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.

Wound healing factors; Growth in peripheral stenting; Nanomed applications

From our weekly email to blog subscribers…

Extrinsic Factors Affecting Wound Healing

From Report #S251, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.”

Extrinsic factors affecting wound healing include:

Mechanical stress
Desiccation and maceration
Chemical stress
Other factors

Mechanical stress factors include pressure, shear, and friction. Pressure can result from immobility, such as experienced by a bed- or chair-bound patient, or local pressures generated by a cast or poorly fitting shoe on a diabetic foot. When pressure is applied to an area for sufficient time and duration, blood flow to the area is compromised and healing cannot take place. Shear forces may occlude blood vessels, and disrupt or damage granulation tissue. Friction wears away newly formed epithelium or granulation tissue and may return the wound to the inflammatory phase.

Debris, such as necrotic tissue or foreign material, must be removed from the wound site in order to allow the wound to progress from the inflammatory stage to the proliferative stage of healing. Necrotic debris includes eschar and slough. The removal of necrotic tissue is called debridement and may be accomplished by mechanical, chemical, autolytic, or surgical means. Foreign material may include sutures, dressing residues, fibers shed by dressings, and foreign material which were introduced during the wounding process, such as dirt or glass.

Temperature controls the rate of chemical and enzymatic processes occurring within the wound and the metabolism of cells and tissue engaged in the repair process. Frequent dressing changes or wound cleansing with room temperature solutions may reduce wound temperature, often requiring several hours for recovery to physiological levels. Thus, wound dressings that promote a “cooling” effect, while they may help to decrease pain, may not support wound repair.

Desiccation of the wound surface removes the physiological fluids that support wound healing activity. Dry wounds are more painful, itchy, and produce scab material in an attempt to reduce fluid loss. Cell proliferation, leukocyte activity, wound contraction, and revascularization are all reduced in a dry environment. Epithelialization is drastically slowed in the presence of scab tissue that forces epithelial cells to burrow rather than freely migrate over granulation tissue. Advanced wound dressings provide protection against desiccation.

Maceration resulting from prolonged exposure to moisture may occur from incontinence, sweat accumulation, or excess exudates. Maceration can lead to enlargement of the wound, increased susceptibility to mechanical forces, and infection. Advanced wound products are designed to remove sources of moisture, manage wound exudates, and protect skin at the edges of the wound from exposure to exudates, incontinence, or perspiration.

Infection at the wound site will ensure that the healing process remains in the inflammatory phase. Pathogenic microbes in the wound compete with macrophages and fibroblasts for limited resources and may cause further necrosis in the wound bed. Serious wound infection can lead to sepsis and death. While all ulcers are considered contaminated, the diagnosis of infection is made when the wound culture demonstrates bacterial counts in excess of 105 microorganisms per gram of tissue. The clinical signs of wound infection are erythema, heat, local swelling, and pain.

Chemical stress is often applied to the wound through the use of antiseptics and cleansing agents. Routine, prolonged use of iodine, peroxide, chlorhexidine, alcohol, and acetic acid has been shown to damage cells and tissue involved in wound repair. Their use is now primarily limited to those wounds and circumstances when infection risk is high. The use of such products is rapidly discontinued in favor of using less cytotoxic agents, such as saline and nonionic surfactants.

Medication may have significant effects on the phases of wound healing. Anti-inflammatory drugs such as steroids and non-steroidal anti-inflammatory drugs may reduce the inflammatory response necessary to prepare the wound bed for granulation. Chemotherapeutic agents affect the function of normal cells as well as their target tumor tissue; their effects include reduction in the inflammatory response, suppression of protein synthesis, and inhibition of cell reproduction. Immunosuppressive drugs reduce WBC counts, reducing inflammatory activities and increasing the risk of wound infection.

