Stent assembly for the treatment of vulnerable plaque

The present invention relates to vascular repair devices, and in particular to intravascular stents, which are adapted to be implanted into a patient\'s body lumen, such as a blood vessel or coronary artery, for the treatment of unstable or vulnerable, human atherosclerotic plaque.

Currently, the treatment of unstable or vulnerable plaque presents a significant therapeutic challenge to medical investigators. Vulnerable plaque is characterized by a basic lesion which is a raised plaque beneath the innermost arterial layer, the intima. Atherosclerotic plaques are primarily composed of varying amounts of long chain extracellular matrix (ECM) proteins that are synthesized by smooth muscle cells. The other primary lesion component of atherosclerotic plaque includes lipoproteins, existing both extracellularly and within foam cells derived primarily from lipid-laden macrophages. In a more advanced lesion, a necrotic core may develop, consisting of lipids, foam cells, cell debris, and cholesterol crystals, and myxomatous configurations with crystalline lipid forms. The necrotic core is rich in tissue factor and quite thrombogenic, but in the stable plaque it is protected from the luminal blood flow by a robust fibrous cap composed primarily of long chain ECM proteins, such as elastin and collagen, which maintain the strength of the fibrous cap. The aforementioned plaque represents the most common form of vulnerable plaque, known as a fibroatheroma. Histology studies from autopsy suggest this form constitutes the majority of vulnerable plaques in humans. A second form of vulnerable plaque represents a smaller fraction of the total, and these are known as erosive plaques. Erosive plaques generally have a smaller content of lipid, a larger fibrous tissue content, and varying concentrations of proteoglycans. Various morphologic features that have been associated with vulnerable plaque, include thinned or eroded fibrous caps or luminal surfaces, lesion eccentricity, proximity of constituents having very different structural moduli, and the consistency and distribution of lipid accumulations. With the rupture of fibroatheroma forms of vulnerable plaque, the luminal blood becomes exposed to tissue factor, a highly thrombogenic core material, which can result in total thrombotic occlusion of the artery. In the erosive form of vulnerable plaque, mechanisms of thrombosis are less understood but may still yield total thrombotic occlusion.

Although rupture of the fibrous cap in a fibroatheroma is a major cause of myocardial infarction (MI) related deaths, there are currently no therapeutic strategies in place to treat lesions that could lead to acute MI. The ability to detect vulnerable plaques and to treat them successfully with interventional techniques before acute MI occurs has long been an elusive goal. Numerous finite element analysis (FEA) studies have proved that, in the presence of a soft lipid core, the fibrous cap shows regions of high stresses. Representative of these studies include the following research articles, each of which are incorporated in their entirety by reference herein: Richardson et al. (1989), Influence of Plaque Configuration and Stress Distribution on Fissuring of Coronary Atherosclerotic Plaques, Lancet, 2(8669), 941-944; Loree et al. (1992), Effects of Fibrous Cap Thickness on Circumferential Stress in Model Atherosclerotic Vessels, Circulation Research, 71, 850-858; Cheng et al. (1992), Distribution of Circumferential Stress in Ruptured and Stable Atherosclerotic Lesions: A Structural Analysis With Histopathological Correlation, Circulation, 87, 1179-1187; Veress et al. (1993), Finite Element Modeling of Atherosclerotic Plaque, Proceedings of IEEE Computers in Cardiology, 791-794; Lee et al. (1996), Circumferential Stress and Matrix Metalloproteinase 1 in Human Coronary Atherosclerosis: Implications for Plaque Rupture, Atherosclerosis Thrombosis Vascular Biology, 16, 1070-1073; Vonesh et al. (1997), Regional Vascular Mechanical Properties by 3-D Intravascular Ultrasound Finite-Element Analysis, American Journal of Physiology, 272, 425-437; Beattie et al. (1999), Mechanical Modeling: Assessing Atherosclerotic Plaque Behavior and Stability in Humans, International Journal of Cardiovascular Medical Science, 2(2), 69-81; and Feezor et al. (2001), Integration of Animal and Human Coronary Tissue Testing with Finite Element Techniques for Assessing Differences in Arterial Behavior, BED-Vol. 50, 2001 Bioengineering Conference, ASME 2001. Further, these studies have indicated that such high stress regions correlate with the observed prevalence of locations of cap fracture. Moreover, it has been shown that subintimal structural features such as the thickness of the fibrous cap and the extent of the lipid core, rather than stenosis severity are critical in determining the vulnerability of the plaque. The rupture of a highly stressed fibrous cap can be prevented by using novel, interventional, therapeutic techniques such as specially designed stents that redistribute and lower the stresses in the fibrous cap.

