Dual therapy stent

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A dual therapy stent is a coronary artery stent that combines the technology of an antibody-coated stent and a drug-eluting stent. [1] Currently, second-generation drug-eluting stents require long-term use of dual-antiplatelet therapy, which increases the risk of major bleeding occurrences in patients. [2] Compared to drug-eluting stents, dual therapy stents have improved vessel regeneration and cell proliferation capabilities. [1] [2] As a result, dual therapy stents were developed to reduce the long-term need for dual-antiplatelet therapy. [3]

Contents

The COMBO stent is the first and only dual therapy stent that addresses the challenges of vessel healing in drug-eluting stents. [4] This stent is an anti-CD34 antibody-coated and sirolimus-eluting bioresorbable stent. [2] The COMBO stent combines the Genous stent's endothelial cell capture technology with an antiproliferative, biodegradable sirolimus drug elution. [5] The COMBO stent has received CE Mark approval. [6]

History and Problems of Coronary Artery Stents

The field of interventional cardiology began in the 20th century with the development of the plain old balloon angioplasty. [4] However, this procedure carried risks of promoting platelet aggregation, tearing, arterial recoil, and restenosis. [4] Thus, coronary artery stents were created to prevent restenosis after balloon dilation. [4] There are three types of stents: bare-metal stents (BMS), drug-eluting stents (DES), and bioresorbable vascular scaffolds (BRS). [4]

The first stents created were bare-metal stents where they were made from stainless steel and had poor flexibility. Despite its reduced rates of restenosis compared to plain old balloon angioplasty, it still had high rates of stent thrombosis and required a high dosage of blood thinners. [4] This led to the development of drug-eluting stents to act as local drug delivery and vascular scaffold platform to reduce in-stent restenosis. [4]

Antiproliferative drugs like sirolimus and paclitaxel were used in the first-generation drug-eluting stents to inhibit the migration of vascular smooth muscle cells and restenosis. [4] [1] The first implanted drug-eluting stent occurred in 1999, which revolutionized the course of interventional cardiology. [1] However, despite the drug-eluting stents superiority over the bare-metal stents, drug-eluting stent implantation had possible concerns over platelet aggregation and significant blood clotting in a localized area. [1]

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. [4] [1] The new stent used more biocompatible molecules like zotarolimus and everolimus with quicker drug elution. [4] 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. [2] Drug-eluting stents inhibit the growth of endothelial cells and vascular smooth muscle cells, which are essential for in-stent endothelialization. [1] Due to inhibition of vital vascular system cells, this causes risk of stent thrombosis, and, thus, patients with drug-eluting stents are required to use dual antiplatelet therapy for approximately 12 months. [2] 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. [2]

Clinical Applications of Dual Therapy Stents

The COMBO dual therapy stent is the first and only dual therapy stent presently developed. [1] The COMBO dual therapy stent combines the anti-CD34 antibody coating of the Genous Stent with antiproliferative sirolimus elution. [1] The sirolimus drug reduces the risk of stent restenosis through inhibiting the formation of neointima while the anti-CD34 antibody coating reverses the inhibition of local endothelial cells from the sirolimus elution. [1]

Genous Stent

The predecessor of the biotechnology used to create a dual therapy stent was the development of the Genous stent. [1] The Genous stent is a coronary artery stent coated with anti-CD3 monoclonal antibodies that bind with circulating endothelial cells to the stent. [7] The coated stent promotes the formation of an endothelial layer, which protects against thrombosis and reduces restenosis. [7] Furthermore, the Genous stent promotes coronary vascular repair response and reduces neointimal hyperplasia after stent implantation. [8] Although the Genous stent promotes rapid vessel healing, it did not decrease the rate of target lesion failure compared to drug-eluting stents, which increases the risk of restenosis and stent failure. [8] [9]

COMBO Dual Therapy Stent

The COMBO stent is a pro-healing stent with sirolimus drug elution and anti-CD3 monoclonal antibodies that has enhanced degree of endothelization. [10] The stent has an abluminal, facing vessel wall, bioabsorbable coating that continuously releases sirolimus and a luminal anti-CD34 antibody cell capture coating. [10]

