A drug-eluting stent (DES) is a peripheral or
coronary 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 (PC ...
(a scaffold) placed into narrowed, diseased peripheral or
coronary arteries
The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ of ...
that slowly release a
drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
to block
cell proliferation. This prevents
fibrosis
Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
that, together with clots (
thrombi
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...
), could otherwise block the stented artery, a process called
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 ...
. The stent is usually placed within the peripheral or coronary artery by an
interventional cardiologist
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 ...
or interventional radiologist during an
angioplasty
Angioplasty, is 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 atheroscle ...
procedure.
Drug-eluting stents in current clinical use were approved by the FDA after clinical trials showed they were statistically superior to
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 for the treatment of native coronary artery narrowings, having lower rates of major adverse cardiac events (usually defined as a composite clinical endpoint of death +
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
+ repeat intervention because of
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 ...
). The first drug-eluting stents to be approved in Europe and the U.S. were coated with
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 ...
or an
mTOR
The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MT ...
inhibitor, such as
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 ...
.
Indications
Considerations for use
It is crucial to identify patients who are good candidates for procedural intervention. Generally, patients without symptoms of coronary blockage or without evidence of ischemia (oxygen deprivation) on labs and imaging are not subjected to stent procedures, as the complications and risks of such a procedure would outweigh any potential benefit.
Procedural intervention, such as angioplasty or stent placement, is reserved for patients with clinical symptoms of coronary artery flow reduction or observable coronary artery obstruction on imaging.
This is otherwise known as a myocardial infarction (heart attack). These symptoms can include, but are not limited to:
* Severe, pressure-like chest pain unrelieved by rest
* Shortness of breath, fatigue, lightheadedness
* Palpitations
* Atypical symptoms: nausea, vomiting, indigestion, confusion, back pain
There are two major classifications of myocardial infarction (MI): ST-elevation MI vs. non-ST elevation. The
criteria for diagnosis are beyond the scope of this article, but it is important to note that stenting is considered first-line therapy for patients diagnosed with a STEMI.
Contraindications
The only absolute contraindication to stent placement is significant active bleeding. This is due primarily to the need for in-procedure anticoagulation and dual antiplatelet therapy during the recovery period.
Other considerations that could prevent the use of stents include a history of in-stent restenosis, bleeding diathesis (high susceptibility to bleed), complex or unsuitable coronary anatomy, and/or a short life expectancy due to other medical conditions.
Off-label use
Drug-eluting stents also have been shown to be superior to bare-metal stents in reducing short-term complications of stenting in
saphenous vein grafts; however, use in these bypass grafts is an example of "
off-label
Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
" use of drug-eluting stents. That is, this application has not been sufficiently examined by the
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
for that agency to recommend the use. For "on-label" applications, the FDA "believes that coronary drug-eluting stents remain safe and effective when used for the FDA-approved indications. These devices have significantly reduced the need for a second surgery to treat restenosis for thousands of patients each year."
[Dixon et a. Year in Interventional Cardiology JACC Vol. 53, No. 22, 2009]
Some concern has been expressed about the overzealous use of stents in general. Two studies found about half of patients received stents for unapproved reasons,
with worse outcomes for the patients in both studies. More recent data suggest off-label use of both bare-metal stents and drug-eluting stents has increased risks. However, drug-eluting stents seemed to have similar or improved rates of death or myocardial infarction compared with bare-metal stents, and consistently reduced the need for target vessel revascularization. Overall, the data support the use of drug-eluting stents for off-label indications.
Efficacy
Benefits
Drug-eluting stents (DES) have been extensively studied, and are generally superior to bare-metal stents concerning the occurrence of
major adverse cardiac events (generally defined as death,
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
, or the need for a repeat
revascularization
In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of rev ...
procedure). In a 2019 meta-analysis comparing new generation DES to BMS, 26,616 patients spanning 20 randomized clinical trials were evaluated for primary outcomes of myocardial infarction and cardiac death. Those who received DES had a significantly reduced risk of myocardial infarction and cardiac mortality at 1 year. The superiority of newer generation polymer stents, particularly the cobalt chromium everolimus-eluting stents have been well-studied.
One of the major benefits of drug-eluting stents (DES) to bare-metal stents (BMS) is the prevention of in-stent restenosis (ISR). Restenosis is a gradual re-narrowing of the stented segment that occurs most commonly between 3–12 months after stent placement. High rates of restenosis associated with BMS prompted the development of DES, which resulted in a reduction of ISR incidence to around 5-10%.
Continued development of newer generation DES have resulted in the near-elimination of BMS from clinical practice.