Other extrinsic factors that may affect wound healing include alcohol abuse, smoking, and radiation therapy. Alcohol abuse and smoking interfere with body’s defense system, and side effects from radiation treatments include specific disruptions to the immune system, including suppression of leukocyte production that increases the risk of infection in ulcers. Radiation for treatment of cancer causes secondary complications to the skin and underlying tissue. Early signs of radiation side effects include acute inflammation, exudation, and scabbing. Later signs, which may appear four to six months after radiation, include woody, fibrous, and edematous skin. Advanced radiated skin appearances can include avascular tissue and ulcerations in the circumscribed area of the original radiation. The radiated wound may not become evident until as long as 10-20 years after the end of therapy.

Source: “Wound Management to 2024”, Report #S251.

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Source: “Global Market Opportunities in Peripheral Arterial and Venous Stents, Forecast to 2020”, Report #V201.

Selected Therapeutic and Diagnostic Applications of Nanotechnology in Medicine

Below are selected applications for neuromedical technologies in development or on the market currently.

Drug Delivery
Chemotherapy drug delivery
Magnetic nanoparticles attached to cancer cells
Nanoparticles carrying drugs to arterial wall plaques
Therapeutic magnetic carriers (TMMC) [guided using magnetic resonance navigation, or MRN]

Drugs and Therapies
Combatting antimicrobial resistance
Alzheimer’s Disease
Infectious Disease

Tissue, cell and genetic engineering involving nanomedical tools
Nanomedical tools in gene therapy for inherited diseases
Artificial kidney
ACL replacements
Implanted nanodevices for alleviation of pain


Nanomedicine and Personalized Treatments

Source: Report #T650, “Global Nanomedical Technologies, Markets and Opportunities, 2016-2021”. Report #T650.

Drug-Eluting Stents’ New Growth and Opportunities: Any Doubts?

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See the December 2015 report, “Global Market Opportunities in Peripheral Arterial and Venous Stents, Forecast 2020”. A $500 advance discount is available until publication.
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The worldwide market for drug-eluting, as well as bare, bioresorbable and other stents, is now the subject of the May 2009 report by MedMarket Diligence, Report #C245.

Below is an excerpt from MedMarket Diligence’s coverage of  the drug-eluting stents market in mid-2008.  The previous scarcity of long term data left some uncertainty about DES’ clinical and market potential, compared to bare stents or even coronary artery bypass grafting, but the completion of multiple clinical trials has gone a long way toward ensuring at least several years of solid growth and the proliferation of competitors in the DES market.

After clinical trial results were released in 2006 showing that bare metal stents had outperformed drug-eluting stents (DESs), the market for DESs took what turned out to be fairly minor hit, with some physicians backing away from the newer technology and choosing to implant bare metal stents instead. Subsequent to those results, a number of studies revealed that DES offer better outcomes with morbidity that is competitive with bare metal stents (see the clinical trials list here).

Four-year data presented in September 2007 at the European Society of Cardiology meeting showed that in a 35,000-patient Swedish registry, patients receiving DESs are not at a higher risk of dying or suffering a heart attack as compared to patients receiving bare metal stents. While DESs do present a small increased risk of late-stent thrombosis after the first year, this is offset by better outcomes in the early months after implantation.

Nonetheless, it remains that stent sales have decreased across the board over the last two years and many physicians still need to be convinced of the devices’ performance and safety. In addition, opportunity is still great for those who would develop new DES technology that can further decrease the rate of restenosis.

The fourth quarter of 2007 proved to be the worst yet for the DES market. While some studies showed that DESs comprised nearly 90% of all stents implanted in 2006, that figure fell to roughly 60% by the end of 2007. These declines—fueled by restenosis concerns as well as studies showing that in some patients, stenting should be delayed in favor of drug therapy—led to layoffs at Boston Scientific and Johnson & Johnson. Now that the market has leveled off, the percentage of DES stents implanted seems to be holding at roughly 60%.

