In 2016, the cumulative worldwide volume of the the following CVD procedures is projected to approach 15.05 million surgical and transcatheter interventions:
roughly 4.73 million coronary revascularization procedures via CABG and PCI (or about 31.4% of the total),
close to 4 million percutaneous and surgical peripheral artery revascularization procedures (or 26.5% of the total);
about 2.12 million cardiac rhythm management procedures via implantable pulse generator placement and arrhythmia ablation (or 14.1% of the total);
over 1.65 million CVI, DVT, and PE targeting venous interventions (representing 11.0% of the total);
more than 992 thousand surgical and transcatheter heart defect repairs and valvular interventions (or 6.6% of the total);
close to 931 thousand acute stroke prophylaxis and treatment procedures (contributing 6.2% of the total);
over 374 thousand abdominal and thoracic aortic aneurysm endovascular and surgical repairs (or 2.5% of the total); and
almost 254 thousand placements of temporary and permanent mechanical cardiac support devices in bridge to recovery, bridge to transplant, and destination therapy indications (accounting for about 1.7% of total procedure volume).
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.
Congenital heart abnormalities – which occur in an estimated 1.1% to 1.3% of infants born in the U.S. and worldwide each year – constitute leading cause of birth defect-related deaths. To-date, clinicians have identified and documented almost four dozens distinctive heart defects in newly born ranging from relatively simple and easily correctible abnormalities to complex and multiple anatomical malformations.
The most commonly encountered congenital heart abnormalities accounting for the majority of all diagnosed cases include: ventricular septal defect (VSD); tetralogy of Fallot (TOF); transposition of great vessels (TGV); atrioventricular septal defect (ASD); and coarctation of aorta (COA).
Selection of treatment protocols for congenital heart defects depends on the morphology of the abnormality and its immediate and long-term impact on cardiopulmonary function and patient’s prognosis (threat to survival).
Many asymptomatic patients with minor defects (typically representing unresolved inheritance from normal fetal development, such as trans-septal conduits that are supposed to close at birth) might be put on a “watchful waiting” regime.
Some symptomatic and functionally compromising congenital heart defects can be treated with minimally invasive percutaneous (transcatheter) techniques. To-date, percutaneous repair tools have been developed and clinically tested for several common congenital myocardial abnormalities including: patent ductus arteriosus (PDA), atrial septal defect, ventricular septal defect and patent foramen ovale (PFO). In all instances, the primary objective of the transcatheter approach was to reduce morbidity, mortality and costs associated with the procedure by achieving septal repair or closure via endovascular implantation of specially-configures occluding or sealing devices.
In cases involving complex, debilitating and life threatening congenital myocardial abnormalities (such as Tetralogy of Fallot, transposition of great vessels, etc.) one or several corrective open heart surgeries represent the only route to patient survival. Such surgeries are typically performed during the first year of infant’s life and carry a 5% risk of mortality, on average.
Source: MedMarket Diligence, LLC; Report #C500, “Global Dynamics of Cardiovascular Surgical and Interventional Procedures, 2015-2022.”
Based on the available industry data and MedMarket Diligence estimates, in 2015, approximately 387 thousand congenital heart defect repair procedures were performed worldwide, of which less invasive transcatheter interventions accounted for about 24.3% and open heart corrective surgeries for the remaining 75.7%.
For the period 2015 to 2022, the cumulative global volume of congenital heart defect repair procedures is projected to grow 1.9% per annum to approximately 444 thousand percutaneous and surgical interventions in the year 2022. The usage of transcatheter procedures can be expected to experience significantly faster 9.0% average annual growth (partially at the expense of corrective open heart surgeries for septal defects), reflecting mostly accelerated transition to minimally invasive percutaneous septal defect repair in APAC and ROW market geographies (where the latter techniques currently used only in 15% to 22% of corresponding procedures, compared to 60% to 75% in Western Europe and the U.S.).
With the FDA's approval of Medtronic's Melody Transcatheter Pulmonary Valve and Ensemble Delivery System (see link), another step has been made toward eliminating traditional surgery — at least that's the idea. The ability to implant a valve via a percutaneous procedure advances the art of less invasive intervention in ways akin to laparoscopic surgery, albeit at lower volume.
Percutaneous, NOTES (natural orifice transluminal endoscopic surgery) and laparoscopic surgery are progressively removing the need for invasive traditional surgery.
It is precisely due to percutaneous procedures that coronary stents have been able to present such a clinical challenge to coronary artery bypass. Although minimally invasive approaches to CABG are an attempt to pull back some surgical caseload, they are technically complex, expensive and, therefore, are not likely to stem the tide toward the dominance of percutaneous procedures. Ironically, the one procedure that may save bypass is the transcatheter route. With the approval of the Melody approach, it is clear that that is not impossible.
At the time, it was determined that, despite the clear concerns about the link between drug-eluting stents and late stent thrrombosis, it was demonstrated, at data presented at the 2008 TCT meeting, that the risk was actually minimal and, in any case, not sufficient to preempt the compelling benefits offered by drug-eluting stents.
Now, a small study at University Hospital at Bern, Switzerland, examining 28 patients, found a high correlation between the incidence of late stent thrombosis and hypersensitivity (evidenced by high eosinophil infiltrates) to the drug coating the stent or, more likely, the stent polymer, resulting in remodeling occurring around the stent struts. Such hypersensitivity is considered very rare — resulting in an incidence of MI or death that is no higher than for bare metal stents, making it a non-issue in the market for DES versus bare metal stents.
