Cardiovascular diseases (CVDs) are a variety of acute and chronic medical conditions associated with an inability of the cardiovascular system to sustain an adequate blood flow and supply of oxygen and nutrients to organs and tissues of the body. The CVD conditions may be manifested by the obstruction or deformation of arterial and venous pathways, distortion in the electrical conducting and pacing activity of the heart, and impaired pumping function of the heart muscle, or some combination of circulatory, cardiac rhythm, and myocardial disorders.
These diseases are treated via the following surgical and interventional procedures:
Coronary artery bypass graft (CABG) surgery;
Coronary angioplasty and stenting;
Lower extremity arterial bypass surgery;
Percutaneous transluminal angioplasty (PTA) with and without bare metal and drug-eluting stenting;
Peripheral drug-coated balloon angioplasty;
Surgical and endovascular aortic aneurysm repair;
Vena cava filter placement
Mechanical venous thrombectomy;
Venous angioplasty and stenting;
Carotid artery stenting;
Cerebral aneurysm and AVM surgical clipping;
Cerebral aneurysm and AVM coiling & flow diversion;
Left Atrial Appendage closure;
Heart valve repair and replacement surgery;
Transcatheter valve repair and replacement;
Congenital heart defect repair;
Percutaneous and surgical placement of temporary and permanent mechanical cardiac support devices;
In 2016, the cumulative worldwide volume of these procedures is projected to approach 15.05 million surgical and transcatheter interventions. This will include:
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).
Below is illustrated the overall global growth for each of the major categories of procedures through 2022.
There is considerable variation in the growth of cardiovascular procedures globally, but most growth is coming out of Asia/Pacific. For example, within the area of venous interventions, the growth in the use of endovenous ablation for chronic venous insufficiency is markedly higher in Asia/Pacific than in other regions, though the U.S. will remain the largest volume of these procedures.
“Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022” (Report #C500), published August 2016. See description, table of contents, list of exhibits at link. Available for purchase and download from link.
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.
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.
Because of the invasive nature of cardiac surgery, medical therapy will always be the preferred treatment protocol favored by many clinicians. To that end, device and pharmaceutical manufacturers continue to explore methods of treating atherosclerosis that will render surgery unnecessary.
For instance, researchers at the Medical University of Graz in Austria announced in February 2009 (Journal of Lipid Research, 50:312-326) progress related to their study of a synthetic atherosclerosis drug that can reduce the build-up of plaque without producing the side effect of fatty liver disease, which can lead to other disorders such as diabetes. However, in some instances, more aggressive therapy is required and for those patients, there is a host of therapy choices available — all of which can prove to be competitive with stenting technology.
The range and diversity of alternatives for treatment of acute coronary artery disease are striking:
angioplasty with or without stenting
coronary artery bypass grafting
MIDCAB (minimally invasive direct coronary artery bypass)
RACAB (robotic assisted coronary artery bypass)
transmyocardial laser revascularization
nanoparticles and other agents
While the caseload distributed across these alternatives is concentrated in angioplasty (with stenting) and coronary artery bypass grafting, the acute nature of coronary artery disease, the size of the caseload and the continued pressure on clinicians to reduce the associated trauma of treatment give incentive to developers seeking to produce better outcomes.
The MedMarket Diligence report #C245 is described at http://mediligence.com/rpt/rpt-c245.htm and details the worldwide market for the use of alternative stent devices in the treatment of coronary artery disease. The report assesses the treatment of coronary artery disease by alternative treatment methodologies (percutaneous intervention with or without stenting, coronary artery bypass grafting alternatives and other medical/surgical treatment options), with estimated current/forecast caseload across treatment types.
The report is described at this link. The report may be ordered for immediate download online.
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"
PRLog (Press Release) – Sep 09, 2009 – The global market for coronary stents is owned largely by drug-eluting stents (DES), but the size of the patient pool, the drive for lowered cost, ever-increased efficacy and less trauma are spawning the development of multiple new technologies in coronary stents and competitive anti-restenosis technologies. The global market, products, companies, trends and opportunities are the subject of the 2009 report, "Worldwide Coronary Stents 2009," from MedMarket Diligence
Translation: Drug-eluting stents are to bare metal stents as bare metal stents were to percutaneous transluminal coronary angioplasty alone.