Meanwhile, the FDA proposed in March 2008 more stringent guidelines for DES clinical trials. Under the new guidelines companies must submit clinical trial data on patients at one and two years post-op, as compared to the previously required nine-month period. In addition, companies should continue to monitor patients for five years post-op. While this does not affect stents currently in the market (namely Cypher by Johnson & JohnsonCordis, Taxus Liberte by Boston Scientific, and Endeavor by Medtronic), it does result in a significant delay for companies bringing their first DES to market.

Johnson & Johnson

Johnson & Johnson was the first company to bring a DES to market through its Cordis subsidiary. However, Cordis saw a 15% operational sales decline in the first quarter of 2008 as compared to the prior year, primarily due to increased competition as well as contraction of the DES market worldwide.

In December 2007, Johnson & Johnson unveiled a new ad campaign designed to reassure consumers as to the safety of its Cypher stent as well as combat the competition in the market for DES. The company also set up a web site ( to provide marketing and general product information to patients and physicians. The direct-to-consumer marketing approach has been criticized by many as an effort by the company to minimize physician input as to which procedures would be appropriate for which patients.

In May 2007, Johnson & Johnson announced it would discontinue marketing its CoStar stent outside the United States, would no longer seek U.S. FDA approval of the device, and had ceased ongoing clinical trials for the stent. The CoStar stent was developed by Conor Medsystems, a company Johnson & Johnson had purchased a few months earlier. The decision was made after the CoStar failed to meet its primary goal in the COSTAR II study. In the COSTAR II study, the stent was compared to Boston Scientific’s Taxus Express2 (also a paclitaxel-coated stent). While the CoStar did not present safety issues, neither did it prove superiority to the Taxus stent. Researchers said the CoStar stent presented ineffective dosing of paclitaxel, resulting in more frequent repeat revascularization procedures. The company is now working to develop a new version of the CoStar that uses sirolimus, the drug used on the Cypher stent. In a market where physicians have been reverting back to implanting bare metal stents due to performance issues of DESs, product manufacturers are looking for devices that will not only match the performance of but will outperform currently available DESs.

In other disappointing news, Conor’s GENESIS study involving a pimecrolimus-eluting Corio stent was terminated in late March 2008. The study involved three devices: the company’s Corio stent; its dual-drug (pimecrolimus and paclitaxel) SymBio stent; and its paclitaxel CoStar stent. After six months follow-up, in-stent late loss was greatest with the Corio stent, mid-range with the SymBio stent and least with the CoStar stent.

A new randomized clinical trial dubbed the RES-ELUTION study began in March 2008 to compare a Conor coronary stent that elutes sirolimus to Boston Scientific’s Taxus Liberte paclitaxel-eluting coronary stent. The primary endpoint of the study is angiographic in-stent late lumen loss at six months. Secondary endpoints include target lesion failure, target vessel failure, major adverse cardiac events (MACE), stent thrombosis, target lesion revascularization, target vessel revascularization, and angiographic in-stent and in-segment binary restenosis at six months. The multicenter study will be conducted at 40 sites outside the United States and resulting data will be used to support a CE Mark filing.

Boston Scientific

Among the sets of clinical data released over the past several months, Boston Scientific announced positive data from the ARRIVE registries and the TAXUS studies. In addition, Boston Scientific announced in February 2008 the start of the PROENCY registry, which will assess different Olimus-eluting stents, including its Promus/Xience V (everolimus), Medtronic’s Endeavor (zotarolimus) and Johnson & Johnson’s Cypher (sirolimus) stents. The registry will enroll up to 2,500 patients with simple and complex lesions at multiple sites in several European countries. Half of the patients will receive the Promus stent and half will receive either the Cypher or the Endeavor stent to attain a 2:1:1 ratio. The primary endpoint will be the rates of MACE (cardiac death, all myocardial infarction and target vessel revascularization) at 12 months.