Long term outcomes
Data on long term effects of DES is limited. This is primarily because the technology has only been around for the last two decades, so many studies investigating long-term outcomes have yet to be concluded. However, there are a number of studies investigating intermediate-term outcomes. One particular meta-analysis looked at 52,158 patients across 51 trials.
At a median 3.8 years follow up, all DES demonstrated superior efficacy compared to BMS, resulting in lower rates of revascularization procedures. Among DES, newer generation devices had substantially improved safety outcomes, specifically in regards to stent thrombosis, recurrent MIs, or death.
In another 2016 trial, 9,013 patients who received either DES or BMS to treat coronary artery disease were followed at 6 years in order to determine differences in rates of all-cause mortality (death from any cause) as well as frequency of repeat revascularization, stent thrombosis, and quality of life measures. At 6 years, there were no significant differences in all-cause mortality or quality of life measures. However, rates of repeat revascularization and stent thrombosis were significantly lower in those who received DES as opposed to BMS.
Adverse effects
Risks
Like all invasive medical procedures, stent placement carries certain risks. Risks associated with
cardiac catheterization
Cardiac catheterization (heart cath) is the insertion of a catheter into a chamber or vessel of the heart. This is done both for diagnostic and interventional purposes.
A common example of cardiac catheterization is coronary catheterization that ...
procedures include bleeding, allergic reaction to the X-ray contrast agents used to visualize the coronary arteries, and myocardial infarction. With PCI, the requirement for emergency CABG has markedly decreased since the days of balloon angioplasty, such that in some communities, coronary stenting is permitted in hospitals without on-site cardiac surgery facilities. This remains controversial in the United States because of the rare but unpredictable risk of coronary artery perforation. Rarely, a type of allergic reaction to the drug may occur; episodes of fatality have been reported.
Stent thrombosis
One of the most feared complications of coronary stenting is stent thrombosis. This occurs when a new clot forms within the stent and occludes blood flow, causing another heart attack.
Treatment for stent thrombosis is emergent revascularization; however, this is only achieved in two thirds of patients. Accordingly, stent thrombosis carries a 30-day mortality risk of 10-25%. The mechanisms responsible for clot formation are multifactorial, including patient factors (smoking, diabetes, hematologic disorders, etc.), choice of stent, and post-procedural factors (duration of antiplatelet therapy, adherence to follow-up).
Although drug-eluting stents continue to represent a major medical advance for angioplasty, there is no evidence to suggest reduced frequency of thrombosis with DES compared to older BMS. What is more, while thrombosis occurs immediately (<24 hours) with BMS, DES have been associated with stent thrombosis up to 3 years after implantation, a phenomenon not seen prior. Explanations may lie in the very nature that these new stents are designed to function. A stent represents a foreign object in the body, and placement of a stent will inevitably lead to damage of a blood vessel's lining (endothelium). Drug-eluting stents, by their nature, prevents the formation of a new endothelial layer. Endothelialization is a hallmark of vascular healing and is important for the prevention of thrombus formation. Without proper healing, the risk of clot formation persists for a much longer period of time.
For drug-eluting stents, the time course of complete healing in humans is unknown.
Thus, clotting suppressant agents are routinely given during placement, and anti-clotting agents are continued well after implantation.
In-stent restenosis (ISR)
As stated earlier, DES were designed to specifically combat issues of restenosis that occurred with BMS. Though less frequent with drug-eluting stents, restenosis still occurs with DES. The process of restenosis is attributable to a phenomenon known as
neointimal hyperplasia. In brief, the process begins with damage to the arterial wall, which can occur in the form of stretch injury during stent positioning or mechanical injury (tearing of vessel lining) during stent deployment. Following injury, platelets, smooth muscle cells, and inflammatory cells (macrophages) will gather at the damaged site and begin the repair process. This can involve the deposition of collagen, proliferation of smooth muscle, and ation of a new vessel lining. However, this process can lead to thickening of the arterial walls and decreased
lumen space, resulting in stenosis.
Since the advent of DES technology, the incidence of ISR has significantly decreased. While rates of ISR ranged from 20-35% with BMS, DES has reduced the incidence to about 5-10%.
This improvement has resulted in the near-elimination of BMS from clinical use; however, research efforts continue on newer generation
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 ...
-based stents, as well as pioneering image-guided stent placement procedures.
Alternatives to stents
Pharmacological therapy for coronary artery disease may be indicated instead of or in addition to invasive treatment. For those requiring
percutaneous coronary intervention
Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the ...
or surgery, medical therapy should be viewed as complementary to revascularization procedures, rather than an opposing strategy.