In the September 1 post on the meta-analysis by researchers at Tuft Medical Center, we noted the overall findings in general terms of the value of drug-eluting stents compared to bare metal stents. It is worthwhile to provide the slightly more detailed conclusions of the authors:
"As a new technology, drug-eluting stents have now emerged as an important innovation in reducing coronary restenosis. To provide a precise estimate of their clinical benefit and to explore sources of statistical heterogeneity, we performed a meta-analysis of randomized controlled trials involving currently available drug-eluting stents using a DerSimonian and Laird random effects model. Our meta-analysis found no significant reduction in mortality or MI-free survival from the use of drug-eluting stents. However, drug-eluting stents clearly reduced the risk of restenosis by 23% and the risk for target lesion revascularization by 11% in the primary analysis. This is similar in magnitude to the benefit found for stents compared to balloon angioplasty. The need for revascularization after DES was 3.7% that is similar to the 3.8% observed after coronary artery bypass grafting and much lower than the 21% with bare-metal stents."
I have engaged in debate (I might actually call it "baiting") wtih those who have instead favored coronary artery bypass graft (CABG) surgery, which I view as a waning procedure compared to percutaneous methods (like angioplasty with stenting) that revascularize with minimal trauma to achieve clinically competitive outcomes. I would argue that the most minimally invasive procedure is ultimately likely to resemble a percutaneous one anyway. Indeed, if one were to project the future evolution of CABG, it would traverse a course from thoracotomy to endoscopy (thoracoscopy) to an intraluminal procedure (which garners negative feedback from surgeons; but, of course, when speaking with surgeons, I expect their answers to be geared toward the scalpel).
By comparison, drug-eluting stents are on a course toward an analogously less invasive option, which I envision as first, atherosclerosis-reducing drugs and, probably ultimately, gene therapy that preemptively addresses the incidence of atherosclerosis. Right now, that is fantasy, but not by much.
See also the MedMarket Diligence report #C245 on the global market for coronary stents.
The global coronary stent market faces continued growth, development and competition from a wide range of technology types and competitors. The market is detailed in a new report from MedMarket Diligence.
FOR IMMEDIATE RELEASE
PRLog (Press Release) – Aug 31, 2009 – Since the advent of coronary stents, followed by the emergence of drug eluting stents, the field of stents in the treatment of coronary artery disease has been characterized by aggressive development of new technologies, from minor changes in strut design and drug-coating processes to more radical thinking of the kind that lead from bare metal stents to drug-eluting stents. The coronary stent market is currently in a phase in which the clinical and market success of drug-eluting stents introduced six years ago has stimulated innovation toward emergence of new drug-eluting stent types from many competitors. While the less invasiveness of coronary stents (delivered percutaneously) and outcomes of drug-eluting stents that are nearly comparable to coronary bypass are enabling coronary stents to expand the absolute market of coronary stents by capturing caseload from CABG, the market once dominated by Johnson & Johnson’s Cordis division is now becoming progressively fragmented with new competitors. The market is now facing new challenges with the pending emergence of bioabsorbable stents, drug-eluting balloons and other competitive alternatives to the established stent market.
The global market for coronary stents, examining the products, technologies, companies and worldwide markets for bare metal, drug-eluting and other coronary stents, is the subject of MedMarket Diligence’s report #C245, "Worldwide Coronary Stents 2008-2017" (published May 2009). See http://mediligence.com/rpt/rpt-c245.htm.
"The nature of coronary artery disease, as a major source of morbidity and mortality worldwide, and the support (including especially reimbursement) that treatments receive in the healthcare arena, is a major impetus for technology development," says Patrick Driscoll of MedMarket Diligence. According to Driscoll, there are no fewer than 75 active companies developing and marketing coronary stents and competitive technologies, and the market is likely to become even more consolidated unless new, innovative anti-restenosis technologies are introduced that demonstrate profound clinical advantages over existing options.
The market is facing the emergence, in particular, of bioabsorbable stents, which have demonstrated their potential to provide the necessary anti-restenotic benefit following percutaneous intervention (e.g., angioplasty), then "simply" dissolve and be absorbed at six months or later. Such a device has the potential to eliminate longer term biocompatibility and otherwise inflammatory risk associated with permanently implanted stents. Bioabsorbable stents, too, may be bare or, more likely, contain drug coatings.
The MedMarket Diligence report details the worldwide market for the use of alternative stent devices (cardiac stents or heart stents) in the treatment of coronary artery disease. The report assesses the treatment of coronary artery disease by alternative treatment methodologies (percutaneous intervention with or without stenting, coronary artery bypass grafting alternatives and other medical/surgical treatment options), with estimated current/forecast caseload across treatment types.
