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)

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.

Percutaneous Transluminal Angioplasty and Stenting Reconsidered

Originally developed by the Swiss physician Andreas Gruentzig as a less traumatic alternative to CABG, and first performed in the U.S. in 1978, percutaneous transluminal coronary angioplasty (PTCA) has soon emerged as a mainstream revascularization modality, particularly well-suited for singular concentric coronary artery occlusions.

PTCA is a minimally invasive procedure intended to restore normal (or nearly normal) blood circulation in occluded coronary arteries through a radial dilation of atherosclerotic plaque and its compression against arterial wall with transluminally-placed inflatable balloon.

In PTCA procedure, occluding coronary lesion is first crossed with appropriate guidewire, which is typically inserted under fluoroscopic guidance through a puncture in femoral artery and brought to the treatment site via iliac artery and aortic tree. A special balloon-tipped catheter is then deployed over the guidewire across the targeted lesion and repeatedly inflated to provide a required reopening of the arterial lumen. The catheter is then withdrawn and arterial puncture is secured with the use of external pressure aids or special vascular puncture closure device.

Despite some indisputable benefits of “plain old balloon angioplasty,” its ultimate clinical efficacy was seriously compromised by the disappointingly high rate of restenosis that ran as high as 50% at six months and typically required re-intervention. Introduction of coronary bare metal stents (BMS) in the early 1990s allowed to partially alleviate that problem by reducing the average restenosis rate by about one-half. Stents also helped to virtually eliminate many of the complications of conventional angioplasty, such as abrupt and unpredictable collapse and closure of the vessel, which resulted in emergency bypass surgery.

Since the introduction of bare metal coronary stents, the usage of angioplasty expanded considerably, supplanting CABG as the most commonly employed modality of myocardial revascularization.

By the beginning of the past decade, though, growth in PTCA and coronary stenting caseloads started to slow down in the U.S., Europe, and Japan reflecting significant penetration of technically feasible CAD indications and a disappointingly high rate of post-PTCA and in-stent restenosis. The problem of restenosis represented a single major handicap of coronary angioplasty/stenting, which hampered its ultimate clinical outcomes and often forced a revision and eventual conversion to bypass surgery.

In the opinion of many leading clinicians and industry’s analysts, introduction of drug-eluting stents (DES) represented the single most important innovation in endovascular therapy, since the advent of stenting and angioplasty that was bound to have a revolutionary impact on interventional cardiology practices.  In addition to effectively remedying the nagging problem of coronary restenosis (by reducing its rates to mid-low digit figures), the drug-eluting devices also enabled interventional cardiologists to successfully manage coronary indications and patient caseloads that were traditionally deemed unsuited for angioplasty and stenting. The latter include treatment of small diameter vessels, long and bifurcated lesions, left main artery and multivessel disease, as well as expanded coverage of high-risk patient cohorts with advanced diabetes, renal insufficiency/failure and recent major AMI.

Unfortunately, in the middle of the past decade, one could witness a gradually growing concerns about relatively high incidence (compared to BMS) of late and very late stent thrombosis (often leading to AMI and death) and overall safety of DES, that have prompted several warning letters, but were generally ignored due to initial exuberance about superb antirestenotic performance of DES technology. Following a release of disturbing findings from several major studies in 2006, the cited concerns appeared to reach a “critical mass” bringing the safety issues to the forefront of renewed DES debates and ultimately prompting a very significant decline in DES usage and cumulative PCI procedure volumes in the U.S. and Europe.

In the view of many leading clinicians, the higher propensity of drug-eluting stents to late (and very late) thrombosis is stemming from the very nature of current DES technology which is focused primarily on prophylaxis of binary restenosis via distortion and inhibition of natural healing processes involving neointimal outgrowth. The latter, by definition, lead to a significantly delayed epithelialization and protracted stent struts exposure to the blood stream, which have been identified as the main sources of thrombogenicity. According to multiple IVUS and pathology studies, incomplete endothelialization of DES (with associated bare strut exposure and device malapposition) is commonly observed at 3 to 4 years post-implantation, in contrast to full epithelial coverage of BMS occurring at 5 to 6 months after stent placement.

Early termination of dual (aspirin-clopidogrel) antiplatelet regimens due to patient’s non-compliance, serious complications, or other reasons appears to represent another major contributing factor to onset of late thrombotic events. Based on available data, the vast majority of DES-related thrombosis episodes tend to occur at 1.0 to 3.5 years post-implantation, or after the recommended 12-month period of dual antiplatelet therapy. According to clinical literature, other factors implicated in the occurrence of late and very late DES thrombosis include presence of inflammatory polymer on stent, incomplete drug elution, rate of drug elution, cytotoxicity of chosen drug, as well as poor DES patient selection (e.g., utilization of DES in high-risk diabetics, and their off-label uses in small diameter vessels, patients with long and bifurcated lesions, etc.).

Most of the cited problems were effectively addressed by the next-generation DES devices that combine sophisticated cobalt and platinum alloy stenting platforms and biodegradable drug coatings with super-low-profile delivery and minimally traumatic deployment systems.

It is assumed that clinical efficacy and utility of DES technology would be significantly enhanced with the advent of specialty bifurcation-targeting devices, vascular healing-focused biopharmaceutical coatings, and in increased adoption of fully biodegradable stenting systems.

For forecasts of off-pump CABG, on-pump CABG, primary PCI with stenting, and drug-eluting stent-based PCI procedures (separately for U.S. Western Europe, Asia/Pacific and Rest of World), as well as all major cardiovascular surgical and interventional procedures, see Report #C500, “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022.”

New Global Cardiovascular Procedures Report Reveals Medtech Outlook

MedMarket Diligence has published, “Global Dynamics of Surgical and Interventional Cardiovascular Procedures, 2015-2022.”

See link for report description, sources, table of contents, and list of exhibits. The report may be purchased for download.

The report details the therapeutic procedures that address acute and chronic conditions affecting myocardium and vascular system, with relevant prevalences, incidence rates, separate procedure counts for surgical versus interventional and other key splits of the procedure volume.

Screen Shot 2016-08-12 at 9.48.46 AMThe report offers current assessment and projected procedural dynamics (2015 to 2022) for primary market geographies (e.g., United States, Largest Western European Countries, and Major Asian States) as well as the rest-of-the-world.

Each set of forecasts is accompanied by discussion per condition of the changing clinical practice and technology adoption rates, procedural limitations or drivers competitively, the surgical-interventional balance, and the resulting market outlook for cardio manufacturers.

Excerpts available on request.