Coronary artery bypass graft
Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pai ...
surgery is the best treatment for some patients. Differences between outcomes with stenting and with
coronary artery bypass surgery
Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pai ...
(CABG) are a point of controversy. A recent study comparing the outcomes of all patients in
New York state treated with CABG or percutaneous coronary intervention (PCI) demonstrated CABG was superior to PCI with DES in multiple-vessel
coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
. Patients treated with CABG had lower rates of death or myocardial infarction than treatment with a drug-eluting stent. Patients undergoing CABG also had lower rates of repeat revascularization.
Two major randomized controlled trials comparing CABG and DES are either completed or ongoing, and have published results - Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) and Future Revascularization Evaluation in Patients With Diabetes Mellitus—Optimal Management of Multivessel Disease (FREEDOM). The five-year follow-up results of SYNTAX showed, depending on the complexity of coronary vessel disease, PCI was either equally effective or inferior to CABG. Similarly, results from the FREEDOM trial published after five years showed CABG to be superior to PCI in reducing rates of death and myocardial infarction. Both trials found either increased or insignificantly different rates of stroke with CABG as compared to PCI. The registries of the nonrandomized patients screened for these trials may provide as many robust data regarding revascularization outcomes as the randomized analysis.
Other studies, including the ARTS II registry, suggest drug-eluting stenting is not inferior to coronary bypass for the treatment of multiple-vessel coronary disease. The ARTS II registry compared a cohort of patients treated with multiple-vessel stenting with DES, to the historical CABG cohort in the ARTS I trial (itself a randomized comparison between multiple-vessel bare-metal stenting vs. CABG.) At three-year follow-up, major adverse cardiac events were comparable between the ARTS II DES group and the ARTS I CABG group. Reintervention was lower in the ARTS I CABG group.
In all comparison studies of stenting vs. bypass surgery, it is worth noting that only a small minority of patients with multiple-vessel coronary disease have been eligible for inclusion in the studies, and for most patients,
clinical judgement
Medical jurisprudence or legal medicine is the branch of science and medicine involving the study and application of scientific and medical knowledge to legal problems, such as inquests, and in the field of law. As modern medicine is a legal c ...
by experienced operators suggest one or the other approach is preferred.
Design
![Drug-eluting stent](https://upload.wikimedia.org/wikipedia/commons/6/67/Drug-eluting_stent.jpg)
Drug-eluting stents generally consist of three parts - the stent platform, a polymer coating that binds the drug to the stent and releases drug, and the drug.
Stents have been tested that work without the coating layer.
The stent platform itself is an expandable framework, generally with an elaborate mesh-like design to allow expansion, flexibility, and in some cases the ability to make or enlarge side openings for side vessels.
[ The first DES were stainless steel alloys composed of iron, nickel, and chromium and were based on existing bare metal stents.][ These stents were hard to visualize with medical imaging, posed a risk of causing allergic responses, and were difficult to deliver. Subsequent new alloys were used, namely ]cobalt-chrome
Cobalt-chrome or cobalt-chromium (CoCr) is a metal alloy of cobalt and chromium. Cobalt-chrome has a very high specific strength and is commonly used in gas turbines, dental implants, and orthopedic implants. and platinum chrome, with improved performance. Recently, bioresorbable stents
In medicine, a stent is any device which is inserted into a blood vessel or other internal duct to expand it to prevent or alleviate a blockage. Traditionally, such devices are fabricated from metal mesh and remain in the body permanently or unti ...
have been developed in which the stent itself dissolves over time.[ As of 2009, materials that had been explored for use included ]magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
, polylactic acid
Polylactic acid, also known as poly(lactic acid) or polylactide (PLA), is a thermoplastic polyester with backbone formula or , formally obtained by condensation of lactic acid with loss of water (hence its name). It can also be prepared by rin ...
, polycarbonate
Polycarbonates (PC) are a group of thermoplastic polymers containing carbonate groups in their chemical structures. Polycarbonates used in engineering are strong, tough materials, and some grades are optically transparent. They are easily work ...
polymers, and salicylic acid polymers.[ Resorbable stents have held the promise of providing an acute treatment that would eventually allow the vessel to function normally, without leaving a permanent device behind.]
