Driving Development of Innovative Technologies in Vascular Intervention

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DOI
http://dx.doi.org/10.15420/ecr.2006.1.1s

BIOTRONIK (Buelach, Switzerland) is a member of the BIOTRONIK group, a leading European manufacturer of medical technology with a worldwide market presence. The company offers a complete line of products for diagnosis, treatment and advanced therapy support in cardiac rhythm management (CRM), electrophysiology and vascular intervention. BIOTRONIK has been active in the field of vascular intervention since 1994 and has progressively strengthened its position through focusing development efforts on innovative technologies with superior quality. The vascular intervention portfolio comprises guidewires, balloon catheters and stent systems for coronary and peripheral applications. Over the past 12 years, BIOTRONIK have introduced a multitude of innovative coronary and peripheral interventional products and a promising future pipeline packed full of new innovations lies ahead.

Recently, the PRO-Kinetic cobalt chromium coronary stent was launched globally and has been extremely well received, rapidly achieving double digit share in this market segment.1 The PROKinetic stent combines the advantages of low profile, exceptional deliverability and a silicon carbide (PROBIO®) passive coating to ensure optimal clinical outcomes. In terms of drug-eluting stents (DES), BIOTRONIK is developing the PRO-Kinetic platform in combination with the drug pimecrolimus and a bioabsorbable polymer.

Currently, BIOTRONIK serves the DES market by being the exclusive distributor of the CE-Marked CoStar™ Paclitaxel-eluting stent in Europe, Latin America and certain countries in Asia. Additionally, BIOTRONIK has released the new Cruiser guidewire, the Elect balloon and Hyperflow angiographic catheters for the coronary market. In terms of products for the peripheral market, BIOTRONIK introduced the unique, 4Fr Astron PULSAR stent for superficial femoral artery (SFA) disease, which is the lowest profile, most flexible stent available to physicians for this complex indication. The Astron stent complements a strengthening portfolio of peripheral self-expandable and balloon-expandable stents and balloons.

The PRO-Kinetic stent is available outside the US and has been successful since it was CE-Marked in 2005. PRO-Kinetic has an innovative design of ultra-thin struts and high radial strength. Cobalt chromium has recently proved to be a revolutionary material for coronary stents. Various characteristics distinguish cobalt chromium compared with stainless steel, including improved vessel support and the ability to reduce strut thickness.

This has been proven to result in lower restenosis rates.2,3 Further advantages of the PRO-Kinetic include the double-helix design, which provides flexibility and reliable access to even the most distal vessels. PRO-Kinetic is also coated with PROBIO, which is intended to improve general haemocompatibility and the biocompatibility of a permanently implanted stent. PRO-Kinetic is indicated for the treatment of coronary arteries 2-5mm in diameter. A recent post-CE Mark registry of 174 patients demonstrated that it is possible for the stent to cross difficult lesions. Physician feedback to BIOTRONIK and to external research agencies highlight PRO-Kinetic as the new bare-metal stent of choice.

PRO-Kinetic will be a future platform for BIOTRONIKÔÇÖs next-generation DES, in combination with a bioabsorbable polymer and pimecrolimus. BIOTRONIK recently signed an agreement with Novartis Pharma AG, granting BIOTRONIK the right to evaluate pimecrolimus and the potential to obtain a worldwide, non-exclusive licence to develop, manufacture and commercialise such products. The drug, pimecrolimus, is a cell-selective inhibitor for the production and release of pro-inflammatory cytokines. Inflammation is believed to be one of the key mechanisms that cause restenosis via excess proliferation of vascular smooth muscle cells. Because pimecrolimus is not an anti-mitotic compound, it is believed not to inhibit re-endothelialisation, or the growth of the endothelial cells that line the interior surface and maintain the healthy function of blood vessels. This is an important potential advance compared with existing DES because there are still unmet needs in clinical areas, especially with challenging and high-risk patient populations.

BIOTRONIK launched the CoStar Paclitaxel-eluting Coronary Stent System, through a distribution agreement with the developer and manufacturer Conor Medsystems. The CoStar system is a logical choice for BIOTRONIK to distribute, because it is the first device to offer a bioabsorbable polymer as a mechanism for drug delivery and it fits with BIOTRONIKÔÇÖs overall strategy of delivering absorbable solutions. Other DES have traditionally utilised permanent polymers, which can cause inflammation when it comes into contact with the arterial wall in the long term. Additionally, because those polymers are non-bioabsorbable, they can retain much of the drug on the stent long after its therapeutic effects are required. It has been suggested that this has negative effects. The bioresorbable polymer used on the CoStar stent is fully absorbed by the body after the drug has been released, leaving no permanent residual polymers or drug traces. BIOTRONIK believes that the pursuit of absorbable solutions for treatment of vascular disease are the future for technology development and will ensure better outcomes in the long term.

BIOTRONIK has a new nitinol guidewire Cruiser. The Cruiser guidewire family is designed specifically for greater distal control during angioplasty procedures. The wire design, coupled with a nitinol core, contributes to its unique performance characteristics for reaching the target lesion and ensuring outstanding procedural outcomes. The wire is available in a variety of tip stiffness levels for different indications.

