding from U.S. patients, but from the pivotal trial, the acute performance was statistically inferior to the Xience stent.

We will see when it’s been in the U.S. for 12 months. That will be very interesting. This is an important technology that can be replaced by something thinner, more easy to deliver and more easy to dilate.

CVB: Like the answer to many things, time will tell the ultimate answer on where this field and this technology go.

Impact of Economics, Education & Unmet Need

CVB: Given the interest these days in cost-effectiveness, quality of life, readmissions, all of the longitudinal aspects of care, how do your companies think about these aspects when you’re deciding which new products to develop or indications to pursue? How do these longer-term outcomes come into focus?

Rothman: I’m tempted to think away from stents because a lot of the stent-related issues have been resolved. Whilst each of us has to look at maintaining market share because, obviously, stents are a meaningful part of our business, it’s also clearly a diminishing return as we see a decrement on an annual basis of 8 to 10 percent in end-user prices for stents. You have to look at refreshing your product lines but also finding new business opportunities. That sounds very commercial, but from my point of view, it’s about finding new treatments to help diseases that aren’t met well today. But that brings up another conundrum, which is that the cost of innovation is going up. The time to delivery of that innovation to the marketplace is getting longer. The income that we generate is getting smaller. There’s a paradox going on.

Also, it’s much more difficult for companies to provide education opportunities now because of the limitations in what you can provide to physicians and healthcare workers but, nonetheless, it’s still an important part of our business to educate people so they know when to use products. All of that matches together, but from our point of view, it’s about developing the new strategy and then backing that with good science.

It’s the product, the opportunity and making the market, which also is sometimes about changing healthcare, patient flows and educating people into new opportunities, which is also very expensive to do as you change the pattern and flow of patients. If we go back to renal denervation, the patients aren’t regularly available to the people who would quite like to do the procedure: the interventional cardiologist and the interventional electrophysiologist. If you’re going to think about making a market in that difficult area, you have to think about the primary care physician and the person who cares for the hypertensive patient and allow them to understand the gains that might be had by a therapy which has unproven potential. There are all these different factors which you have to think about as investment into a new opportunity.

Simonton: I think it’s a combination of innovation that solves unmet clinical needs but also expanding it to have the breadth of products as a company that you can meet the economic demands out there.

Abbott’s strategy is focused on innovation and leading the field. In April 2016, we announced plans to acquire St. Jude Medical. That combination of product portfolios will allow us to expand into heart failure, an extremely large area of unmet clinical needs. From a strategic standpoint in the cardiovascular space, the things that we look at now are valvular disease, heart failure—but preserved ejection fraction heart failure (what we used to call diastolic heart failure) as well as systolic heart failure—and arrhythmias.

Bringing St. Jude Medical into the mix will mean innovation in several disease categories with breadth of products to help with the economic demand and enable broader contracting with hospital systems. Companies have to be able to bring products to the marketplace and understand the economic stresses on the hospital systems.

Dawkins: The health economics is key. The disconnect between reimbursement and regulatory approval, which may just be a form of rationing, is very real. In Europe and France, you look for CE mark but if you can’t show a health economic benefit, you don’t get reimbursement. The regulatory pathway is in many ways taking second fiddle to the reimbursement pathway.

We would not design a trial today that didn’t have health economics experts intimately involved from the beginning. For example, Synergy and short-term antiplatelet therapy. If you look at the holistic costs of the whole procedure to the payer, whoever it happens to be, it’s the drugs plus the stent. We want to integrate the total  cost when we analyze our data.

The Watchman device, for left atrial appendage closure, is another interesting health economic challenge because you’re comparing the device with warfarin or NOACs [novel oral anticoagulants], which have a constant 3 percent per year major bleeding hazard, as opposed to a device that has a small periprocedural risk and then a flat risk moving forward. At some point, the adverse event lines cross. We are investigating those sort of health economics to show the benefit of the device in the long term due to the risk of stroke, which from a healthcare cost point of view is a catastrophe.

Risk Sharing: Eventually, Inevitably  

CVB: Let’s go outside of devices per se and away from product development to the role vendors may play in supporting cardiovascular service lines. Pharmaceutical companies are starting to do risk sharing for very expensive drugs, and device companies are offering services to help manage cardiac catheterization laboratories and heart failure programs. Where do you stand with these concepts? 

