First introduced about two decades ago as a bailout technique for suboptimal or failed iliac angioplasty, peripheral vascular stenting gradually emerged as a valuable and versatile tool for a variety of primary and adjuvant applications outside the domain of coronary and cerebral vasculature. Today, peripheral vascular stenting techniques are commonly employed in the management of the most prevalent occlusive circulatory disorders and other pathologies affecting the abdominal and thoracic aortic tree and lower extremity arterial bed. Stents are also increasingly used in the management of the debilitating conditions like venous outflow obstruction associated with deep venous thrombosis and chronic venous insufficiency.
Notwithstanding a relative maturity of the core technology platforms and somewhat problematic opportunities for conversion to value-adding peripheral drug-eluting systems, peripheral vascular stenting appears to have a significant room for qualitative and quantitative growth both in established and emerging peripheral indications.
A panoply of stenting systems are available for the management of occlusive disorders and other pathologies affecting peripheral arterial and venous vasculature. Systems include lower extremity bare metal and drug-eluting stents for treatment of symptomatic PAD and critical limb ischemia resulting from iliac, femoropopliteal and infrapopliteal occlusive disease; stent-grafting devices used in endovascular repair of abdominal and thoracic aortic aneurysms; as well as a subset of indication-specific and multipurpose peripheral stents used in recanalization of iliofemoral and iliocaval occlusions resulting in CVI.
In 2015, these peripheral stenting systems were employed in approximately 1.565 million revascularization procedures worldwide, of which the lower extremity arterial stenting accounted for almost 1.252 million interventions (or 80.9%), followed by AAA and TAA endovascular repairs with 162.4 thousand interventions (or 10.5%) and peripheral venous stenting used in an estimated 132.6 thousand patients (or 8.6% of the total).
The U.S. clinical practices performed almost 528 thousand covered peripheral arterial and venous procedures (or 34.1% of the worldwide total), followed by the largest Western European states with over 511 thousand interventions (or 33.1%), major Asian-Pacific states with close to 377 thousand interventions (or 24.4%), and the rest-of-the-world with about 131 thousand peripheral stent-based interventions (or 8.4%).
Below is illustrated the global market for peripheral stenting by region in 2016 and by segment from 2014 to 2020.
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)
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.
The market for stents used in peripheral vascular indications — inclusive of stent grafts, and arterial and venous stents — is growing at an aggregate 6.2% CAGR from 2016 to 2020, which belies much stronger growth in specific subsets, especially in emerging markets like Asia/Pacific.
The aggregate compound growth rates for peripheral stent markets in each global region is shown below, with growth rates weighted by individual segment sales:
Western Europe: 5%
Rest of World: 13.9%
Peripheral stent products include the following, each of which is growing in sales at varying rates above and below the aggregregate regional sales growth:
Peripheral Arterial Stenting
– Bare Metal Stent Devices
– Drug Eluting Stent Devices
Aortic Aneurysm Repair
– Abdominal AA Stent-Grafts
– Thoracic AA Stent-Grafts
Peripheral Venous Stents
Worldwide Peripheral Stent Market by Product Category, 2015 and 2020
In a relatively classic scenario, established technologies have seen a loss of their once-premium pricing while emerging technologies are able to command an increasing premium as reward for their sophistication.
The worldwide coronary stent market is following the predicted course. Bare metal stents have been on the market for more than a decade and have, for six years, been overshadowed in the market by their more sophisticated drug-eluting competitor. The prices for these products have already bottomed out, with additional price erosion coming as a result of the general and sustained pressure on medical product prices.
The high prices commanded by drug-eluting stents have seen, and will see, a steeper decline as a result of increased competitiveness among market participants, the general downward pressure on prices for all medical products and, more significantly in the near-term, the advent of a new stent variant, the bioabsorbable stent.
Bioabsorbale stents are poised to command the prices once claimed by drug-eluting stents, due to their ability to further improve on outcomes in maintaining lumen patency, avoiding the need for repeat interventions and minimizing the likelihood of late stage thrombosis or other complications of stents.
The great unknown in the chart above is the impact of healthcare reform, the trend in medtech investment and the degree of severity in pricing pressures over this period. However, we anticipate that many or most of the initial, most significant effects of these forces will be felt in the 2010-2012 time frame. It may then only be the starting point (up or down) at which the above trends play out.
