CDU Contributing Editor

NEW ORLEANS – The market for devices used in interventional radiology is one of the most diverse within the medical technology industry. Interventional radiology addresses a wide range of diseases, many of which typically afflict the expanding elderly population, creating a strong underlying demand that is expected to grow rapidly over the next decade. The 30th annual scientific meeting of the Society of Interventional Radiology (SIR; Fairfax, Virginia), held here in early April, provided a forum for presentation of a wide range of modalities from suppliers in the interventional radiology market.

One of the most pressing unmet needs in interventional radiology is new technologies for the treatment of and, ultimately, for the prevention of stroke. Advances in preventive therapy are now beginning to appear in the form of carotid stents that provide a minimally invasive, non-surgical alternative to carotid endarterectomy for treatment of carotid artery stenosis.

For stroke therapy, the only treatment at present is delivery of Genentech’s (South San Francisco, California) tissue plasminogen activator (tPA) from within three hours of onset. But thrombolysis with IV tPA is not always effective: only 26% of patients with type M1 or M2 clots, which comprise a major type of thrombosis observed in stroke patients, are recanalized with tPA therapy. In addition, clinical studies using IV tPA thrombolysis in stroke patients have shown that it requires between three and four hours to achieve recanalization, and when that time interval is added to the typical delay in reaching the hospital and initiating therapy, most patients are beyond the time window in which optimal efficacy is achievable.

Definitive rapid stroke diagnosis difficult

Another issue in stroke therapy is that techniques for definitive rapid diagnosis of stroke are lacking, as are methods to allow identification of brain tissues than can be salvaged following a stroke. While clinical studies indicate that on average initiation of tPA therapy must occur within three hours of stroke onset in order to achieve maximum benefit, there also is considerable evidence that certain patients will benefit from treatment beyond the three-hour window. However, methods to definitively identify those patients are lacking.

Modalities under development for assessment of brain tissue viability following a stroke include PET imaging, to assess oxygen consumption in compromised tissues; MR diffusion imaging; and assessment of cerebral blood flow, cerebral blood volume, and other hemodynamic parameters using CT imaging. Due to the problems with existing techniques for stroke diagnosis and treatment, only about 10% of stroke patients receive thrombolytic therapy even in the most advanced medical institutions, and overall the percentage is considerably lower, at around 2% by some estimates.

As discussed by Ajay Wakhloo, MD, professor of radiology, neurological surgery and biomedical engineering, and director of the section of neuroendovascular surgery and neurointerventional radiology at the University of Miami School of Medicine (Miami), at the SIR conference, the lack of more effective stroke therapies is not due to a lack of research and development activity in the field. More than 65 intracranial devices have been evaluated in various stroke trials, according to Wakhloo, including clot suction catheters, recanalizing wires, PTA balloon catheters, snares, and clot maceration and emulsification devices.

One promising technology that may improve treatment of thromboembolic stroke is ultrasound-assisted thrombolysis using the MicroLysus Infusion Catheter from EKOS (Bothell, Washington). The device is being evaluated in the Interventional Management of Stroke (IMS) study directed by researchers at the University of Cincinnati and sponsored by the National Institutes of Health (Bethesda, Maryland) and EKOS. The trial was recently expanded from six sites to 12. The MicroLysus catheter combines high-frequency (1 MHz to 2 MHz), low-power (0.45 watt) ultrasound with infusion of a thrombolytic drug to accelerate thrombolysis by mechanically dispersing the drug into a clot and increasing clot permeability. An embedded thermistor in the 2.8 Fr catheter monitors temperature to allow automatic control of the power level and also allows detection of recanalization due to the rapid temperature change that results when blood flow is restored. Initial studies conducted with the device have demonstrated a seven-fold higher rate of recanalization within one hour of starting treatment as compared to rates achieved with intra-arterial tPA infusion alone in separate trials.

