The Evolution of Coronary Revascularization Markets

Coronary artery bypass grafting (CABG) is the most common type of cardiovascular surgical intervention, which “bypasses” acute or chronic coronary artery obstructions via a newly created vascular conduit and thus reinstate normal or sufficient blood flow to the ischemic but still viable areas of the myocardium.

The majority of CABG surgeries (up to 75%) are still performed on the fully arrested heart which is accessed via a foot-long incision over the sternum and completely separated patient’s rib cage. Following a full sternotomy, the CABG patient is typically placed on extracorporeal cardiopulmonary bypass (CPB) with a heart-lung machine, which allows the surgeon to operate on a still and bloodless field. Simultaneously, the patient’s greater saphenous vein or internal mammary artery, or both are harvested (mobilized) for use as a bypass conduit in the ongoing procedure. Depending on the location, character and number of the coronary artery occlusions, the surgery might involve between one and seven coronary bypasses.

Once the bypasses are completed, the heart is restarted and, if it functions normally, the patient is removed from the heart-lung machine and the chest is closed up, the sternum is stabilized with stainless steel wire, and the chest and leg wounds are closed with sutures or clips. Patient’s recovery from a routine uncomplicated CABG usually involves seven to ten days of hospital stay, including two to three days spent in the cardiac intensive care unit.

Less Invasive CABG

Over the past decade, several less-invasive versions of the CABG were developed with the view of reducing morbidity and potentially serious complications associated with extensive surgical trauma and the use of aortic clamping and CPB. The current arsenal of less-invasive coronary artery bypass techniques includes minimally-invasive direct CABG (MIDCAB), full-sternotomy “off-pump” CABG (OPCAB), port-access CABG (P-CAB) with peripheral cannulation and endoclamping of aorta, and endoscopic computer (robotics)-assisted CABG (C-CAB).

Designed to limit surgical trauma of conventional CABG, the MIDCAB procedure is best suited for patients with occluding lesions either in the left anterior descending (LAD) artery, or the right coronary artery (RCA). In contrast to conventional CABG, it is performed on a beating heart without the use of CPB. In MIDCAB surgery, access to targeted arteries is achieved through a limited left anterior thoracotomy in the case of occluded LAD, and right thoracotomy or limited lateral thoracotomy in cases involving diseased proximal RCA or circumflex artery. Because of the smaller surgical trauma and off-pump performance (without aorta clamping), the MIDCAB procedure typically results in fewer complications, lower morbidity and shorter hospital stays compared to conventional CABG. However, its utility is limited to a subset of patients with one or two coronary vascular targets, which constitute a small fraction (<3%) of the total caseloads referred for CABG.

The OPCAB procedure is performed on a beating heart after reduction of cardiac motion with a variety of pharmacological and mechanical devices. These include slowing the heart rate with ß-blockers and calcium channel blockers and the use of special mechanical devices intended to stabilize the myocardium and mobilize target vessels. The use of various retraction techniques allows to gain access to vessels on the lateral and inferior surfaces of the heart. Because the OPCAB technique also involves surgical access via median sternotomy, its primary benefit is the avoidance of complications resulting from the use of cardiopulmonary bypass, not surgical trauma.

Over the past decade, the OPCAB surgery emerged as the most popular form of less-invasive coronary artery bypass procedures in the U.S, and Western Europe. By the beginning of this decade, an estimated 25% of all CABGs performed in these geographies were done without the use of CPB. However, in recent years, the relative usage of OPCAB techniques remained largely unchanged. In the view of many cardiac surgeons, the latter was predicated by the increasing morphological complexity of cases referred for CABG (rather than PCI) and generally superior immediate and longer-term bypass graft patency and patient outcomes obtainable with technically less-demanding on-pump CABG surgery.

In contrast to that, the relative usage of “neurological complications sparing” OPCAB techniques is significantly higher in major Asia-Pacific states reaching over 60% of all CABG procedures in China, India, and Japan.