The COMBO stent's enhanced endothelization is due to the sirolimus drug that reduces the risk of stent restenosis and the Genous stent's anti-CD3 antibodies capture biotechnology. [8] 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. [1]

See also

Related Research Articles

<span class="mw-page-title-main">Angioplasty</span> Procedure to widen narrow arteries or veins

Angioplasty, also known as balloon angioplasty and percutaneous transluminal angioplasty (PTA), is a minimally invasive endovascular procedure used to widen narrowed or obstructed arteries or veins, typically to treat arterial atherosclerosis.

An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where classical Vitamin K antagonist anticoagulants have minimal effect.

<span class="mw-page-title-main">Stent</span> Type of medical device

In medicine, a stent is a tube usually constructed of a metallic alloy or a polymer. It is inserted into the lumen of an anatomic vessel or duct to keep the passageway open. Stenting refers to the placement of a stent. The word "stent" is also used as a verb to describe the placement of such a device, particularly when a disease such as atherosclerosis has pathologically narrowed a structure such as an artery.

<span class="mw-page-title-main">Sirolimus</span> Pharmaceutical drug

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 lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumor (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mechanistic target of rapamycin (mTOR) kinase inhibitor that reduces the sensitivity of T cells and B cells to interleukin-2 (IL-2), inhibiting their activity.

<span class="mw-page-title-main">Coronary catheterization</span> Radiography of heart and blood vessels

A coronary catheterization is a minimally invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It is performed for both diagnostic and interventional (treatment) purposes.

<span class="mw-page-title-main">Restenosis</span> Recurrence of stenosis, a narrowing of a blood vessel

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 subsequently become renarrowed. This is usually restenosis of an artery, or other blood vessel, or possibly a vessel within an organ.

<span class="mw-page-title-main">Interventional cardiology</span> Catheter-based treatment of structural heart diseases

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<span class="mw-page-title-main">Endothelial dysfunction</span>

In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining vascular tone and regulating oxidative stress by releasing mediators, such as nitric oxide, prostacyclin and endothelin, and controlling local angiotensin-II activity.

<span class="mw-page-title-main">Percutaneous coronary intervention</span> Medical techniques used to manage coronary occlusion

Percutaneous coronary intervention (PCI) is a minimally invasive non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The procedure is used to place and deploy coronary stents, a permanent wire-meshed tube, to open narrowed coronary arteries. PCI is considered 'non-surgical' as it uses a small hole in a peripheral artery (leg/arm) to gain access to the arterial system, an equivalent surgical procedure would involve the opening of the chest wall to gain access to the heart area. The term 'coronary angioplasty with stent' is synonymous with PCI. The procedure visualises the blood vessels via fluoroscopic imaging and contrast dyes. PCI is performed by an interventional cardiologists in a catheterization laboratory setting.

<span class="mw-page-title-main">Drug-eluting stent</span> Medical implant

A drug-eluting stent (DES) is a self-expanding tube made of a mesh-like material used to treat narrowed arteries (stenosis) in medical procedures. It is inserted into a narrowed artery using a balloon. Once the balloon inside the stent is inflated, the stent expands, pushing against the artery wall. The mesh design allows cells to grow through and around it, securing it in place. The stent slowly releases a drug to prevent re-blockage of the artery. The release of the drug from the stent to prevent the growth of scar tissue and reduce the risk of stent restenosis, which is the narrowing of the stented area of an artery after treatment. A drug-eluting stent is different from other types of stents because it has a coating that delivers medication directly to the arterial wall. A DES is often made of metal alloys and can be inserted into blocked or narrowed arteries through a catheter placed in a peripheral artery, such as in the arm or leg. DES is fully integrated with a catheter delivery system and is viewed as one integrated medical device.

