Affairs of the Heart
The cardiovascular sector gets to the heart of matters by continuing to roll out new products even as it deals with safety issues and slowing sales in some segments.
Jennifer Whitney, Editor
In early April, a most sensational story emerged about a man who received the transplanted heart of a suicide victim 12 years ago and recently killed himself in the same manner as the donor. The media hoopla around this story was aided by the fact that before this tragedy occurred, the man had fallen in love with the donor’s widow and married her in recent years.
The faces and names change, but scientists have reported more than 70 documented cases of transplant patients who have taken on some of the personality characteristics of their organ donor, according to a recent article in the United Kingdom’s Daily Mail newspaper. Paul Pearsall, PhD, a psychologist and author of The Heart’s Code, studied heart transplants and explored the mysterious ways a new heart could affect its recipient, such as one man’s sudden yearning for spicy foods and to study Spanish before he knew that his donor had been Hispanic. “The heart has a coded subtle knowledge connecting us to everything and everyone around us. That aggregate knowledge is our spirit and soul. . . .The heart is a sentient, thinking, feeling, communicating organ,” Pearsall has claimed.
Scientists often debunk this ideology and insist there is little compelling evidence to support it. But that doesn’t stop many people from wondering whether the heart truly is just a physical organ keeping us alive or if it also contains some fabric of our emotional tapestry. Maybe that’s added incentive to pay more attention to preventing heart disease or, if it’s too late, to seek out any lifesaving solution that will preserve the heart’s ability to thrive.
While there aren’t any proven cures for repairing a heart broken by the death of a loved one, a failed marriage or some other devastating experience, science and technology have made amazing strides in both protecting and repairing the body’s cardiovascular (CV) system. That’s good news, given that CV disease remains the leading cause of death in the United States, with more than 700,000 people dying from it annually. The economic costs related to CV disease (and stroke, a potential consequence of CV disease) are staggering, reaching $403 billion in 2006, according to the American Heart Association and National Heart, Lung and Blood Institute.
Given the enormous profit potential in serving the millions of people needing treatment and, more important, the ability to save lives, it’s no surprise that the CV market remains the largest segment in the medical device industry. Worth $21.76 billion in 2006 and projected to exceed $25 billion this year, it only will continue to grow, according to data from Kalorama Information (with offices in Rockville, MD and New York, NY), a publisher of life science research reports.
“The key trend has been that it has shifted the treatment of heart disease from the purely medical to predominantly the device field,” said Kenneth Krul, PhD, an independent consultant and information analyst for Kalorama. “Frankly, devices are more effective, although they still can use a good deal of improvement. Things like blood pressure and hyperlipidemia will always be medical issues, but overt heart disease—atherosclerosis, arrhythmias and congestive heart failure—have become predominantly device fields with medicinal support.”
Physicians clearly agree with this assessment, as was evidenced by the Heart Rhythm’s Society’s chosen theme for its annual meeting this month (May 14-17). President Bruce Lindsay, MD, told Medical Product Outsourcing that the “Gateway to the Future” theme acknowledged the rapid growth of innovative technologies in the CV field, and the society accordingly made a concerted effort to feature several sessions highlighting some of these cutting-edge technologies—including those that aren’t clinically useful yet but, on the horizon, may change the way healthcare providers approach CV disease.
Following is MPO’s examination of some of the largest CV market segments and the challenges many have faced in recent years, along with a look at what’s coming down the product pipeline.
Stents: Controversy Giving Way to Advances
These days, it’s hard not to notice the media’s increasing coverage about stents, the tiny wire-mesh tubular devices used to prop open arteries after they have been cleared of plaque. Millions of patients have undergone the fairly simple implantation procedure, which involves snaking a catheter through a small incision in the groin and pushing the stent through it to reach the problematic area. There are two types of stents: the bare-metal variety, first introduced in the 1990s, and newer generations of stents (known as drug-eluting stents, or DES) coated with a drug to help prevent vessels from re-clogging.
The US stent market is worth $2.8 billion, and the combined total for the world’s seven largest markets (including the United States, several European countries and Japan) is $4.9 billion, according to Kalorama’s 2008 report, Coronary Stents: Markets and Technologies, which showed that the combined average annual growth rate for all these markets will be 6%.
The growth rate and market value used to be significantly higher. Product recalls, concerns about whether DES promote deadly blood clots and research showing that aggressive drug therapy may work just as well as stents in preventing re-stenosis (narrowing of the arteries) all have curbed use of stents in the past couple of years, bringing the market down from a previous high of about $6 billion.