The rarely used P-CAB procedure involves the use of cardiopulmonary bypass and cardioplegia of a globally arrested heart. Vascular access for CPB is achieved via the femoral artery and vein. Compared to the MIDCAB technique, the use of multiple ports allow access to different areas of the heart, thus facilitating more complete revascularization, and the motionless heart may allow a more accurate and reliable anastomosis. In distinction from conventional CABG, median sternotomy is avoided, which reduces trauma and complications. However, potential morbidity of the port-access operation includes multiple wounds at port sites, the limited thoracotomy, and the groin dissection for femoral-femoral bypass. The procedure is also technically difficult and time consuming and therefore has not achieved widespread popularity.

The Hybrid CABG-PCI procedure combines the use of surgical bypass (typically MIDCAB) and percutaneous coronary interventional techniques (angioplasty and stenting) for optimal management of multi-vessel coronary occlusions in high risk patients. The main rationale behind the utilization of hybrid procedure is to achieve maximally possible myocardial revascularization with minimally possible trauma and reduced probability of post-procedural complications. The most common variation of the hybrid revascularization involves MIDCAB-based radial anastomosis between the left anterior descending artery and left internal thoracic artery accompanied by the PTCA/stenting-based recanalization of less critical coronary artery occlusions.

CABG Utilization Trends and Procedure Volumes

Since the advent of coronary angioplasty in the late 1970s, the relative role and share of CABG procedures in myocardial revascularization have been steadily declining due to a continuing penetration of treated patient caseloads by a less invasive PTCA. This general trend was further expedited by the advent of coronary stents. At the very end of the past decade, the rate of transition towards percutaneous coronary interventions in myocardial revascularization started tapering off, primarily due to growing maturity of PTCA/stenting technology and nearly full coverage of patient caseloads with one- or uncomplicated two-vessel disease amendable through angioplasty and stenting. At the same time, a growing popularity of the less-invasive CABG regimens resulted in some additional influx into CABG caseloads from a no-option patient cohort. A less-invasive surgical coronary bypass also emerged as a preferred treatment option for some gray-area patients that were previously referred for sub-optimal PTCA and stenting to avoid potential complications of conventional CABG.

In 2006 – for the first time in about two decades – the U.S. and European volumes of CABG procedures experienced a visible increase, which was repeated in 2007 and reproduced on a smaller and diminishing scale in the following two years.

The cited unexpected reversal of a long established downward procedural trend reflected an acute (and, probably, somewhat overblown) end-users’ concern about long-term safety (AMI-prone late thrombosis) of drug-eluting stents (DES), which prompted a steep decline in utilization of DES in 2006, 2007, followed by a smaller and tapering decreases in 2008 and 2009 with corresponding migration of advanced CHD patients referred for radical intervention to bare metal stenting and CABG surgery.

In 2010 – 2015 the volume of CABG surgeries remained relatively unchanged, notwithstanding a visible decline in percutaneous coronary interventions and overall myocardial revascularization procedures.

In the forthcoming years, the cumulative global volume of CABG procedures is unlikely to experience any significant changes, while their relative share in coronary revascularization can be expected to decline from about 15.4% in 2015 to roughly 12.3% by the end of the forecast period (2022). The cited assertion is based on the expectation of eventual stabilization and renewal of nominal growth in utilization of PCI in the U.S. and Europe coupled with continuation of robust expansion in the usage of percutaneous revascularization techniques in Asia-Pacific (especially India and China, where PCI volumes were growing by 20% and 10% annually over the past half decade, according to local healthcare authorities).

In 2016, the worldwide volume of CABG surgeries leveled at approximately 702.5 thousand procedures, of which roughly 35.2% involved the use of less-invasive OPCAB techniques. During the forecast period, the global number of CABG procedures is projected to experience a nominal 0.1% average annual increase to about 705.9 corresponding surgical interventions in the year 2022. Within the same time frame, the relative share of less-invasive bypass surgeries is expected to register modest gains expanding to approximately 36.7% of the total in 2022.