Stents are generally tubular-shaped devices which function to hold open a segment of a blood vessel, coronary artery, or other body lumen. They are particularly suitable for use to support and hold back a dissected arterial lining which can occlude the fluid passageway therethrough.

Various means have been described to deliver and implant stents. One method frequently described for delivering a stent to a desired intraluminal location includes mounting the expandable stent on an expandable member, such as a balloon, provided on the distal end of an intravascular catheter, advancing the catheter to the desired location within the patient\'s body lumen, inflating the balloon on the catheter to expand the stent into a permanent expanded condition and then deflating the balloon and removing the catheter. One of the difficulties encountered using prior art stents involved maintaining the radial rigidity needed to hold open a body lumen while at the same time maintaining the longitudinal flexibility of the stent to facilitate its delivery. Once the stent is mounted on the balloon portion of the catheter, it is often delivered through tortuous vessels, including tortuous coronary arteries. The stent must have numerous properties and characteristics, including a high degree of flexibility, in order to appropriately navigate the tortuous coronary arteries. This flexibility must be balanced against other features including radial strength once the stent has been expanded and implanted in the artery. While other numerous prior art stents have had sufficient radial strength to hold open and maintain the patency of a coronary artery, they have lacked the flexibility required to easily navigate tortuous vessels without damaging the vessels during delivery.

Generally speaking, most prior art intravascular stents are formed from a metal such as stainless steel, which is balloon expandable and plastically deforms upon expansion to hold open a vessel. The component parts of these types of stents typically are all formed of the same type of metal, i.e., stainless steel. Other types of prior art stents may be formed from a polymer, again all of the component parts being formed from the same polymer material. These types of stents, the ones formed from a metal and the ones formed from a polymer, each have advantages and disadvantages. One of the advantages of the metallic stents is their high radial strength once expanded and implanted in the vessel. A disadvantage may be that the metallic stent lacks flexibility which is important during the delivery of the stent to the target site. With respect to polymer stents, they may have a tendency to be quite flexible and are advantageous for use during delivery through tortuous vessels, however, such polymer stents may lack the radial strength necessary to adequately support the lumen once implanted into an occlusive fibromuscular lesion of 70% stenosis or greater.

What has been needed and heretofore unavailable is a stent that can be used to treat a vulnerable plaque by reducing the cap stresses. The present invention satisfies this need and others.

The present invention is directed to an intravascular stent assembly that can be used to treat a lesion with vulnerable plaque by reducing the cap stresses. The invention also includes methods of making an intravascular stent assembly for the treatment of vulnerable plaque within an artherosclerotic artery and methods of using the stent assembly for the treatment of the same.

The stent assembly embodying features of the invention can be readily delivered to the desired body lumen, such as a coronary artery (peripheral vessels, bile ducts, etc.), by mounting the stent assembly on an expandable member of a delivery catheter, for example a balloon, and advancing the catheter and stent assembly through the body lumen to the target site. Generally, the stent is compressed or crimped onto the balloon portion of the catheter so that the stent assembly does not move longitudinally relative to the balloon portion of the catheter during delivery through the arteries, and during expansion of the stent at the target site. The stent is relatively flexible along its longitudinal axis to facilitate delivery through tortuous body lumens yet is stiff and stable enough radially in an expanded condition to maintain the patency of a body lumen such as an artery when implanted therein.