Phosphorylcholine is the hydrophilic polar head group of some phospholipids, which is composed of a negatively charged phosphate bonded to a small, positively charged choline group. Phosphorylcholine is part of the platelet-activating factor; the phospholipid phosphatidylcholine and sphingomyelin, the only phospholipid of the membrane that is not built with a glycerol backbone. Treatment of cell membranes, like those of RBCs, by certain enzymes, like some phospholipase A2, renders the phosphorylcholine moiety exposed to the external aqueous phase, and thus accessible for recognition by the immune system. Antibodies against phosphorylcholine are naturally occurring autoantibodies that are created by CD5+/B-1 B cells and are referred to as non-pathogenic autoantibodies.

The history of invasive and interventional cardiology is complex, with multiple groups working independently on similar technologies. Invasive and interventional cardiology is currently closely associated with cardiologists, though the development and most of its early research and procedures were performed by diagnostic and interventional radiologists.

<span class="mw-page-title-main">Coronary stent</span> Medical stent implanted into coronary arteries

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 patients suffering from coronary heart disease. The vast majority of stents used in modern interventional cardiology are drug-eluting stents (DES). They are used in a medical procedure called percutaneous coronary intervention (PCI). Coronary stents are divided into two broad types: drug-eluting and bare metal stents. As of 2023, drug-eluting stents were used in more than 90% of all PCI procedures. Stents reduce angina and have been shown to improve survival and decrease adverse events after a patient has suffered a heart attack—medically termed an acute myocardial infarction.

<span class="mw-page-title-main">Zotarolimus</span> Chemical compound

Zotarolimus is an immunosuppressant. It is a semi-synthetic derivative of sirolimus (rapamycin). It was designed for use in stents with phosphorylcholine as a carrier. Zotarolimus, or ABT-578, was originally used on Abbott's coronary stent platforms to reduce early inflammation and restenosis; however, Zotarolimus failed Abbott's primary endpoint to bring their stent/drug delivery system to market. The drug was sold/distributed to Medtronic for use on their stent platforms, which is the same drug they use today. Coronary stents reduce early complications and improve late clinical outcomes in patients needing interventional cardiology. The first human coronary stent implantation was first performed in 1986 by Puel et al. However, there are complications associated with stent use, development of thrombosis which impedes the efficiency of coronary stents, haemorrhagic and restenosis complications are problems associated with stents.

<span class="mw-page-title-main">Bare-metal stent</span>

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" bare-metal stents have been made of cobalt chromium alloy. While plastic stents were first used to treat gastrointestinal conditions of the esophagus, gastroduodenum, biliary ducts, and colon, bare-metal stent advancements led to their use for these conditions starting in the 1990s.

<span class="mw-page-title-main">Cangrelor</span> Chemical compound

Cangrelor, sold under the brand name Kengreal among others, is a P2Y12 inhibitor FDA approved as of June 2015 as an antiplatelet drug for intravenous application. Some P2Y12 inhibitors are used clinically as effective inhibitors of adenosine diphosphate-mediated platelet activation and aggregation. Unlike clopidogrel (Plavix), which is a prodrug, cangrelor is an active drug not requiring metabolic conversion.

<span class="mw-page-title-main">Bioresorbable stent</span> Medical stent that dissolves or is absorbed by the body

A bioresorbable stent is a tube-like device (stent) that is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. It is made from a material that can release a drug to prevent scar tissue growth. It can also restore normal vessel function and avoid long-term complications of metal stents.

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 captures circulating CD34+ endothelial progenitor cells to the device, forming a functional endothelial layer over the stent to protect against thrombus and minimize restenosis.

Neointimal hyperplasia refers to proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in the thickening of arterial walls and decreased arterial lumen space. Neointimal hyperplasia is the major cause of restenosis after percutaneous coronary interventions such as stenting or angioplasty. The term neointima is used because the cells in the hyperplastic regions of the vascular wall have histological characteristics of both intima and normal artery cells.