Coronary Revascularization Procedures, 2015-2022 
(Figures in thousands)

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CABG and Primary PCI in Coronary Revascularization to 2022.

In, “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022”, Report #C500, we forecast cardiovascular procedure utilization, caseload, technology trends, and device market impacts, for the U.S., Western Europe, Asia/Pacific, and Rest of World.

Dyslipidemia therapy takes a step forward

In medical technology development, there are perennially long-shot technologies being pursued for their ability to make an order of magnitude shift in treatment.  This, of course, seems to be the thrust of a majority of biotechnology development, which seeks to provide cures where only palliative treatments (drug or device) currently exist, such as in gene therapy and stem cell therapy.  

But on a more practical level (i.e., well within the next ten years), examples include non-invasive blood glucose monitoring in diabetes, the development of effective dyslipidemia therapy and others.  On that note, the development of Esperion Therapeutics' ETC-1002 took a step forward this past week, with the commencement of a Phase I clinical trial of the drug.

Dyslipidemia therapy, as its name connotes, is an approach to treating coronary heart disease not by coronary bypass, angioplasty or any physical device treatment to remove atherosclerotic plaque from clogged arteries, but by targeting the underlying metabolism of lipids that has produced those plaques, with the ultimate goal of reducing plaques non-invasively. 

An effective non-invasive treatment of atherosclerosis poses a significant threat to palliative treatments.  It may be a bit cliche to reduce the argument to the attractiveness of taking a pill instead of undergoing surgery, but that scenario is not far from the truth. Such a prospect puts the entire industry of device treatments for coronary artery disease (CAD) on notice.

For the time being, coronary stents still represent one of the best minimally invasive avenues for patients with CAD.  (See our report.)

Coronary stent market opportunity

Stenting is not ideal for all patients with coronary heart disease, such as those with left main or three (or more) vessel disease. However, the vast majority of cardiovascular disease patients can benefit from the benefits of PCI, not the least of which include a shorter recovery period and less trauma to the patient.

The global market for coronary stents is over $7 billion and growing steadily. With the average age of citizens in developed countries increasing, there is an increased need to provide medical care to the average citizen. As such, an aging population translates into increasing numbers of people needing medical therapy and increasing numbers of people who need more aggressive medical therapy due to the aging process. As the population of developed countries ages, the number of percutaneous coronary interventions (PCIs) required increases as well. Currently, the incidence of PCI procedures (sometimes referred to as percutaneous transluminal coronary intervention or PTCA) is increasing at a rate of 3%–5% worldwide. Today, the vast majority of PCIs involve the implantation of one or more coronary stents.

Until the advent of coronary stents, patients with cardiovascular blockages had little choice but to either keep a close eye on their disease (“watchful waiting” with or without accompanying pharmaceutical therapy) or undergo coronary artery bypass grafting (CABG). When angioplasty was developed by Andreas Gruentzig in 1977, patients were presented with the option to undergo angioplasty in an effort to open blocked coronary arteries. While short-term benefits were usually seen with balloon angioplasty, longer-term outcomes showed many arteries re-closing and requiring repeated intervention; up to 50% of angioplasty patients were found to require further angioplasty within six months. In an effort to reduce the frequency of patients requiring reintervention, scientists and clinicians developed stents that could be left behind to hold the artery open once the PTCA balloon was withdrawn.
Unfortunately, clinicians found that bare metal stents (BMS) could cause an immunological response that would try to “protect” the body from the foreign material (i.e., the stent). This, in turn, would lead to further narrowing near to or inside the stent, as seen in roughly 25% of patients receiving BMS devices. To combat this, drug-eluting stents (DES) were developed. 

Drug-eluting stents were developed to release a drug (e.g., sirolimus or paclitaxel) intended to reduce the incidence of restenosis. From there, even more innovative products have been developed, such as bioactive stents or stents designed to attract a patient’s own endothelial cells to coat the stent (as in devices by OrbusNeich, Hexacath, and Miami Cardiovascular Innovations).