The report details currently approved coronary stents, providing data on current and forecast impact on the market. The report also details the current state of product development in bare stents, drug-coated or drug-eluting stents and bioabsorbable stents in coronary applications and details the products under development, the anticipated timeline and impact of their market introduction. The report assesses the current and ten-year forecast global market for coronary stents, with segmentation by U.S., Europe, Asia/Pacific and Rest of World. The report provides competitor market shares by these geographic regions. The leading and key emerging coronary stent manufacturers are profiled with current product offerings, development status and market strengths/advantages.
Treatment of acute coronary artery disease was first accomplished surgically via the coronary artery bypass graft procedure some 45 years ago, then by angioplasty 32 years ago and finally by stenting 23 years ago. Despite the evolution of treatment alternatives (which continue to evolve), CABG has represented a benchmark, if not gold standard, against which alternative treatments are judged. Below is an excerpt from the MedMarket Diligence report, "Worldwide Market for Drug-Eluting, Bare Metal and Other Coronary Stents, 2008-2017" (Report #C245).
Coronary artery bypass graft (CABG) surgery is one of the therapies that can be used to treat patients whose coronary arteries are excessively blocked. CABG patients are typically selected for the procedure depending on the extent of their disease and the severity of symptoms while taking into account the patient’s age and the presence of other medical conditions that might make a CABG procedure too risky.
The goal of CABG surgery is to relieve symptoms of coronary artery disease, including angina, to allow the patient to return to a normal lifestyle and to lower his or her risk of suffering a heart attack or other cardiac incident.
Roughly 1,313,000 inpatient PCI procedures were performed in 2006 while 448,000 inpatient bypass procedures were performed, according to the American Heart Association. More than 800,000 CABG procedures were performed worldwide annually.
An open CABG procedure uses a blood vessel graft to restore normal blood flow to the heart. Most often, three or four arteries are bypassed in a single surgery. Typically, the grafts are harvested from the patient’s own arteries and veins from the chest (thoracic), leg (saphenous) or arm (radial). Internal mammary arteries (IMAs, also known as internal thoracic arteries [ITAs]) are the most common types of grafts used because of the excellent long-term success rates associated with use of these arteries. Often, ITAs can remain intact at their origin and thus maintain their own oxygen-rich blood supply. The other end is sewn to the coronary artery below the site of the blockage. Upwards of 90% of all CABG patients receive at least one internal artery graft. Other thoracic arteries used in CABG include the gastroepiploic and the inferior epigastric arteries.
To perform an open CABG procedure, the patient is placed on a cardiopulmonary bypass (CPB or heart-lung bypass) machine that temporarily takes over the function of the heart and lungs during surgery, thus maintaining the circulation of the blood and the oxygen content of the body. This “on-pump” surgery allows the surgeon to perform the bypass on a still heart.
Unfortunately, complications associated with CPB machines can be significant. These can include: postperfusion syndrome, hemolysis, capillary leak syndrome, clotting of blood in the circuit (particularly in the oxygenator), stroke, air embolism, device leakage (the patient will lose blood perfusion of tissues if a line is disconnected), kidney problems, and problems with mental clarity and memory.
Also, the costs incurred for procedures using a CPB machine are typically very significant. As such, several alternative procedures have been developed that allow coronary artery bypass to be achieved without the use of a CPB or heart-lung machine.
With a traditional, open CABG, patients typically remain in the intensive care unit for one to two days after the surgery, then are transferred to a standard nursing unit for another three to five days. Generally speaking, an average hospital stay for conventional CABG patients is 6–10 days. Full recovery usually occurs within two or three months.
Some results still point to the superiority of CABG over DES in some patient groups, such as those with multivessel disease. For instance, results published online April 6, 2009 (ahead of print in Circulation) showed that in nearly 4,000 patients with multivessel coronary artery disease, the longer-term rates of myocardial infarction, death, and TVR after stenting was significantly higher with DES. The rates in this study, led by Shengshou Hu, Md, PhD of Fuwai Hospital (Beijing, China), were higher than those found in the DES arms of Syntax. For this study, 1,834 patients had DES while 1,886 had CABG between April 1,2004 and December 21, 2005. After three years of follow-up, the DES patients showed unadjusted TVR rate to be 17.6% versus 4.2% in CABG patients. However, because the study was nonrandomized, many physicians are reluctant to put much stock in the findings. Also, the DES used in the study were not commercial stents from the United States but instead were developed by Chinese companies. Both paclitaxel and sirolimus stents were used in the study.
Techniques for the performance of CABG continue to evolve, spanning off-pump ("beating heart") bypass, minimally invasive options (e.g., minimally invasive direct coronary artery bypass graft or MIDCAB), and even percutaneous CABG.