If all goes well at the FDA, the Xience drug-eluding stent most likely will be competing in the US market soon. Photo courtesy of Abbot Laboratories.
That may be true—only time will tell—but new data are putting many worries about safety and efficacy to rest, and an FDA advisory panel convened in December 2006 found that when DES are used as approved, there is no increased risk of heart attack or death compared with bare-metal stents.
The reassurance these findings provide comes at a good time, as the market for DES soon will become more crowded. In the United States, only Johnson & Johnson, Boston Scientific and Medtronic currently have products approved to date, but Abbott Laboratories also has its Xience stent under review by the FDA and could gain approval sometime this quarter. Outside the United States, a larger number of DES are available.
Looking ahead, the “holy grail of innovation” most likely will be biodegradable stents, according to industry experts. Several companies are working on stents that would totally disappear after they have done their work. Abbott currently is the only company with one of these stents in a clinical trial phase. According to data from a trial report published in The Lancet in March, Abbott’s fully bioabsorbable DES had excellent clinical safety results in patients with coronary artery disease.
The advances in technology that these products represent bode well for settling some of the debates that remain with stent placement, Krul believes. “These advances may overcome a great deal of the recent scare and will certainly be driven by the scare,” he said. However, he cautioned that longer longitudinal studies and post-release studies with different clinical endpoints will be required to maintain confidence in this approach.
The FDA agrees. In March, the agency proposed tougher guidelines for DES. If they go into effect, the guidelines won’t affect stents already on the market, but the FDA did state that companies should continue to monitor—preferably for five years after implantation—the stented area for blood clots, heart attack or other complications. Any companies seeking approval for a new product would need to submit trial data on patients’ health one and two years after implantation before the stent could be approved.
CRM Market: Jolted by Recalls but Still Viable
Worth $8 billion in the seven major world markets, the cardiac rhythm management market (CRM) is the giant in the CV sector, according to Kalorama. This segment consists of devices such as pacemakers, which help regulate heartbeats, and implantable cardioverter defibrillators (ICDs), which help prevent sudden death by following the heart’s beating pattern and delivering an electric shock to reset the pattern if it becomes abnormal. Both types of devices generally have been a strong market segment over the past decade as they benefited from advanced electronics, more reliable and longer-lasting batteries and smaller sizes.
The CRM market has not been without its share of problems, though. Since 2005, a slew of product recalls have been reported by the major players in this segment. That year, Medtronic recalled approximately 87,000 ICDs when a potential for battery failure was identified; Guidant Corp. (now owned by Boston Scientific) recalled about 50,000 ICDs that had problems with circuitry and additionally reported that a faulty switch problem could impact the functionality of 45,000 other ICDs; and St. Jude Medical, which recalled about 28,000 pacemakers that may have had a leaky seal, also reported a software problem that could impact as many as 39,000 of its ICDs. Most recently (in October 2007), Medtronic suspended sales of its Sprint Fidelis lead (a wire that connects an ICD to a patient’s heart) as a result of safety issues, and late last year concerns were raised about a safety issue with one of St. Jude’s devices.
As seen with the fallout from stent concerns, the issues facing the CRM market impacted sales in recent years. According to a report presented by Wachovia Corp. during the annual meeting of the American College of Cardiology earlier this spring, ICD implantations are projected to actually decrease 2% this year in the United States. This follows a general cooling trend: ICD sales in the United States dropped from $4 billion in 2006 to $3.9 billion in 2007. Although it’s not a huge decline, it signals a transition from the approximate 28% annual growth this market saw from 2001-2005.
The Heart Rhythm Society, which serves as a provider of education and advocacy for cardiac arrhythmia professionals and patients, currently is working on a number of initiatives, such as guidelines pertaining to credentialing and physician training, geared toward patient safety in the CRM marketplace. Lindsay, who serves on a test writing committee for the American Board of Medicine, said the goal is to ensure that guidelines remain current as technologies evolve.
And evolve they will. To counter slowing sales, some manufacturers are looking to broaden the patient populations eligible for an ICD. Others are focusing on creating innovative new approaches to the traditional ICD. Inner Pulse, for example, is an emerging company based in Research Triangle Park, NC that is developing a novel ICD. Inner Pulse’s PICD device differs from what’s currently available for several reasons. Whereas a traditional ICD is a titanium stopwatch-sized box implanted in the chest during a procedure that usually requires an overnight hospital stay, the PICD would be implanted percutaneously, ideally in an outpatient setting, in a procedure that would take only about 15 minutes to complete.