Other device developers have sought to create stents that will fully degrade and disappear over a period of weeks or months—of a score of companies in this area, Abbott Vascular, Biotronik and REVA Medical appear closest to market. Yet others seek to abandon the use of stents altogether, opting instead to pursue an angioplasty balloon that will leave the anti-inflammatory drugs behind without the accompanying stent, as with CE Mark approved devices by EuroCor (the DIOR catheter) and B. Braun Melsungen (the SeQuent Please catheter).

Because the ultimate therapy has not yet been found, many opportunities still exist for effective therapies to combat atherosclerosis. So far, coronary stents hold the most promise for effectively treating an aging population with an increasing incidence of coronary artery disease.


See also, "Worldwide Coronary Stent Market, 2008-2017" at link.

Growth of coronary stent market in Japan, China

(The global market for coronary stents worldwide is assessed in the MedMarket Diligence report #C245, "Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017.")

japan-china-stentsThe market for coronary stents in Asia and the Pacific region contains both China (early technology adopters) and Japan (with a longer regulatory approval cycle), which generated a combined majority of stent sales from the region. The Asia/Pacific market for coronary stents is forecasted to grow 6.7% annually over the period from 2008 to 2017.

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In terms of stent type, the Asia/Pacific market is dominated by drug-eluting stents, which represent roughly 80% of the market—a much larger portion of the stent market than seen in other regions. This is due to the fact that in China, nearly 100% of coronary stents used are drug-eluting. The remaining 20% of the market represented by bare metal stents are largely in those areas outside China.

The introduction of bioabsorbable stents will increase the total market for coronary stents and reduce the dominance of "non-bioabsorbable" drug-eluting stents in the market, although (as we have implied) a share of bioabsorbable stents will be of the drug-coated variety.


Data sourced from MedMarket Diligence Report #C245 (published 2Q 2009).

Coronary stents: Big differences in adoption globally

Market drivers that vary geographically account for some big differences in the distribution of the coronary stent market across the currently available stent types, and these differences will continue when bioabsorbable stents (and others) are introduced to the market over the next few years.

The local market forces dictating these differences include:

  • Regulatory timelines in one market that can delay new product introductions by a year or more compared to another market
  • Regulatory control that either limits or facilitates introduction of local market ("me too") stent developers.
  • Differences in clinical adoption of advanced technologies driven by local practice patterns
  • Price sensitivities that can vary considerably from one geography to the next, with the potential to severely restrict the adoption of advanced technologies and/or force price reductions

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The coronary stent market illustrated distinct differences in market segmentation on the basis of geography, challenging assumptions of the expected market shares of current and potential stent manufacturers competing in each local market.  One of the most distinct differences is the relative adoption of drug-eluting stents in China (captured in Asia/Pacific, below) versus either the U.S. or Europe. 

Source: MedMarket Diligence, LLC.  Report #C245, "Worldwide Coronary Stent Market, 2008-2017."

What medtech company isn’t globally focused?

My posts on advanced medical technology, drawing frequently from our market reports, are worth emphasizing for their global perspective.  Some two decades ago, it became apparent to me that that the global market perspective is not reserved for big, multi-national companies and their global presence.  My understanding of this came about from the experience of seeing clients of all sizes showing their interest — their compelling need — to examine markets outside the U.S.  Whether trends like the formation of the European Union and the easing of trade across its member states’ borders, the odd appearance of market economies under Communist China, the economic development of democratic states in South America or even the emergence of newly accessible markets in Eastern Europe — too many changes were making it such that medium or even small sized companies could not overlook opportunities beyond their domestic borders.

Now, I would find it rather striking to see a company focusing its efforts on only one country.  As a corollary, I find it equally striking that some market analyses are still peddled that focus only on specific countries.  Certainly, I understand the somewhat misguided incentive to do so — it’s easier to focus on one country, one set of patient demographics, one set of regulatory challenges. 