Another device for mechanical disruption of clots in stroke patients, the Merci Retriever System, has been developed by Concentric Medical (Mountain View, California). The system uses a microcatheter with a corkscrew-type microwire that is first threaded through the clot. A balloon at the tip is then inflated to stop blood flow, and the wire is retracted into the microcatheter to extract the clot. The device was approved by the FDA in August 2004. In a clinical trial with the Merci catheter, a 48% recanalization rate was achieved, which was increased to approximately 60% when tPA infusion was added.

Another mechanical clot-removal device for use in stroke therapy is being developed by IDEV Technologies (Houston). The IDEV device is a miniaturized thrombectomy catheter with a 4 Fr diameter that will be suitable for use in the cerebral vessels.

Thrombectomy devices a growing focus

In addition, advances in device technology for use in the treatment of deep venous thrombosis (DVT) were described at the SIR conference that promise to improve treatment for the 200,000 to 300,000 patients who develop DVT in the U.S. each year. Thrombectomy devices for use in the larger peripheral vessels, such as in the leg arteries and in dialysis access grafts, also are a focus for R&D investment in the interventional radiology market. As discussed by Suresh Vedantham, MD, of Washington University (St. Louis) at SIR, new devices using pharmacomechanical thrombolysis techniques are proving highly effective for treatment of deep vein thrombosis (DVT). There are 200,000 to 300,000 new cases of DVT annually in the U.S., and 600,000 total cases including recurrences.

The conventional treatment for DVT is catheter-directed thrombolysis, which is effective but requires one to two days, is costly, and is associated with a high risk of bleeding, limiting its utilization. In addition, in about 50% of untreated patients, or in some patients who have residual clot after treatment, post-thrombotic syndrome can occur. Post-thrombotic syndrome affects between 100,000 and 150,000 patients per year in the U.S., and causes significant swelling of the legs as a result of permanent damage to valves in the leg vessels caused by blood clots. In addition to swelling, the resulting impaired circulation in the legs can lead to skin ulcers, affecting 500,000 to 600,000 patients.

Many physicians are not aware of post-thrombotic syndrome, resulting in lack of appropriate therapy in many cases. Pharmacomechanical treatment for DVT promises to reduce the incidence of post-thrombotic syndrome, by providing improved removal of clots, and to increase the percentage of patients who receive appropriate therapy by lowering the cost and reducing the time required for treatment. Devices available for use in DVT therapy include the Helix catheter from ev3 (Plymouth, Minnesota), the AngioJet from Possis Medical (Minneapolis) and the Trellis-8 device from Bacchus Vascular (Santa Clara, California).

The Helix catheter operates at 100,000 rpm to create a vortex that breaks up the clot and is used in combination with a thrombolytic drug in the treatment of DVT. Success rates for clot removal with the Helix are 94% vs. 71% with drug treatment alone, and the treatment time is reduced by 40%. Lower bleeding rates also are achieved. Similar success rates of 93% have been achieved using the Possis AngioJet.

With the Trellis-8 device, success rates for clot removal are 89%, but cost is reduced by more than 60%, treatment time is reduced from two days to as little as 30 minutes, and no bleeding episodes have been reported. The 8 Fr Trellis-8 system includes dual balloons that are inflated on either side of the clot both to prevent embolization of clot fragments and to isolate the thrombolytic drug at the site of the clot, thereby reducing systemic exposure and bleeding risk. A wire is then rotated at 3,000 rpm to mechanically disrupt the clot, en-hancing the enzymatic action of the thrombolytic agent. The Trellis-8 is a new product from Bacchus that is specifically designed for use in DVT treatment, and was cleared by the FDA in February of this year. The device was launched in the U.S. market in April.

Another new device, the Eliminator from IDEV Technologies, was cleared by the FDA in mid-March for use in clearing thrombosed dialysis access grafts and native AV fistulas. Datascope Interventional (Mahwah, New Jersey) also has introduced a new thrombectomy device within the past year, the $595 Prolumen rotational thrombectomy system.