Rothman: You have to have a long-term strategy in your head about who you are going to be over the next 10,  20 or 30 years, and being a device maker is not everything. We’ve taken a view that Medtronic needs to be involved in healthcare strategy. We want to open opportunities for healthcare provision where it doesn’t exist and that looks at emerging areas that, for example, don’t have acute myocardial infarction cover and help start up programs. But those areas eventually end up being device-oriented processes; they end up selling more product.

Where it gets more interesting is in the value-based healthcare discussion, which is about trying to share risk between the provider, the health insurer and the device manufacturer. It almost always challenges the device manufacturer to put his money where his mouth is. If our product is so good and does reduce outcome events, then maybe we should share risk.

It’s an interesting philosophical conversation. It’s much tougher to tie down into practice. There are so many factors which affect outcome, which are over and above the acute procedure, the quality of the surgeon, the quality of after-care, whether the patient is compliant with drugs. Whilst Medtronic will actively participate in developing it, I think it’s still somewhat experimental to talk about value-based healthcare. My sense is that it’s a future challenge for all of us.

We’ve already got a risk-share program we’ve established as a starter in this area, but I think there’s a lot to learn. A lot to be gained but a lot to learn.

CVB: It’s coming to the U.S. We are going to have bundled payments under Medicare, so it’s happening. Do device companies belong in this space?

Simonton: It’s very early. You have to decide as a company what you want to be. You can’t be all things to all people on all fronts. You don’t want to dilute your innovation

and what you’re doing to bring new devices forward by instead focusing on trying to help hospitals do better at what they’re already focused on, which is running their cath labs and doing them efficiently and being successful in their healthcare delivery. But you can partner to some degree in that, when you bring a new product to a hospital or when you partner with them on a product, you come with data that show there’s advantages to it. And you can partner in a risk-sharing model where you try to reduce the 30-day readmission rate these hospitals have.

Going forward, this is going to extend to longer and longer time periods. The big hospitals in the U.S. are trying to prepare for what will eventually become capitated care, where the hospital will be responsible for the patient for as long as that patient is in their hospital system. It will move to six months, to one year and then, probably, at some point even beyond. The hospitals are focused on quality, concerned about outcomes, in addition to just volumes.

Once the fee-per-service model starts to move more toward these capitated systems, companies are going to want to partner. But it’s early. We’ve got a lot of interesting programs that we’re working on right now and we’ll see what happens in the future.

Dawkins: Most people think that future investment dollars will go into prediction, prevention and monitoring as opposed to treatment. We all have to be aware of that. At Boston Scientific, we have a healthcare solution set with four strands: performance optimization, care partner transformation, patient management and capital financing.

Capital financing is easy. It’s very easy and a strategic fit to finance your next cath lab, but some of the other things, like performance optimization and care partner transformation, are what we do every day on a production line to get the best out of our manufacturing processes. The use of cath labs, in terms of efficiency, is pretty poor, lots of delays between cases, not used 24/7, not starting or finishing on time; we can help to optimize that.

If down the line, they need a Boston Scientific device, fine, but providing a healthcare solution to a hospital system is really important. We’re putting more effort into this, it’s much more difficult than just making the next stent, more fuzzy around the edges.

Goodbye to Bare-metal Stents?

Investigators for NORSTENT (Norwegian Coronary Stent Trial) found no significant difference in the primary endpoint of death or nonfatal spontaneous myocardial infarction between bare-metal stents (BMS) and second-generation drug-eluting stents (DES) at six years in patients with stable or unstable coronary artery disease (N Engl J Med online August 29, 2016).

The largest randomized DES vs. BMS trial in history, NORSTENT’s secondary finding was that the DES patients were less likely than BMS patients to need repeat revascularization or to experience stent thrombosis. For many, the results confirmed that DES are superior to BMS; however, in an editorial accompanying the trial results, Eric R. Bates, MD, of the University of Michigan Medical Center, wrote that BMS remain “an important option for PCI in some patients.”

CVB: Is there a role for BMS now? All of the companies represented here still make them, but do we need them?

Dawkins: BMS are used in about 5 percent of patients around the world. We’re undertaking the SENIOR trial in Europe, looking at an elderly group of patients randomized to Synergy or a BMS, who sometimes have confusion related to antiplatelet therapy.

I think BMS is going to be a niche product. As far as Boston Scientific is concerned, it’s not an area that we are going to invest a lot of money moving forward. A few patients—those with large right coronary arteries, very big vessels, patients who can’t take DAPT [dual antiplatelet therapy]—may be eligible for BMS but I don’t think it’s something from a commercial point of view that is of major interest.

CVB: The idea that it’s a niche product is probably pretty fair, but is there any role at all? If you were stocking a cath lab today, would you have BMS on the shelf? Do we need them?