One to three or more layers of polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
can be used in the coating, e.g., a base layer for adhesion, a main layer that holds and elutes (releases) the drug into the arterial wall by contact transfer, and sometimes a top coat to slow down the release of the drug and extend its effect. The first few drug-eluting stents to be licensed used durable coatings. The first generation of coatings appear to have caused immunological reactions at times, and some possibly led to thrombosis. This has driven experimentation and development of new coating approaches.[
The drug is mainly used to inhibit neointimal growth due to the proliferation of smooth muscle cells that would cause restenosis.][ Much of the neointimal hyperplasia seems to be caused by inflammation. Hence, ]immunosuppressive
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
and antiproliferative
Cytostasis (cyto – cell; stasis – stoppage) is the inhibition of cell growth and multiplication. Cytostatic refers to a cellular component or medicine that inhibits cell division.
Cytostasis is an important prerequisite for structured multic ...
drugs are used. 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 ...
, 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 ...
, 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 ...
were previously used for other medical applications and have been included in licensed DES.[
Vascular stents are Class III medical devices that are intended for use as a mechanical radial support to enhance vessel patency over the intended design life of the device. Device properties and the intended use are dependent on results from extensive testing that involve mechanical tests on ]universal testing machine
A universal testing machine (UTM), also known as a universal tester, materials testing machine or materials test frame, is used to test the tensile strength and compressive strength of materials. An earlier name for a tensile testing machine is ...
s. Types of mechanical test include bend testing, fatigue testing
Fatigue testing is a specialised form of mechanical testing that is performed by applying cyclic loading to a ''coupon'' or structure. These tests are used either to generate fatigue life and crack growth data, identify critical locations or de ...
, radial loading, tensile testing
Tensile testing, also known as tension testing, is a fundamental materials science and engineering test in which a sample is subjected to a controlled tension until failure. Properties that are directly measured via a tensile test are ultimate ...
, and torsion testing. Depending on the type of vascular stent, its location and intended use, other tests may include crush resistance, kink resistance, corrosion, coating integrity, and more.
History
The first procedure to treat blocked coronary arteries
The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ of ...
was coronary artery bypass graft
Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pai ...
surgery (CABG), wherein a section of vein or artery from elsewhere in the body is used to bypass the diseased segment of coronary artery. In 1977, Andreas Grüntzig
Andreas Roland Grüntzig (25 June 1939 – 27 October 1985) was a German radiologist and cardiologist, with foundational interest, training and research in epidemiology and angiology. He is known for being the first to develop successful balloon a ...
introduced percutaneous transluminal coronary angioplasty
Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the i ...
(PTCA), also called balloon angioplasty, in which a catheter was introduced through a peripheral artery and a balloon expanded to dilate the narrowed segment of artery. As equipment and techniques improved, the use of PTCA rapidly increased, and by the mid-1980s, PTCA and CABG were being performed at equivalent rates. Balloon angioplasty was generally effective and safe, but restenosis was frequent, occurring in about 30–40% of cases, usually within the first year after dilation. In about 3% of balloon angioplasty cases, failure of the dilation and acute or threatened closure of the coronary artery (often because of dissection) prompted emergency CABGs.
Charles Theodore Dotter
Charles Theodore Dotter (14 June 1920 – 15 February 1985) was a pioneering US vascular radiologist who is credited with developing interventional radiology. Dotter, with his trainee Dr Melvin P. Judkins, described angioplasty in 1964.
Dotte ...
and Melvin Judkins had proposed using prosthetic devices inside arteries in the leg to maintain blood flow after dilation as early as 1964.[ (abstract)] In 1986, Puel and Sigwart implanted the first coronary stent in a human patient. Several trials in the 1990s showed the superiority of stent placement over balloon angioplasty. Restenosis was reduced because the stent acted as a scaffold to hold open the dilated segment of artery. Acute closure of the coronary artery (and the requirement for emergency CABG) was reduced, because the stent repaired dissections of the arterial wall. By 1999, stents were used in 84% of percutaneous {{More citations needed, date=January 2021
In surgery, a percutaneous procedurei.e. Granger et al., 2012 is any medical procedure or method where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using ...
coronary interventions (i.e., those done via a catheter, and not by open-chest surgery).
Early difficulties with coronary stents included a risk of early 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 (thro ...
(clotting) resulting in occlusion of the stent. Coating stainless steel stents with other substances such as platinum or gold did not eliminate this problem. High-pressure balloon expansion of the stent to ensure its full apposition to the arterial wall, combined with drug therapy using aspirin and another inhibitor of platelet
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 ...
aggregation (usually ticlopidine
Ticlopidine, sold under the brand name Ticlid, is a medication used to reduce the risk of thrombotic strokes. It is an antiplatelet drug in the thienopyridine family which is an adenosine diphosphate (ADP) receptor inhibitor. Research initially s ...
or clopidogrel) nearly eliminated this risk of early stent thrombosis.