Vascular intervention developments

Devices used in vascular intervention, including peripheral vascular stents and stent-grafts, comprise one of the largest segments of the interventional radiology market, and one of the most rapidly growing segments. The first carotid stent, the Acculink from Guidant Vascular Intervention (Santa Clara, California), which is used in combination with the Accunet embolic protection device, was approved by the FDA in August 2004. Carotid stents address a potential target patient population of 150,000 to 175,000 worldwide who now undergo surgical treatment (carotid endarterectomy) for carotid artery stenosis. Development of the market is being paced by the need to train and accredit physicians to perform the stent procedure, and by delays in setting the Medicare reimbursement rate. Physician specialties being targeted by Guidant as users of carotid stents include interventional radiologists, vascular surgeons, interventional cardiologists and interventional neuroradiologists.

Another segment of the vascular device market now undergoing rapid development is stent-grafts for use in a variety of applications including aneurysm treatment, improvement of patency in dialysis access grafts and cerebral vessels, and treatment of biliary strictures. A major advance in stent grafts was described by Ziv Haskal, MD, of New York Presbyterian Hospital (New York) at the SIR meeting using the Fluency device developed by Bard Peripheral Vascular (Tempe, Arizona) in dialysis access grafts. More than 250,000 Medicare patients undergo hemodialysis each year in the U.S., a number that is increasing by about 7% annually. By 2020, an estimated 2 million patients per year will undergo hemodialysis worldwide. A large percentage of those patients have synthetic access grafts implanted in their arm to allow routine dialysis treatment.

About half of patients with a synthetic graft will experience graft thrombosis each year, resulting in a need for repeated angioplasty procedures to restore blood flow through the graft. In a study involving 190 patients led by Haskal, the Fluency stent-graft was used to restore patency in 97 patients as an alternative to balloon angioplasty, with highly positive results. A total of 128 stent-grafts were implanted, and 54% of the stent-grafts remained patent at six months vs. 29% of the grafts treated with angioplasty. Primary patency of the access circuit at six months was 41% vs. 26%. The results could drive a significant expansion of the stent-graft market due to the large and growing number of patients with graft thrombosis and the high cost of maintaining graft patency with existing techniques.

Stent-grafts also are finding increased use in the treatment of abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs). Leading suppliers of stent-grafts for AAA and TAA repair include Medtronic (Minneapolis); W.L. Gore (Flagstaff, Arizona), with the Excluder and TAG devices; and Cook (Bloomington, Indiana). About 43,000 AneuRx stent grafts from Medtronic had been implanted worldwide as of January 2005. In addition, 25,000 Medtronic Talent stent-grafts have been implanted in Europe, and about 10,000 Cook Zenith devices have been implanted worldwide.

The most recent results from clinical studies indicate that procedural mortality is significantly lower with stent-grafts for treatment of AAA as compared to surgery, although there is a higher rate of secondary procedures for stent-grafts. Problems with current-generation devices include endoleaks in 13.9% of implanted grafts at four-year follow-up (for the AneuRx device) and a low (3.3%) but nevertheless significant rate of aneurysm rupture in spite of stent-graft implantation. Most significantly, the latest data from the FDA shows mortality rates increasing over time for stent-graft patients, crossing over the rate for surgically treated patients at about seven years post-procedure.

As discussed by David Williams, MD, of University of Michigan Hospital (Ann Arbor) at the SIR sessions, future generation stent-grafts must have smaller sheath profiles, greater flexibility and more controlled delivery characteristics to reduce trauma and embolisms occurring during implantation, and must also have features allowing more precise placement. In addition, new devices should be designed to provide higher radial force at anchoring sites, and provide improved fit to the vascular anatomy, particularly for TAA applications, in order to avoid graft migration and endoleaks.

Gore received FDA approval for its TAG stent-graft in December 2004, the first such device to enter the market in the U.S. However, both Medtronic and Cook are about to start clinical trials with new stent-grafts for TAA applications, including the Zenith TX2 from Cook and the Talent TAA graft from Medtronic.