The Elect coronary balloon catheter has reduced shaft profiles allowing use of smaller guide catheters. A laser rounded soft tip with 0.017in lesion entry profile provides increased safety and crossing with all types of lesions. There is an extensive product range with 52 sizes including diameters 1.5-4.0mm and lengths 6-35mm. The Elect balloon catheter can be pushed, crossed and tracked; it is these characteristics that provide outstanding procedural performance.

In terms of coronary diagnostic catheters, BIOTRONIK offers the HyperFlow family, designed to deliver X-ray visible contrast fluids for digital subtraction angiography (DSA) overview and selective angiography. Exceptionally large internal diameters enable unmatched flow rates without compromising the handling characteristics. Coupling nylon with composite extrusion technology allows the torque and tracking to be of excellent quality. Catheters are available in 4Fr, 5Fr, and 6Fr, as well as a variety of curve shapes.

The BIOTRONIK peripheral portfolio is noted to be one of the most innovative offerings, especially because all stents are coated with PROBIO to improve haemocompatibility and biocompatibility, in addition to the launch of the 4Fr Astron PULSAR self-expanding stent system. Designed for stenting of the SFA, it is the only system available in diameter 7mm and length 80mm with 4Fr sheath compatibility. This device complements the Astron family, which is the larger range of self-expanding stents designed for treating iliac arteries. The Astron stents are 6Fr sheath compatible and incorporate an 'anti-jumpÔÇÖ system that allows for accurate and reliable release. The dynamic balloon-expandable stent has high flexibility due to its helical design and is intended for iliac and femoral arteries, with a broad range of 5-10mm diameter and 15-56mm length. The Pheron┬« balloon is designed for peripheral angioplasty and is available in 3-10mm diameter and 20-100mm length. Pheron is a proven, durable and reliable balloon with rapid deflation time and shaft flexibility.

BIOTRONIK has invested significantly in the development of absorbable metal technologies, and is pursuing engineering and research activities on stents made from this material in both coronary and peripheral applications. The absorbable metal stent (AMS) represents a revolutionary leap forward in the treatment of vascular disease and is an alternative to conventional metal stenting. The AMS was designed to benefit patients and physicians on several levels, including treating patients who otherwise might not be candidates for a permanent stent and enabling re-intervention on stented vessels, a procedure that currently is not possible in the majority of cases. Both human and animal trials of the AMS have achieved outstanding results to date. In the peripheral setting, the BEST-BTK experience revealed excellent safety and efficacy of the AMS at 24 months in patients with critical limb ischaemia (CLI) and below-the-knee lesions. Limb salvage was 94.7% and primary patency was 73.3%, these results are considered to be extremely promising in a challenging patient population. The experience confirmed that the AMS could be successfully delivered to the lesion, it provided good vessel scaffolding, was completely magnetic resonance imaging ((MRI)-compatible) and absorbed as intended. Initial results of the coronary PROGRESS-AMS study confirm the safety and feasibility of the AMS in coronary vessels, with zero non-fatal myocardial infarctions (MI), zero deaths and zero stent thrombosis. The trial did reveal a rate of restenosis in line with bare-metal stent standards. Additional fine-tuning will occur in AMS development for the coronary indication, including the addition of a drug and bioabsorbable polymer.

The goal of the BIOTRONIK DES absorbable metal project is to combine the benefits of pimecrolimus with a proven deliverable stent platform and an absorbable material that lasts as long as it is needed to support the treated vessel through the healing process and then allows the artery to regain its vasomotoric properties. Animal studies for this platform are currently in progress.

A noteworthy point is BIOTRONIKÔÇÖs announced partnership with Micrus Endovascular Corporation. BIOTRONIK has entered the neurovascular interventional marketplace as the manufacturer of the Pharos stent for treatment of ischaemic and haemorrhagic stroke. Micrus Endovascular is the marketer and distributor of the Pharos stent.

BIOTRONIK aims to offer competitive vascular interventional technologies that allow physicians to offer the best therapeutic options to their patients, either through internal development and release, or by fostering innovative partnerships with companies who have complementary strategies of offering the best and most relevant products. With over 2,800 employees and a global network spanning all continents, BIOTRONIK is a company that is focused on restoring patient quality of life, through driving the development and commercialisation of innovative technologies in partnership with their customers. Ôûá

References
  1. Dodds M, Conor Aims for a Spot on the Podium, Citigroup Mulit-Company Note, Medical Supplies & Technology, JIM Wrap (2006).
  2. Kastrati A , Mehilli J et al., Intracoronary Stenting and Angiographic Results Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO) Trial, Circulation (2001);103: pp. 2,816-2,821.
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  3. Pache J, Kastrati A et al., Intracoronary Stenting and Angiographic Results: Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO-2) Trial, J Am Coll Cardiol (2003);41: pp. 1,283-1,288.
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