Also in February 2008, a U.S. District Court in Texas reached a verdict finding that Boston Scientific’s Taxus Express and Taxus Liberte DESs infringe on a patent held by Dr. Bruce Saffran. While the jury awarded damages of $431 million, Boston Scientific plans to contest the verdict.

In May 2008, a World Intellectual Property Organization arbitration panel decided in favor of Boston Scientific, refuting a claim by Medinol alleging the Liberte and Taxus Liberte stents infringed various U.S. and European patents held by Medinol. Under the terms of the settlement agreement, Medinol holds the right to appeal to another WIPO panel.


In February 2008, Medtronic received FDA approval for its Endeavor zotarolimus-eluting coronary stent, becoming the third company to receive marketing approval for a DES in the United States.

In May 2008, Medtronic saw the first implants of its next-generation Endeavor Resolute stent as part of the RESOLUTE III trial comparing Medtronic’s stent to Abbott’s Xience V. The pivotal RESOLUTE III trial will be conducted in more than 100 countries outside the United States. The Endeavor Resolute stent received CE Mark approval in October 2007 and is still limited to investigational use in the United States.

The Endeavor Resolute incorporates the company’s biocompatible polymer dubbed BioLinx, designed to offer the same biocompatibility as the Endeavor’s phosphorylcholine (PC) while lengthening the amount of time the drug is exposed in the vessel. BioLinx blends hydrophilic and hydrophobic elements and is the first polymer created specifically for a DES.

Abbott Vascular

Results from clinical studies performed with Abbott Vascular’s Xience stent have been encouraging and the company expects to receive FDA approval for the device in 2008. Xience received CE Mark approval in 2006.

Over the last few months, data from the SPIRIT II and III trials have been released by the company. In May 2008, the first long-term data from the pivotal SPIRIT III trial was presented at the EuroPCR 2008 meeting showing the Xience V everolimus-eluting coronary stent performed well against Boston Scientific’s Taxus stent. At two years follow-up, the Abbott stent showed a 45% reduction in the risk of MACE (7.3% for Xience V versus 12.8% for Taxus) and a 32% reduction in the risk of target vessel failure (10.7% for Xience V versus 15.4% for Taxus). The prospective, randomized SPIRIT III trial involves 1,002 patients at several sites in the United States.

Abbott Vascular is also working on a drug-eluting, fully bioabsorbable vascular stent (BVS). The device is currently the focus of the ABSORB clinical trial, for which positive one-year results were published in The Lancet (371[9616]: 899–907, March 15, 2008), The results showed 100% procedural success in 30 patients and 94% device success (29 of 31 implantation attempts). At one year, the MACE rate was 3.3% and no late stent thromboses were recorded. The prospective, nonrandomized ABSORB trial is designed to accommodate up to 60 patients in Belgium, Denmark, France, New Zealand, Poland and The Netherlands.

Biosensors International

In April 2008, Biosensors International launched its BioMatrix drug-eluting stent outside the United States. The device combines a biodegradable polymer with the company’s proprietary drug Biolimus A9. The BioMatrix stent received CE Mark approval in January 2008.

Simultaneously with the product launch, Biosensors began enrollment in a five-year patient registry designed to track the safety and efficacy of the BioMatrix stent in up to 5,000 patients.

In March 2008, Biosensors opened enrollment in the BEACON II registry, which is designed to enroll 1,000 patients in 15 centers across Asia, Australia and New Zealand. Results from the original BEACON study were presented in October at the TCT 2007 meeting. In that study, the BioMatrix showed a 2.1% target vessel revascularization rate and an 86.5% MACE rate.

Biosensors International is also striving to make its presence known in the DES market through corporate liaisons. For instance, in Europe, Terumo markets the company’s BioMatrix under the Nobori label.