“The device has been miniaturized to the point where we can take all the components and put them into something the diameter of a pencil,” explained Daniel Pelak, president and CEO of Inner Pulse. “The value driver is the ability to place it into the body with a needle stick.”
This type of minimally invasive solution would be both easy to use and well suited for primary prevention of sudden cardiac death, according to the company. “Anywhere from 15%-30% of patients who should have a defibrillator actually receive it—that means 70% of patients who should receive one don’t. The number of people who die from cardiovascular death is needlessly high,” Pelak said.
The Edwards SAPIEN valve currently is being used in a pivotal clinical trial for FDA approval involving 1,040 patients in total. The valve is implanted for aortic replacement by a minimally invasive method using a catheter, avoiding the need for a patient to undergo open-heart surgery. In April, the company also announced that the first US patients received its transcatheter heart valve implant to address a congenital heart condition in which the valve between the right ventricle and the pulmonary artery is nonfunctional. This FDA-approved feasibility trial will enroll 30 patients for pulmonary valve replacement. Photo courtesy of Edwards Lifesciences.
If the company’s supporters are any indication, many in the industry view Inner Pulse’s platform as an exciting new development in this market segment. Greatbatch, AMI Semiconductor and Enpath Medical all have provided development support, and, along with venture capitalists, financial support has come from market leaders such as Medtronic, Boston Scientific and Johnson & Johnson.
Valve Market: Steady but Significant
It may not achieve billions of dollars in sales, but the heart valve market can boast innovation, compliments of upgrades in materials and methodologies associated with these products, that has heaped plenty of positive attention on this segment. Research firm Frost & Sullivan’s report, US Artificial Heart Valve Markets, showed that revenues in this market totaled $519 million in 2005 and may reach as high as $867 million in 2012.
“We have seen a rapid progression in cardiovascular technology during the last 50 years,” said Stan Rowe, corporate vice president, Advanced Technology, for Edwards Lifesciences, based in Irvine, CA. “In this time, we’ve gone from the development of the first artificial heart valves—mechanical valves—to porcine tissue valve, then to bovine tissue valves and now transcatheter valves that can be implanted without open-heart surgery.” These developments, he added, are serving larger patient populations today and enabling them to live longer—and healthier—lives.
Improved manufacturing techniques and materials have led to more durable tissue-based valves, which now can last 20 years longer than previous generations, according to Frost & Sullivan. Along with these advances, innovations in heart valve repair products will strengthen the market in years to come.
“Recent advances in catheter technology have renewed focus on repair over replacement,” Frost & Sullivan Research Analyst Venkat Rajan noted in a 2007 press release. “Therefore, given the added physiological limitations of certain replacement valves, the majority of start-up activity has been focused on the development of tissue valve repair products.”
The growth of valve-repair products is a no-brainer: Patients prefer them, according to a report by research publisher Informa Healthcare, because the long-term outcomes are better and surgical complications are fewer than they are with replacement valves, particularly as minimally invasive techniques improve.
But repair isn’t always an option. Therefore, many companies are focusing on improving replacement products—especially given that aging populations ostensibly will increase the need for these devices in the years ahead. For its own part, Edwards Lifesciences, the market leader in the heart valve segment, is excited about the prospects for its novel approach to transcatheter valves. Developed throughout the 1990s, the first percutaneous aortic heart valve replacement was completed in a human in 2002. Since then, after a number of studies involving hundreds of patients, Edwards initiated a pivotal trial in 2007 in the United States for FDA approval of the Edwards SAPIEN valve and already has gained commercial approval in Europe.
“We believe the transcatheter heart valves and minimally invasive cardiac surgery tools and techniques will be a significant contributor for many years to come,” Rowe concluded.
LVADs/TAHs: Small Markets With Large Growth Rate Potential
Another area relying on replacement technology to keep the heart and its related systems operating smoothly is the market for left-ventricular assist devices (LVADs) and total artificial heart (TAH) products. According to Kalorama, these two device segments are valued at a total of $195 million in the United States and $395 million in the seven major world markets. Noteworthy is that while larger markets such as stents and CRM have cooled, the LVAD and TAH segments are poised to grow at a collective average annual rate of 25%. Smaller unit sizes, longer battery life and better long-term use outcomes are expected to fuel this progression.
“The LVADs are always hot because they allow patients to live somewhat normal lives without heart transplants. The enabling technologies for improved, smaller systems are coming into being, and this maintains continued interest and development,” Krul said. “TAHs will always be a hot topic but a less practical approach—and a more expensive one.”