MedMarket Diligence has published, "Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017." See link.
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.)
* * * See the December 2015 report, “Global Market Opportunities in Peripheral Arterial and Venous Stents, Forecast 2020”. A $500 advance discount is available until publication. details * * *
A steady rate of technology development in coronary stents, producing an equally steady stream of new stent market introductions, is focused on expanding aggregate stent caseload (through penetration of what would otherwise be coronary artery bypass caseload) or shifting the balance even further toward concentration of stents sales to the drug-eluting stent (DES) variety. While unit volumes are on the rise, pricing pressures have dampened this overall market growth and will continue to put a squeeze on stent margins. This trend has been in force for the past two years (since the late stage thrombosis scare subsided), but going forward there will be more significant forces and developments impacting the stent market, principally the emergence of novel stent technologies like bioabsorbable stents, the emergence of drug-eluting balloons and the development of other anti-restenosis or anti-atherosclerosis options. These dynamics are the focus of the MedMarket Diligence report #C245, the post below being a brief excerpt from that report.
The evolution of the coronary stent market 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
Source: MedMarket Diligence report #C245, “Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017.”
Some novel stent technologies are under development by: AdvanSource Biomaterials, Allvivo Vascular, Inc., Blue Medical Devices, CeloNova BioSciences, Hexacath, InspireMD, ITGI Medical Ltd., Miami Cardiovascular Innovations (MCVI), MoBeta, Inc., Nexeon MedSystems, Inc., OrbusNeich, Palmaz Scientific, and Prescient Medical. Other technology developments in coronary artery disease treatments, beyond stent technologies, are also addressed in report #C245.
The improvements in stent flexibility and biocompatibility have lead to the conclusion by Dr. Mitchell Krucoff that second-generation drug eluting-stents, such as Abbott's Xience stent, result in an improved ability to prevent restenosis following angioplasty and stent implantation. See an excerpt from India's pharmabiz.com (which also highlights the market potential for coronary stents in India):
Newer drug eluting stents (DES) are proving to be significantly more effective and safer compared to the 'first-generation' drug eluting stents. DES is developed to reduce incidents of re-blockage or restenosis which occur with bare metal stents and almost all trials showed a marked reduction in restenosis rates. The ideal drug eluting stent is one which demonstrates high efficacy while maintaining excellent safety profile. The latest stents made of polymer and steel are known for higher biocompatibility. These are thinner in appearance and more flexible. The lower doses of the drug are much preferred as a long treatment option for complex and difficult cases. Another big advantage is the negative side effects. The drug eluting stents reduced the need for a second intervention procedure by about 40 to 50 per cent compared to bare metal stents especially in complex cases where patients reported long blockages in diabetics and those having small blood vessels, according to Dr Mitchell Krucoff, interventional cardiology scientist and advisor to US FDA on medical devices. See more at link
The global market for stents in the treatment coronary artery disease, while dominated by drug-eluting stents, continues to also be comprised of a diversity of stent technologies. The market is evolving steadily as manufacturers aggressively seek optimal anti-restenosis, characterized by the goal of low rates of repeat revascularization.
As with many medical technologies, prices, availability in different geographies and other factors also support the range of stent alternatives, leaving opportunity for stent types along the continuum of technology types and maintaining competitiveness in the stent market. Moreover, anti-restenosis is a goal of angioplasty that may also include a new twist, drug-eluting balloons.
(One must also keep in mind that cardiovascular surgeons will not lightly give up caseload in coronary artery bypass graft, with minimally invasive approaches and long term outcomes of CABG still putting up a strong challenge to coronary stents.)
Below are shown the major stent alternatives in the coronary stent market, with examples.
Types of Coronary Stents and Selected Anti-Restenosis Devices
Source: Report #C245, "Worldwide Market for Coronary Stents, 2009"
Coronary stent technology development trends include the stimulation of vessel wall healing following revascularization.
OrbusNeich has developed its "Genous", a patented endothelial progenitor cell (EPC) capture technology designed and shown to promote the accelerated natural healing of the vessel wall following stenting.