In another agreement, Biosensors acquired the remaining 50% equity of JW Medical Systems in May 2008. JW Medical Systems was established in 2003 as a 50:50 equity joint venture between Biosensors and Shandong Weigao Group in China. JW Medical Systems, which will now likely be absorbed into Biosensors, has been developing the Excel sirolimus-eluting stent. The CREATE registry study is ongoing in China and incorporates the Excel biodegradable polymer DES. Results presented in October at the TCT 2007 meeting showed the stent had achieved both primary and secondary endpoints with a MACE rate of 0.63% and 1.4%, respectively, in 30-day and 6-month follow-ups. Excel has been available commercially in China since December 2005.


Xtent is developing its Custom NX DES, which incorporates Biolimus A9 licensed from Biosensors International. In December 2007, Xtent submitted its application for CE Mark registration, based on the CUSTOM I, II, and III trials. In March 2008, the company was informed that it would receive a response to its CE Mark application in the second quarter of 2008. Xtent had previously filed an IDE application with the FDA in September 2007 to gain the right to begin U.S. trials.


French company Stentys is developing a bifurcated coronary DES, which was first implanted into a human patient in September 2007. The successful procedure involved a 56-year-old male patient in Siegburg, Germany. The Stentys device is unique in that the stent-opening for the side branch can be created anywhere in the stent after implantation, thus ensuring that the procedure’s success is not dependent on accurate positioning.

In March 2008, Stentys announced that it had completed an $18 million Series B round of venture financing, led by the U.K.-based Scottish Equity Partners. The financing will be used to complete clinical trials and obtain CE Mark status.

MIV Therapeutics

MIV Therapeutics (MIVT) saw the first human implantation of its hydroxyapatite-coated VESTAsync DES and the launch of the MIVT Pilot Trial in May 2007. The trial will evaluate the safety and efficacy of MIVT’s polymer-free nanoscale microporous hydroxyapatite DES for the treatment of single de novo lesions in native coronary arteries. Dr. Alexandre Abizaid performed the procedure at the Institute Dante Pazzanese of Cardiology in Sao Paulo, Brazil. The MIVT stent is based on the company’s GenX coronary stent system and incorporates a coating that is only 700 nanometers thin.

In October 2007, Dr. Abizaid performed a live four-month follow-up case at the TCT 2007 conference. The physician also implanted a VESTAsync stent into another patient as part of the same live presentation. Follow-up data on the first 13 patients in the trial showed average late-lumen loss of 0.27 mm in-stent and 0.18 mm in-lesion with 0% restenosis. IVUS analysis showed volumetric obstruction of 2.8% and all patients were thrombosis-free.

Data presented in November 2007 at American Heart Association meeting showed that in animal studies, MIVT’s VESTAsync hydroxyapatite coronary stent coating with low-dose sirolimus resulted in less fibrinoid than seen with Johnson & Johnson’s Cypher stent. The data also showed a statistically significant difference between an increase in sirolimus and an increase in fibrinoid material, a strong indicator of delayed healing. Even though the MIVT stent presented a four-fold lower dosage of sirolimus as compared to the Cypher stent, less fibrinoid was seen overall.

Nine-month VESTAsync data presented at the American College of Cardiology meeting in March 2008 was consistent with the data presented at the October 2007 TCT meeting, with no significant difference between the four- and nine-month results. In addition, no late-acquired incomplete stent apposition, stent thrombosis or MACE were reported. The company is now gearing up for a larger clinical trial accommodating approximately 100 patients.

Other DES Developments

In May 2007, Brookwood Pharmaceuticals and Targeted Technology Ventures collaborated to create a joint venture—Aeon Bioscience—to develop a new DES that would be more resistant to restenosis. Aeon Bioscience is working to develop a new polymer coating with better biocompatibility than seen with the current market leaders. In October 2007, Brookwood Pharmaceuticals was acquired by SurModics, a development that is not expected to hinder Aeon Bioscience in its product development efforts.

