A dual therapy stent is a

coronary artery stent A coronary stent is a tube-shaped device placed in the coronary arteries that supply blood to the heart, to keep the arteries open in the treatment of coronary heart disease. It is used in a procedure called percutaneous coronary intervention (P ...

that combines the technology of an

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

-coated

stent In medicine, a stent is a metal or plastic tube inserted into the lumen of an anatomic vessel or duct to keep the passageway open, and stenting is the placement of a stent. A wide variety of stents are used for different purposes, from expandab ...

and a

drug-eluting stent A drug-eluting stent (DES) is a peripheral or coronary stent (a scaffold) placed into narrowed, diseased peripheral or coronary arteries that slowly release a drug to block cell proliferation. This prevents fibrosis that, together with clots ( ...

. Currently, second-generation

s require long-term use of dual-antiplatelet therapy, which increases the risk of major bleeding occurrences in patients. Compared to drug-eluting stents, dual therapy stents have improved vessel regeneration and cell proliferation capabilities. As a result, dual therapy stents were developed to reduce the long-term need for dual-antiplatelet therapy. The COMBO stent is the first and only dual therapy stent that addresses the challenges of vessel healing in drug-eluting stents. This stent is an anti-CD34 antibody-coated and

sirolimus Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosi ...

-eluting bioresorbable stent. The COMBO stent combines the

Genous Genous is an endothelial progenitor cell (EPC) capture technology manufactured by OrbusNeich that promotes the accelerated natural healing of the vessel wall after stent implantation. The pro-healing technology has an antibody surface coating that c ...

stent's endothelial cell capture technology with an antiproliferative, biodegradable

drug elution. The COMBO stent has received CE Mark approval.

History and Problems of Coronary Artery Stents

The field of

interventional cardiology Interventional cardiology is a branch of cardiology that deals specifically with the catheter based treatment of structural heart diseases. Andreas Gruentzig is considered the father of interventional cardiology after the development of angioplast ...

began in the 20th century with the development of the plain old balloon angioplasty. However, this procedure carried risks of promoting

platelet aggregation Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

, tearing, arterial recoil, and

restenosis Restenosis is the recurrence of stenosis, a narrowing of a blood vessel, leading to restricted blood flow. Restenosis usually pertains to an artery or other large blood vessel that has become narrowed, received treatment to clear the blockage and s ...

. Thus, coronary artery stents were created to prevent

after balloon dilation. There are three types of stents: bare-metal stents (BMS),

s (DES), and bioresorbable vascular scaffolds (BRS). The first stents created were bare-metal stents where they were made from stainless steel and had poor flexibility. Despite its reduced rates of

compared to plain old balloon angioplasty, it still had high rates o
stent thrombosis
and required a high dosage of

blood thinners Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...

. This led to the development of

s to act as local drug delivery and vascular scaffold platform to reduce in-stent restenosis. Antiproliferative drugs like

and

paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical canc ...

were used in the first-generation

s to inhibit the migration of vascular smooth muscle cells and

.Dual-Therapy Stenting: The Next Step in the Evolution of Stent Design (Cardiology Today: Intervention)
/ref> The first implanted

occurred in 1999, which revolutionized the course of

. However, despite the

s superiority over the

bare-metal stent A bare-metal stent is a stent made of thin, uncoated (bare) metal wire that has been formed into a mesh-like tube. The first stents licensed for use in cardiac arteries were bare metal – often 316L stainless steel. More recent "second generation ...

s, drug-eluting stent implantation had possible concerns over

and significant

blood clotting Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanis ...

in a localized area. As a result, improvements in the stent material, strut thickness, polymer, and drug choice led to the development of second-generation drug-eluting stents that showcased overall clinical enhancements to its predecessor. The new stent used more biocompatible molecules like zotarolimus and

everolimus Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours. It is the 40 ...

with quicker drug elution. However, despite these improvements, concerns persisted on the risk of stent thrombosis.

Risks in Drug-Eluting Stents

The development of dual therapy stents resulted from the health risks of long-term use of dual antiplatelet therapy from drug-eluting stents.

Drug-eluting stent A drug-eluting stent (DES) is a peripheral or coronary stent (a scaffold) placed into narrowed, diseased peripheral or coronary arteries that slowly release a drug to block cell proliferation. This prevents fibrosis that, together with clots ( ...

s inhibit the growth of

endothelial cells The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

and vascular smooth muscle cells, which are essential for in-stent endothelialization. Due to inhibition of vital vascular system cells, this causes risk of stent thrombosis, and, thus, patients with

s are required to use dual antiplatelet therapy for approximately 12 months. Although long term use of dual antiplatelet therapy research showcases reduced risk of cardiovascular deaths, it has increased occurrences of major bleeding events, which has challenges for patients with bleeding disorders.

Clinical Applications of Dual Therapy Stents

The COMBO dual therapy stent is the first and only dual therapy stent presently developed. The COMBO dual therapy stent combines the anti-CD34 antibody coating of the Genous Stent with antiproliferative

elution. The

drug reduces the risk of stent restenosis through inhibiting the formation of

neointima Neointima typically refers to scar tissue that forms within tubular anatomical structures such as blood vessels, as the intima is the innermost lining of these structures. Neointima can form as a result of vascular surgery such as angioplasty ...

while the anti-CD34 antibody coating reverses the inhibition of local

from the

elution.

Genous Stent

The predecessor of the biotechnology used to create a dual therapy stent was the development of the Genous stent. The Genous stent is a coronary artery stent coated with anti-CD3 monoclonal antibodies that bind with circulating endothelial cells to the stent. The coated stent promotes the formation of an endothelial layer, which protects against

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (t ...

and reduces

. Furthermore, the Genous stent promotes coronary vascular repair response and reduces neointimal hyperplasia after stent implantation. Although the Genous stent promotes rapid vessel healing, it did not decrease the rate of target lesion failure compared to

s, which increases the risk of

and

failure.

COMBO Dual Therapy Stent

The COMBO stent is a pro-healing stent with

drug elution and anti-CD3 monoclonal antibodies that has enhanced degree of endothelization. The stent has an abluminal, facing vessel wall, bioabsorbable coating that continuously releases

and a luminal anti-CD34 antibody cell capture coating. The COMBO stent's enhanced endothelization is due to the

drug that reduces the risk of stent

and the Genous stent's anti-CD3 antibodies capture biotechnology. The COMBO stent reduces not only the rate of stent restenosis but also the need for dual antiplatelet therapy, which enables high-risk patient groups like patients who are under long-term anticoagulation regimens or patients with bleeding disorders to use this type of stent.

References

{{Reflist

External links

The COMBO Dual Therapy Stent
Interventional cardiology Drug delivery devices Biological engineering