Alfredo E. Rodríguez is an Argentine interventional cardiologist, clinical researcher, and author. He is the Chief of Interventional Cardiology Service at Otamendi Hospital and Director and Founder of the Cardiovascular Research Center (CECI) a non -profit Research Organization in Buenos Aires Argentina.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 Dual-Therapy Stenting: The Next Step in the Evolution of Stent Design (Cardiology Today: Intervention)
  2. 1 2 3 4 5 6 Howard, Charles E.; Nambi, Vijay; Jneid, Hani; Khalid, Umair (2019-10-15). "Extended Duration of Dual‐Antiplatelet Therapy After Percutaneous Coronary Intervention: How Long Is Too Long?". Journal of the American Heart Association. 8 (20): e012639. doi:10.1161/JAHA.119.012639. PMC   6818039 . PMID   31576769.
  3. ↑ Baldetti, Luca; Beneduce, Alessandro; Gramegna, Mario; Colombo, Antonio; Giannini, Francesco (2018). "The dual-therapy COMBO stent: a rationale for a light dual antiplatelet therapy treatment". Future Cardiology. 14 (6): 471–482. doi:10.2217/fca-2018-0051. ISSN   1744-8298. PMID   30480466. S2CID   53730585.
  4. 1 2 3 4 5 6 7 8 9 10 Tomberli, Benedetta; Mattesini, Alessio; Baldereschi, Giorgio Iacopo; Di Mario, Carlo (2018-05-01). "A Brief History of Coronary Artery Stents". Revista Española de Cardiología (English Edition). 71 (5): 312–319. doi:10.1016/j.rec.2017.11.022. ISSN   1885-5857. PMID   29361499.
  5. ↑ Baldetti, Luca; Beneduce, Alessandro; Gramegna, Mario; Colombo, Antonio; Giannini, Francesco (2018-11-01). "The dual-therapy COMBO stent: a rationale for a light dual antiplatelet therapy treatment". Future Cardiology. 14 (6): 471–482. doi:10.2217/fca-2018-0051. ISSN   1479-6678. PMID   30480466. S2CID   53730585.
  6. ↑ "First Dual-Therapy Stent Nets CE Mark". www.healio.com. Retrieved 2021-11-17.
  7. 1 2 Beijk, Marcel A.M.; Klomp, Margo; Verouden, Niels J.W.; van Geloven, Nan; Koch, Karel T.; Henriques, José P.S.; Baan, Jan; Vis, Marije M.; Scheunhage, Esther; Piek, Jan J.; Tijssen, Jan G.P. (May 2010). "Genous™ endothelial progenitor cell capturing stent vs. the Taxus Liberté stent in patients with de novo coronary lesions with a high-risk of coronary restenosis: a randomized, single-centre, pilot study". European Heart Journal. 31 (9): 1055–1064. doi:10.1093/eurheartj/ehp476. ISSN   0195-668X. PMC   2862178 . PMID   19933225.
  8. 1 2 3 "Dual-Therapy Stenting: The Next Step in the Evolution of Stent Design". www.healio.com. Retrieved 2017-09-18.
  9. ↑ Konigstein, Maayan; Madhavan, Mahesh V.; Ben-Yehuda, Ori; Rahim, Hussein M.; Srdanovic, Iva; Gkargkoulas, Fotis; Mehdipoor, Ghazaleh; Shlofmitz, Evan; Maehara, Akiko; Redfors, Björn; Gore, Ankita K. (2019). "Incidence and predictors of target lesion failure in patients undergoing contemporary DES implantation—Individual patient data pooled analysis from 6 randomized controlled trials". American Heart Journal. 213: 105–111. doi:10.1016/j.ahj.2019.03.011. ISSN   0002-8703. PMC   7051011 . PMID   31132582.
  10. 1 2 Granada, Juan F.; Inami, Shigenobu; Aboodi, Michael S.; Tellez, Armando; Milewski, Krzysztof; Wallace-Bradley, David; Parker, Sherry; Rowland, Steve; Nakazawa, Gaku; Vorpahl, Marc; Kolodgie, Frank D. (2010-06-01). "Development of a Novel Prohealing Stent Designed to Deliver Sirolimus From a Biodegradable Abluminal Matrix". Circulation: Cardiovascular Interventions. 3 (3): 257–266. doi: 10.1161/CIRCINTERVENTIONS.109.919936 . PMID   20442358. S2CID   707177.
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