In October 2007, ARIAD Pharmaceuticals signed a licensing agreement with ICON Medical to develop and commercialize DES devices that incorporate ARIAD’s mTOR inhibitor, deforolimus. Under the agreement, ARIAD receives an equity stake in ICON, up to $27 million in payments based on achievement of certain clinical, regulatory and commercial milestones for two products and royalties on worldwide sales of all ICON medical devices delivering deforolimus. ICON will build the DES around its proprietary metal alloy, Nuloy.

In December 2007, Devax completed patient enrollment in its DIVERGE clinical trial evaluating its Axxess bifurcated DES. To date, 302 patients are enrolled in the prospective, multicenter trial. The Devax Axxess Biolimus A9–eluting DES is a self-expanding nitinol stent designed for treating coronary and vascular bifurcation lesions.

In June 2007, Biotronik completed enrollment in its ProLimus I study, a prospective, nonrandomized trial incorporating 61 patients at five centers in Belgium and Germany and using the company’s pimecrolimus-eluting ProGenic stent.

CardioMind began its first-in-man trial in March 2008 with its Sparrow DES, a device that is 70% smaller in diameter than other DES on the market. The CARE II clinical trial began at St. Vincent’s Hospital in Melbourne, Australia, and will eventually enroll 220 patients. The Sparrow stent incorporates the SynBiosys biodegradable polymer stent from SurModics, which will allow the stent to gradually return to a bare metal state.

Endovasc and TissueGen mutually agreed in May 2007 to dissolve their joint venture exploring development of biodegradable stents for cardiovascular, ureteral and prostate applications. All intellectual property has returned to the respective owners.

Medlogics is developing its Synergy Biomatrix non-polymeric coating, which can be applied to stainless steel, nickel titanium and cobalt chromium alloys. The Synergy Biomatrix surface is less than 2 microns thick, as compared to polymeric coatings that are typically between 7.5 and 10 microns. The coating is also biodegradable and returns the stent to bare metal after releasing the drug. Current development programs are focusing on the Cobra-P (paclitaxel) and Cobra-Q (undisclosed drug) DESs. Medlogics has received a CE Mark for its bare Cobra stent and is launching the device in Europe in 2008. In February 2008, Medlogics signed an agreement granting the company licensing rights to CV Therapeutics’ biopolymer stent coating.

Below is a sampling of active drug-eluting stent companies:

Abbott Vascular (Redwood, City, CA;
Aeon Bioscience (Birmingham, AL; [under construction])
Avantec Vascular (Sunnyvale, CA; [under construction])
B. Braun Melsungen (Melsungen, Germany;
Lepu Medical (Beijing, China;
Bioabsorbable Therapeutics, Inc. (BTI; Menlo Park, CA;
Biosensors International (Newport Beach, CA; Singapore;
Biotronik (Lake Oswego, OR; Berlin, Germany;
Blue Medical Devices (Helmond, The Netherlands;
Boston Scientific (Natick, MA;
CardioMind (Sunnyvale, CA;
Conor Medsystems (Menlo Park, CA;
Cook Medical (Bloomington, IN;
Cordis (New Brunswick, NJ;
CorNova (Burlington, MA;
Devax (Irvine, CA;
DISA Vascular (Cape Town, South Africa;
Endovasc (Montgomery, TX;
Estracure (Montreal, Quebec, Canada;
ICON Medical (Cleveland, OH; [under construction])
Johnson & Johnson (J&J; New Brunswick, NJ;
JW Medical Systems (See Biosensors International)
Kaneka (Osaka, Japan;
Medinol (Jerusalem, Isreal;
Medlogics Device Corporation (MDC; Santa Rosa, CA: [under construction])
Medtronic Vascular (Minneapolis, MN;
MicroPort Medical (Shanghai, China;
MIV Therapeutics (MIVT; Vancouver, BC, Canada;
OrbusNeich (Wanchai, Hong Kong;
Relisys Medical Devices (Hyderabad, India; [under construction])
Sahajanand Medical Technologies (SMT; Surat, India;
Sorin (Saluggia, Italy;
Stentys (Clichy, France;
Terumo (Shibuya-ku, Japan;
TissueGen (Dallas, TX;
Translumina (Hechingen; Germany;
Vascular Concepts (Barcelona, Spain;
X-Cell Medical (Monmouth Junction, NJ;
Xtent (Menlo Park, CA;

The worldwide market for drug-eluting, as well as bare, bioresorbable and other stents, is now the subject of the May 2009 report by MedMarket Diligence, Report #C245.