Yet, for the cost of product development, the consistent demand by patients for therapeutic outcome regardless of where they live, the available channels to get products into new countries, the ease with which competitors’ innovations will make it cross-border — it simply makes no sense to focus on one particular market.

So I rarely find the need among savvy clients to pressure them into broadening their perspective.  They have already long since reinforced the premise, to me, that the information they seek on medical markets is not complete unless it considers the global perspective. 

Because if they don’t get a good handle on global markets, they will promptly lose advantage to their competitors.

In the coronary stent market, many preconceived notions miss the mark

The coronary stent market has represented a marvelous opportunity for many medical technology companies, but even though it is a huge market now, and has generated enormous cash flow for early entrants, it runs significant risk for current manufacturers as well as those seeking to gain share of this multi-billion dollar global market.  The reason is that preconceived notions tend to be strong in this market.  There are several such notions that either aren’t well represented by recent trends or may be flat out wrong:

·         Bare metal stents will continue to hold a significant share of the coronary stent market due to lingering concerns over drug eluting stents

·         Drug-eluting stents have established themselves as unquestionably competitive with coronary artery bypass

·         The majority of coronary artery disease caseload will indefinitely be represented by angioplasty/stenting or coronary artery bypass grafting

·         Given clinical results, the opportunities for coronary stents are uniform across different geographies

·         Robotic, totally endoscopic coronary artery bypass (TECAB) and other advanced technologies to make bypass less traumatic and therefore more competitive with angioplasty/stenting may generate positive clinical results, but economics make them non-competitive

·         The nature of healthcare demand for coronary artery disease treatment will make this largely area price insensitive to the pressures of healthcare reform

·         Post-surgical restenosis has been adequately addressed by drug-eluting stents, creating a substantial hurdle for competitive anti-restenosis alternatives

Now, admittedly, some of you readers already know where some of the assumptions above have simply gone awry. However, it is striking that medtech markets are often characterized by slow recognition by the industry of the changing drivers and dynamics underpinning market success.

See report #C245, “Worldwide Drug-Eluting, Bare and Other Coronary Stents Market, 2009”.

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Coronary Stent Manufacturers Take Heed: Challenges Will Come from All Sides

In the $7 billion+ worldwide market for drug-eluting coronary stents, a consistent theme is now the myriad challenge to existing players from the host of emerging competitors, particularly since the advent of drug-eluting stents (DES). Although not so long ago the DES market was monopolized by J&J/Cordis, then split and controlled by J&J and Boston Scientific, those were the old days. The market is now being progressively divvied up by a crowd of DES manufacturers, and some, like Abbott, with its successful Xience stent, are giving J&J and Boston Scientific a real run for their money.

But the challenges for the DES market, which are significant enough in the emergence of many DES designs seeking clinical, cost and other competitive advantages, are not limited to DES competition. Angioplasty and stenting face a range of competitive challenges in the clinical management of coronary heart disease that force manufacturers to consider the advantages and limitations of DES and all of the alternatives. 

Minimally invasive coronary artery bypass grafting (MIDCAB, TECAB, etc.). The primary threat that DES posed to coronary artery bypass was that, with the dramatic reduction in restenosis offered by drug-eluting stents, a percutaneous procedure had outcomes that rivaled CABG (to varying degrees, depending upon whether you talked to a cardiac surgeon or an interventional cardiologist). Given a choice between sternotomy and femoral puncture (and associated recovery and cost), the cath lab procedure won out. However, the onus on surgical instrumentation manufacturers has been fully understood, such that various minimally invasive alternatives to traditional CABG are now dramatically narrowing the gap in trauma between angioplasty/stenting and CABG.