Only one TAH is approved for use in the United States: Abiomed’s Abiocor, a self-contained system that was modified from a previous-generation Jarvik-7 design. The only approved indication here is for use in patients awaiting an organ transplant (ie, “bridge-to-transplant”), but Europe’s approvals are more flexible, allowing the product to be used over the long term (Abiomed has submitted applications to the FDA for this additional indication in the United States).
The LVAD market, meanwhile, has about 10 players with technology on the market or in development. Thoratec is the leader in this space, according to Krul, and competitors include companies such as Berlin Heart, Ventracor, Terumo and MiTi.
Although estimates show a very healthy growth progression for these market segments, Krul said the high cost for some of these segments’ products remains a hurdle.
Other Products: Complementary and Innovative
As all of the types of products in the prior product categories continue to lessen the burden on populations at risk for complications—or worse, death—from CV disease, some other advancements in technology will aid the growth of these markets.
Advances in imaging technology, for example, continue to facilitate the growth of minimally invasive surgeries. As devices get smaller, the need for high-resolution imaging only will grow greater. Therefore, a slew of new imaging modalities are in the CV pipeline.
One example of emerging technology in this realm is a new spin on an old technique called optical coherence technology (OCT), a high-resolution imaging system that has been used in ophthalmology for more than a decade. Historically, it’s been difficult to get a good look into the interior of a coronary artery, but two US companies—LightLab and CardioSpectra of Austin TX—are developing a new, improved scanning method with OCT by using the Fourier domain (a mathematical formula used to process a complex signal to differentiate its component parts and analyze them). Traditional OCT can be problematic because it can’t see through blood, and users have had to use a balloon to block incoming blood (a process that could potentially damage tissue) and flush an area being scanned with saline. The new scanning method, which initially would be used to image stents after placement to check stability and keep track of new scar tissue, would take a fraction of the time traditionally needed for OCT and reduce risk of damage to the heart, experts have reported.
With the minimally invasive surgical market broadening, there’s also no ignoring the news generated by companies working on robotics and other remote navigation systems. As the size of components shrinks and technology becomes ever-more complex, these systems are expected to play a much larger role in surgeries—experts say it’s not a question of “if,” but “when.”
Among the variety of surgical robots currently in development is a snakelike device by Carnegie Mellon University, which has partnered with startup Cardiorobotics (formerly known as Innovention Technologies). The CardioArm, operated using a computer and joystick, is a curved robot that potentially can offer surgeons both flexibility and rigidity along with precision while performing complex procedures through one small incision. The device, which can be as small as 300 mm long with a diameter of 12 mm, eventually could be made small enough to enter the bloodstream through a vessel, researchers at the university have reported. The probe has been used successfully in CV procedures on nine pigs and two human cadavers and is set for live human trials later this year, according to a recent article in Technology Review.
Along with the advances coming down the pipeline for healthcare providers, patients increasingly will become more active in their own care. As such, many will rely on home-monitoring technologies to keep track of their health. Advances in these products increasingly are offering patients the ability to transmit real-time data to healthcare providers—giving doctors the ability to make better recommendations on the timing and dosing of medications, as well as ideal times of day for CV exercise, for example. In addition to promoting patient compliance, these systems will help provide continuous—rather than episodic—data from blood pressure and other measurements, making it easier for doctors to spot problems earlier.
Cambridge Consultants, for example, is one of many companies working with this type of technology. Its “Vena” platform uses wireless technology that enables devices to deliver medical data to a central monitor (located in a patient’s home or online health record, for example). The Vena software solution could be added to a device such as a blood pressure monitor with a potential application cost of less than $10 and may be available by the end of this year, according to reports from the company.
The Overall Market: A Promising Future
Looking ahead, expect even more minimally invasive solutions in terms of both products and the procedures utilizing them.
“The value of the technology is evident in reducing disabilities, shortening procedure times and hospital stays, eliminating costly complications, easing pain and suffering and improving a patient’s quality of life,” Rowe of Edwards Lifesciences explained. “As an industry, we will be dedicated to doing what’s best for patients and helping them live healthier, happier, longer lives.”
As with many market segments within the medical device industry, demographics—that is, the aging population, our affinity with artery-clogging junk food and propensity for obesity, among many other risk factors—bode well for the need to continually release new approaches to old problems in the CV sector.
“If you look at when heart disease starts to manifest itself, demographically we’re moving straight into the eye of the storm over the next 10 years,” Pelak noted. The good news, he said, is “if we look at unmet needs, we’ve made vast strides in treating these patients. It’s made a huge difference.”