Drug-Eluting Balloon Catheters

[Through the course of researching and analyzing coronary artery disease treatments, technologies and markets for our May 2009 worldwide coronary stents market report, we have compiled data on the ancillary market of drug-eluting balloons, which we synopsize below.]

Drug-Eluting Balloons

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

The concept behind the technology is based on the assumption that delivering a rapid release of drugs into the arterial tissue is more effective than the gradual release of drugs, as seen with drug-eluting stents. Another side benefit of the technology would be significant cost-savings. Angioplasty balloons currently used typically cost roughly $400 each.


Technologies/approaches being developed by specific companies include:

  • drug-coated angioplasty catheters for coronary and peripheral applications
  • development of paclitaxel-coated angioplasty catheter
  • coating standard angioplasty balloons with paclitaxel
  • bioabsorbable coating on balloon drug-eluting balloon catheter
  • mix of paclitaxel and hydrophilic spacer on balloon surface
  • paclitaxel-eluting balloon catheter for in-stent restenosis, bifurcated lesions, small diameter lesions, etc.
  • polymer-based drug delivery on balloon catheter
  • paclitaxel-eluting balloon catheter with controlled drug release for coronary and peripheral applications
  • drug-eluting balloon catheter with surface that penetrates, splits stenosis to facilitate drug delivery


 Developers of Paclitaxel-Eluting Balloon Catheters

See report #C245 for table of companies with products in development

Source:  MedMarket Diligence report #C245, "Worldwide Market for Drug-Eluting, Bare and Other Coronary Stents, 2008-2017." May 2009. 

Purchase for download:  Report #C245, "Worldwide Coronary Stents 2009, PDF" — $2,850.00
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Medtech startup formations economically immune?

There is certainly the possibility (despite my doubts) that the current economic slowdown in global markets will have major effects on the medical technology industry. One simply cannot deny that there is simply less VC or other cash floating around that might be put to medtech investment. And maybe, as has occurred in the past (e.g., in the post dotcom bubble era), investment that does take place will move further downstream, away from the speculative risk of very early startups. In hindsight, it is easy to see such trends and developments.

But looking forward, it is difficult to see significantly diminished demand for the promise of medical technology development. Companies continue to be founded at a strikingly active pace.

The Medtech Startups Database, from MedMarket Diligence, has over the past half dozen years accumulated the data on nearly 900 new medtech companies under two years old — a remarkable pace of entrepreneurship.  In the very recent activity in company formation, here are a samping of the technologies these companies are pursuing:

  • Laser devices to “weld” biological tissues together for wound closures.
  • Drug-coated urinary and other catheters and stents that are designed to prevent or treat scar tissue.
  • Artificial heart technologies.
  • Heart pumps.
  • Compliant balloon technologies.
  • Device for mitral valve repair without need for sternotomy.
  • Pharmaceutical treatments for ischemia and vascular disease, focused on peripheral artery disease.
  • Non-polymeric drug eluting stent
  • Device technology in diabetes management.
  • Medical device inflatables, including devices for biological navigation such as in support of colonoscopy and other endoscopy.
  • Minimally-invasive products for motion-preserving spine surgery.
  • Minimally invasive treatment of vertebral compression fractures.
  • Minimally invasive treatments for removing varicose veins.
  • Drug-coated angioplasty for coronary and peripheral applications


Medtech Startups Database described here. See pending and recent MedMarket Diligence reports: Sealants, Glues Wound Closure (coming in December), Ablation Technologies,  and Spine Surgery.