Rothman: At Medtronic, we’ve taken a different view in that what we try to do is pick up on the BMS simplicity with what we call a drug-filled stent. That’s a stent that has no polymer on it, which some of us believe actually can lead to some of the complications of DES. Our move in a direction of BMS is to have a stent which has abluminal holes that allow the osmosis of rapamycin from within the stents to the tissue. This new technology takes advantage of some of the outcomes that we’ve seen that are beneficial for BMS. Now if that promise holds, then we might be able to address patients who can’t tolerate DAPT, or not for long, or are inconsistent in compliance.

I’m not sure that BMS on its own will grow back above about 5 percent.

Simonton: BMS are for patients that you really think can’t even take more than a month of DAPT, for whatever reason, or it’s a complex case. You don’t want to leave them with a situation where they’re going to have to come off DAPT and be at risk, but those patients are extremely uncommon now. We can almost always get patients at least to a month and oftentimes to three months on DAPT with DES and not have to worry about thrombosis.

There’s no advantage to a bare metal surface. I don’t know why anybody would want a BMS. The guidelines have moved to the point where, if a patient is at high bleeding risk, three months looks like it’s safe enough. BMS will become very niched and probably disappear in the next several years.

CVB: It would certainly make life simpler on the stocking side of things. It still comes up with atrial fibrillation. That’s the biggest place where you’re just never quite sure as a clinician these days. In an 80-year-old patient with AFib, you do not want to stop some form of an oral anticoagulant. What’s the safest, best way to get him or her to the point where the vessel is healed?

Dawkins: With that patient, we’ve emphasized the polymer and drug going away very quickly. You’re concerned about your elderly patient on triple therapy. We’re doing a post-approval study in the U.S. of patients treated with three months of DAPT. We’ve also got a trial in Europe with one month of DAPT. The question is whether they could come off DAPT very early or whether they could reduce DAPT to a single antiplatelet agent.

CVB: Right. Those studies, and others like LEADERS-FREE (N Engl J Med 2015;373[21]:2038-47) with a completely polymer-free DES, are very interesting and important because AFib is an epidemic that isn’t going away anytime soon.

Transformation in Ten?

CVB: If you look ahead 10 years, what emerging technology or trend is most intriguing to you, and why?

Dawkins: It’s going to be transformational. We’re surrounded by transformational stuff in our everyday life: uberization, Airbnb, social media and so on. If we carry on doing what we’re doing, in 10 years, we’ll have a bit of a problem. Personally, I believe the smartphone will be the center of the medical universe, both for monitoring care and actually providing care and then closing the loop between the results and changing care.

At the moment, of course, the smartphone is for the “worried well” who have a Fitbit. It’s not the people who are really sick, but there will never be enough doctors, nurses or nurse practitioners. Therefore, we have to empower patients to look after their healthcare through their smartphone. That is a really big challenge for all of us. In 10 years, that’s what we’ll be doing.

Rothman: I wouldn’t disagree. Intelligent communications and analytic algorithms to keep patients out of hospital have got to be one of the major drivers because we can’t afford the healthcare that we’re currently providing, let alone what it will turn into in the future. Unless we pull the see-saw down on the cost side, we can’t actually keep going on the device side. For example, LVADs are grossly underused and have complications, but the healthcare economy can’t really afford them. How do we invest in those sorts of important areas if there are no other solutions?

We have to conserve money on the expenditure side. Information technology will be an answer to all of that, but in a microcosm and a slightly shorter horizon, the world of structural heart disease has seen massive change, and will continue to grow if mitral valve disease can be managed in an interesting and simple way. Likewise, heart failure is probably the most expensive cardiovascular problem in the world and in the U.S., particularly. Again, IT technology is key for keeping patients out of hospital with not just weight management or edema management but to actually change therapies, control patients and make it easy to do.

Simonton: It’s going to be connectivity, information management and big data to map out the right patients for the right procedures. In addition, personalized medicine will become a reality in the next decade. We’ll start to understand more and more about the polymorphisms associated with certain diseases that put patients at higher risk. Patients will be better armed with information—the democratization of medicine. A lot of that will be from genetics, proteinomics and metabolomics. That’s going to be big. 

Where I see cardiovascular care going is primarily in trying to keep patients from getting to the point where they need an LVAD and a heart transplant, working upstream with device therapies that can reduce the burden of heart failure, which is really the end stage of many of the diseases we treat: coronary disease, structural heart disease and arrhythmias. That’s going to be a big focus in the next decade.