Irreversible electroporation for anti-restenosis. This technique, using very short electric field pulses to destroy cells in the intima, is yet unproven and still needs to be fit into an overall intervention, but nonetheless offers a potential alternative to drug-elution to prevent restenosis. Whether this technology (currently under development at Hebrew University of Jerusalem) succeeds in product approval and clinical development is less the issue than the fact that multiple technologies and approaches are being developed to target restenosis.

Atherosclerosis-reducing drugs (HDL therapy). There was great fanfare when Esperion Therapeutics’ drug, ETC-1002, demonstrated preclinical results indicating an ability to reduce atherosclerosis. The ability to sidestep the entire issue of needing to be less- or minimally-invasive by drug therapy represents a real challenge to not only stents but also bypass procedures.

Drug-eluting balloons. A handful of companies are developing drug-coated balloon catheters as an alternative to balloon angioplasty and stenting and for those who would not benefit from percutaneous procedures, such as those in whom antiplatelet therapy is neither recommended nor desired.

Late-stage thrombosis. The sudden threat, in 2006, that DES products might have a major drawback as a result of the formation of life-threatening clots was ultimately tempered by data indicating the threat was not as significant as feared. However, we remain in a period during which the clinical history of drug-eluting stents has yet to fully illustrate the risks of each of the approved drug-eluting stents on the market. Indeed, some competitors whose products show great promise may ultimately prove to have unforeseen flaws.

Competition in stent alternatives, for the time being, still represents the greatest challenge to competitors. The $7 billion worldwide coronary stent market creates big incentive for players to simply displace market share from other stent manufacturers. But if competitors do not keep in view the full breadth and depth of competition — from any source — they will face obsolescence sooner or later.

 

See the MedMarket Diligence report #C245, "Worldwide Coronary Stent Market, 2008-2017."

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Purchase for download:  Report #C245, "Worldwide Coronary Stents 2009, PDF" — $2,850.00
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Coronary stent innovations focused on expanded use, complications

The evolution of the coronary stent market, like most medical device markets, has been driven by manufacturers focused on expanding the use of coronary stents into new caseload as well as penetrating the market shares of competitors.  

Clinicians, for their turn as gatekeepers in this effort, are guided in the adoption of stent technologies by the availability of clinical evidence supporting expansion of stent use to patients whose coronary heart disease might otherwise be addressed by coronary artery bypass graft (CABG) surgery, with their selection of the specific stent used determined (to the extent that price is not an overriding attribute) by how well each stent’s clinical data stands up under scrutiny of possible clinical complications.

Manufacturers then take a hard view of both cost and complication rates.  Below are shown the potential complications ensuing from stent implantation and which have therefore become a focus of stent technology development:

Potential Complications Related to Implantation of Cardiovascular Stents

stent-complications

Source: MedMarket Diligence report #C245, "Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017."  


Purchase for download:  Report #C245, "Worldwide Coronary Stents 2009, PDF" — $2,850.00
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UCSF, Osiris start cardiac stem cell study for heart attack

Perhaps in no other market is it more imperative for current competitors to keep their eyes on the horizon than in the market for treatments of coronary artery disease. As I have ranted previously (search "coronary artery disease" on this blog), alternative treatments stretch from device to surgery to biotech and options too difficult to categorize. And the options continue to grow. In the biotech area, cell therapy has moved to human studies:

 

Researchers at UCSF Medical Center started enrolling patients in an early-stage adult stem cell therapy, developed by Osiris Therapeutics Inc., for first-time heart attack patients. (Continued at link.)

 

Currently, the majority of coronary artery disease treatments are captured by coronary artery bypass grafting ot angioplasty/stenting. These options are likely to remain the most used for some time, with technology development on both sides (bioabsorbable and other stents versus minimally invasive bypass, etc.), but manufacturers must keep their eyes open as clinical research extends on the horizon into non-surgical or even non-interventional options.

See the MedMarket Diligence report #C245 on "Coronary Stents Worldwide".

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Purchase for download:  Report #C245, "Worldwide Coronary Stents 2009, PDF" — $2,850.00
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