MedMarket Diligence has completed a global analysis of the drug-eluting, bare metal and other coronary stents market. See report C245 for details.
The market for coronary stents in Europe is estimated at nearly $2 billion and forecast to grow to more than $3 billion by 2017 for a growth rate of 5.4% annually. The breakdown by type of coronary stent shows drug-eluting stents dominating the market, and continuing to grow. Â The aggregate market in Europe will also grow in accordance with growth in percutaneous coronary interventions, as well as in association with the anticipated introduction of absorbable coronary stents in the 2013 timeframe. Â Due to growth in drug-eluting stents and the introduction of absorbable stents, the relative share of bare metal stents will progressively decline.
In late 2009, Boston Scientific is expected to launch its Promus Element stent in Europe, a new stent design coated with everolimus. The potential exists for the Promus Element to impact Abbott/Xience market share. However, Abbottâ€™s launch of the next-generation Xience in Europe should help counteract most negative effects of the Promus Element launch.
The use of stents is ideal for all patients with coronary heart disease with the exception of patients with left main or three (or more) vessel disease. 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 estimated to be in excess of $7 billion and currently growing at 5%–6% per year. 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.
The global market for stents in the treatment of coronary artery disease is the subject of the May 2009 MedMarket Diligence report #C245, "Worldwide Market for Drug-Eluting, Bare and Other Coronary Stents, 2008-2017."
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.
The trend in the development of coronary stents and their associated market segments is for price pressure but continued sales growth in drug-eluting stents, persistent utilization of bare metal stents driven by their lower prices and the emergence within a few years of bioabsorbable/biodegradable stents, which will raise the bar on stent performance, even compared to drug-eluting stents.
The growth versue market size bubbles for unit volume sales of the three stent types in 2014 are shown below.
Source: MedMarket Diligence, LLC; Report #C245, "Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017."
The evolution in development of devices for anti-restenosis in treatment of coronary artery disease (for the time, limiting the focus to the various types of coronary stents) has proceeded along a path from the development of a device to maintain patency after angioplasty, then further reduce the occurrence of restenosis (which was occurring even in the presence of stents), to further reducing stents’ potential to induce restenosis despite the advanced stent shapes, drug coatings and other features.
The main categories of stent types reflecting this development timeline are (1) bare metal stents, (2) drug-eluting or drug-coated stents and, soon to come, (3) absorbable stents. Within and between these categories, there are multiple variations in designs from the stent materials, stent shapes, stent coating types, stent coating methods and other differences.
Currently, drug-eluting stents dominate the coronary stent landscape worldwide. While price pressures have been pushing back on the premiums of these devices, their efficacy compared to bare metal stents or, more significantly, coronary artery bypass, have enabled a very healthy unit volume growth rate. Drug-eluting stents continue to increase in unit volume and caseload as clinicians opt for their use over the "restenosis-challenged" bare metal stents and the highly traumatic coronary artery bypass.
Treatments for coronary artery disease have demonstrated a dramatic tendency to evolve, driven by the high incidence of heart disease, its acute nature and the robust, enabling technologies in the use of drug-coatings and the emergence of advanced materials technologies, which have moved development toward the next phase of stent development, which is absorbable/biodegradable stents. As quoted by Dr. Patrick Serruys at CRT 2007, “Abolition of neointimal hyperplasia is no longer the ultimate goal. Development of more biocompatible and bioabsorbable stents facilitating adequate endothelialization is expected in the near future.”
Below is the current (2008) and the 2017 distribution of unit volumes for the major types of drug-eluting coronary stents.
Considering all of the different businesses, areas of clinical focus or types of products to market/sell that are among options open to medtech manufacturers, one would have to look at coronary stents as a pretty attractive market.
The worldwide market for coronary is at around $7.4 billion, with emerging growth in select segments at double-digit rates over the next five years.
Coronary artery disease remains a prevalent disease with high enough annual incidence to sustain the coronary stent market (and other revascularization technologies) for years to come.
There are only a few significant competitors in this market, and while there may be many in the wings looking to enter, the market is still ripe for novel technologies that demonstrate clinical efficacy.
The framework for the introduction of even a potentially radical new stent technology is well established. Interventional radiology is a high volume practice, with a large population of experienced clinicians delivering stent technology to patients. Unless a new stent design demands a radically different deployment method, and clinical data is otherwise strong for safety and efficacy, clinical adoption should not be a problem.
While there is plenty of discussion about the FDA scrutinizing the 510(K) process, and this does raise a cautionary flag, the worst case scenario would be that stents would have to provide additional data than has been required in the past.
Although stents are small, there are opportunities for multiple participants in an individual stent’s design and construction, from the metal, polymer or other material used, the coating(s) used, the coating process or other elements. (For example, the paclitaxel drug-eluting stent technology behind the successful TAXUS stent of Boston Scientific was developed by Angiotech.)
As we note in our Report #C245 on coronary stents, there are numerous technologies for revascularization of coronary arteries, with new stent and other technologies under development. Coronary stents nonetheless remain a dominant option with good staying power.
Consider the alternative medtech opportunities, given regulatory, reimbursement, cost, R&D and other hurdles, and it is reason enough for there still to be opportunities in the coronary stents business.