Product Safety: Watchdogs Lurking
Given all the challenges the cardiovascular (CV) market has faced during the past few years, it should come as no surprise that quality, safety and efficacy will be given tougher scrutiny by regulators and payers—not to mention patients—moving forward.
The spotlight on manufacturers of CV solutions has been intensified by the mass media’s coverage of the device sector. Although the public is growing more educated about the opportunities new technology will offer, the industry rightfully remains somewhat wary about how well consumers will understand some of the more complex issues being reported.
“Some of the things written in the media have been polarized and provocative, but the positive side is that it spurs people to look at additional safety measures. But the negative is that patients don’t know how to separate risks from benefits and may be dissuaded from having a device implanted,” explained Bruce Lindsay, MD, president of the Heart Rhythm Society.
“The cardiovascular sector has received a disproportionate amount of attention. Unfortunately, we have a situation where we have a society in which the only tolerance we have in terms of medical device performance is perfect performance—it’s an impossible standard. We have to realize that there’s always risk involved with a device. You’re running into a bit of a clash between risk and realities,” noted Daniel Pelak, president and CEO of Research Triangle Park, NC-based Inner Pulse. By the same token, he said device manufacturers have a reponsibility to keep investing in their quality systems to reduce any unnecessary risk. "We have to remember these are lifesaving devices, and all quality systems have to make sure so that there's no chance for errors that could be caught early."
Weighing the Cost of Innovation: Companies Strive to Keep Profits Up in Challenging Circumstances
Given the high cost involved with developing, manufacturing and marketing new medical devices, it’s no surprise that manufacturers in the cardiovascular segment are always on the lookout for solutions that can reduce financial burdens. With the cost of healthcare rising every year, payers such as the Centers for Medicare and Medicaid Services (CMS) have developed more stringent standards a new product must meet before gaining approval for reimbursement, and device manufacturers have had to rise to the challenges these standards present.
“Fifteen years ago, cost didn’t factor so much into the decision tree, but now it’s high up there,” said Daniel Pelak, president and CEO of Inner Pulse in Research Triangle Park, NC. “There’s clearly a discernable difference now around cost in terms of technology development.”
Bruce Lindsay, MD, president of the Heart Rhythm Society, agrees. “Throughout medicine, at a time of rising cost—due to ,a large extent, sophisticated technology—we have to look at how we use technology and use it judiciously so we don’t increase cost of care,” he said. “As more technology comes along that makes us do procedures better, we’ll have to look at the benefits and make sure it’s worth the cost.”
Mike Howe, innovation manager for Creganna, a Galway, Ireland-based contract manufacturer (with US operations in Marlborough, MA), tackles the cost-containment challenge every day for customers. Older and new products alike are evaluated for lower-cost opportunities, but it’s the former category, he said, that often can achieve savings more easily. Maturing markets such as catheters, Howe explained, may not be evaluated so much for innovative designs these days as they are for designs that reduce costs.
“There’s always a niche for high-performance devices, but the workhorse devices usually can be achieved these days with a cost-effective design,” he added.
Just as cost containment is an issue from a reimbursement perspective, many companies that rolled out one innovation after another in the past couple of decades also are faced with the prospect of losing profits once their patents lose protection. Several manufacturers of angioplasty products, stents and other devices are going to lose their patent protection within the next five to 10 years, according to Howe, and device manufacturers will have to prepare for a wave of new competition as a result.
“You’re obviously going to try to keep innovating, but you still need a low-cost strategy for your workhorse products. Do you form a generic division in your company as a strategy, or just come up with a low-cost product? Someone needs to do some brainstorming by comparing other industries, such as pharmaceuticals, and compare to what they did there,” Howe said.
That said, the industry also would remain mindful of striking a balance between achieving cost savings and promoting the benefits of new technology in the grand scheme of healthcare.
“The biggest issue the medical device is currently facing is the misperception by some that medical technology is a significant contributing factor to the rising costs of healthcare,” said Stan Rowe, corporate vice president, Advanced Technology for Edwards Lifesciences, based in Irvine, CA. He pointed out that a recent study by Roland “Guy” King, former chief actuary at the CMS, showed only 6% of total national healthcare costs are related to medical technology and that the rate of increase for these costs is much less than the consumer price index. “It is important for the industry to increase awareness about the benefits of products in enhancing the quality of life for patients, improving quality and efficiency in the healthcare system and generating economic benefits and cost savings,” he concluded.