In one embodiment, the stent assembly of the invention generally includes a polymeric sleeve portion in a tubular configuration having first and second ends, wherein the first end is attached to a distal end region of a first stent and the second end is attached to a proximal end region of a second stent. The first and second stents of the stent assembly include a plurality of radially expandable cylindrical rings which are relatively independent in their ability to expand and to flex relative to one another. The individual radially expandable cylindrical rings of the stent are formed from a metallic material and are aligned on a common longitudinal axis. The resulting stent assembly structure is a series of radially expandable cylindrical rings, which are spaced longitudinally close enough so that small dissections in the wall of a body lumen may be pressed back into position against the luminal wall, but not so close as to compromise the longitudinal flexibility of the stent assembly. The cylindrical rings are attached to each other by flexible links such that at least one flexible link attaches adjacent cylindrical rings. If desired, more than one link can be used to attach adjacent cylindrical rings.

In an alternative embodiment, the stent assembly of the present invention includes at least two polymeric sleeve portions that are interconnected by at least three separate stents to form the stent assembly.

In another embodiment, the metallic material forming the stent includes stainless steel, titanium, tantalum, nickel titanium, and cobalt-chromium. The polymer material forming the polymeric sleeve portion is taken from a select group of biodegradable, bioabsorbable polymers or those with drug eluting capability for appropriate therapeutic drugs. Examples of preferable therapeutic drugs include antiplatelets, anticoagulants, antifibrins, antithrombins, and antiproliferatives.

The polymeric sleeve portion of the stent assembly has a length in a range of about 1 to 20 mm, and a thickness in the range of about 0.001 to 0.010 inches. The thickness of the polymeric sleeve portion is preferably in the range of about 0.001 to 0.005 inch.

In another embodiment, the polymeric sleeve portion is in communication with each of the metallic portions of the first and second stents by being mechanically fastened thereto. A primer is disposed about the metallic portion of the first and second stents that contacts the polymeric sleeve portion. The medium by which the polymeric sleeve portion is attached to the metallic portion of the stent assembly involves the application of a silicone adhesive on the metallic portion that contacts the polymeric sleeve which is cured thereon. Further, the polymeric sleeve portion of the stent assembly can be optionally loaded with at least one therapeutic drug or agent. Alternatively, if at least three stents are used, then at least two polymer sleeve portions are mechanically fastened to each of the metallic portions of the first, second and third stents as described above.

In still another embodiment, at least two links, but preferably no more than three links, interconnect the separate stent sections, while being in direct communication with the polymer sleeve portion in order to provide additional support to the sleeve portion.

One method for making the stent assembly of the present invention for use in the treatment of vulnerable plaque includes providing a first metallic stent and a second metallic stent having a generally cylindrical shape, wherein both the first metallic stent and the second metallic stent have distal and proximal end regions. A primer is applied to the distal end region of the first metallic stent and to the proximal end region of the second metallic stent. A first end of a tubular sleeve preformed of a polymer material is fitted onto the distal end region of the first metallic stent and a second end of the sleeve onto the proximal end region of the second metallic stent. An adhesive (e.g., silicone) is then applied over the portion of the polymeric sleeve that contacts the metallic portion of the stent assembly. The polymeric sleeve is bonded to the metallic portions of both the first and second stents.

Preferably, the metallic materials forming the stent assembly consist of stainless steel, titanium, tantalum, nickel titanium, and cobalt-chromium. The polymer material forming the sleeve is preferably taken from a select group of biodegradable, bioabsorbable polymers or those with drug eluting capability for appropriate therapeutic drugs. Examples of preferable therapeutic drugs include antiplatelets, anticoagulants, antifibrins, antithrombins, and antiproliferatives.

The process by which the polymer sleeve is preferably bonded to the metallic portions of the stent assembly involves curing with heat. The stent assembly is cured in an oven at about 150° C. for about 15 minutes and then cooled down for about 5 to 20 minutes. The polymer sleeve can be optionally loaded with at least one therapeutic drug or agent.

Methods of using an intravascular stent assembly for treatment of a vulnerable plaque region within a body lumen are also provided herein.

Other features and advantages of the present invention will become more apparent from the following detailed description of the invention when taken in conjunction with the accoMPanying exemplary drawings.