Though it occurred less frequently than with balloon angioplasty or other techniques, stents nonetheless remained vulnerable to restenosis, caused almost exclusively by neointimal tissue growth. To address this issue, developers of drug-eluting stents used the devices themselves as a tool for delivering medication directly to the arterial wall. While initial efforts were unsuccessful, the release (elution) of drugs with certain specific physicochemical properties from the stent was shown in 2001 to achieve high concentrations of the drug locally, directly at the target lesion, with minimal systemic side effects. As currently used in clinical practice, "drug-eluting" stents refers to metal stents that elute a drug designed to limit the growth of neointimal scar tissue, thus reducing the likelihood of stent 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 ...
.
The first successful trials were of 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 stents. A clinical trial in 2002 led to approval of the sirolimus-eluting Cypher stent in Europe in 2002. After a larger pivotal trial (one designed for the purpose of achieving FDA approval), published in 2003, the device received FDA approval and was released in the U.S. in 2003. Soon thereafter, a series of trials of 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 ...
-eluting stents led to FDA approval of the Taxus stent in 2004. Both 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 ...
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 ...
are natural products
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical sy ...
, making the drug-eluting stents a specific kind of application totally dominated by drugs directly derived from natural sources.
The first resorbable stent tested in humans was developed by the Igaki Medical Planning Company in Japan and was constructed from poly-L-lactic acid (a form of polylactic acid
Polylactic acid, also known as poly(lactic acid) or polylactide (PLA), is a thermoplastic polyester with backbone formula or , formally obtained by condensation of lactic acid with loss of water (hence its name). It can also be prepared by rin ...
); they published their initial results in 2000. The German company Biotronik
Biotronik (BIOTRONIK SE & Co. KG; Biotronik Worldwide) is a limited partnership multi-national cardiovascular biomedical research and technology company, headquartered in Berlin, Germany.
The company offers equipment for diagnosis, treatment, ...
developed a magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
absorbable stent and published clinical results in 2007.[ The first company to bring a bioresorbable stent to market was Abbott Vascular which received a European marketing approval in September 2012; the second was Elixir which received its CE mark in May 2013.][
In 2017, Abbott pulled its bioabsorbable stent, Absorb, from the European market after negative press regarding the device. ]Boston Scientific
Boston Scientific Corporation ("BSC"), incorporated in Delaware, is a biomedical/biotechnology engineering firm and multinational manufacturer of medical devices used in interventional medical specialties, including interventional radiology, in ...
also announced termination of its Renuvia bioresorbable coronary stent program as studies showed higher risk of serious adverse events.
Due to challenges in developing resorbable stents, many manufacturers have focused efforts on targeting or reducing drug-release through bioabsorbable-polymer coatings. Boston Scientific's Synergy bioabsorbable polymer stent has been shown potential to reduce length of dual antiplatelet therapy post-implantation. MicroPort's Firehawk target eluting stent has been shown to be non-inferior to traditional drug-eluting stents while using one-third of the amount of equivalent drug.
Society and culture
In 2012, a meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
of clinical trial data was published, showing that, for people with stable coronary artery disease, DES has no benefit compared to treatment with drugs. ''The New York Times'' interviewed the study's main author, who said that more than half of patients with stable coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
were implanted with stents without even trying drug treatment and that he believed this happened because hospitals and doctors wanted to make more money. In 2013 the Times of India reported that DES were widely overused and that Indian distributors used profits from high markups on DES to bribe doctors to use them. In 2014 an investigation by the Maharashtra
Maharashtra (; , abbr. MH or Maha) is a states and union territories of India, state in the western India, western peninsular region of India occupying a substantial portion of the Deccan Plateau. Maharashtra is the List of states and union te ...
Food and Drug Administration found that high markups and bribery related to DES was still widespread.[Rema Nagarajan for the Times of India. Sep 15, 201]
Profits from medical devices used to bribe doctors?
/ref>
References
Further reading
* (layperson overview, subscription required)
* (journal review article, subscription required)
External links
Drug-Eluting Stents — Angioplasty.Org
Good overview and detail
CIMIT Center For Integration of Medicine and Innovative Technology
Cypher DES
Image of the experimental CoStar Cobalt chrome stent
* ttp://www.medpagetoday.com/MeetingCoverage/TCT/ TCT: Transcatheter Cardiovascular Therapeutics Meeting Coveragepeer-reviewed articles from Medpage Today
MedPage Today is a medical news-focused site owned by Ziff-Davis, LLC. It is based in New York City, and is geared primarily toward medical and health professionals.
History
The news service MedPage Today was founded by Robert S. Stern in Marc ...
{{DEFAULTSORT:Drug-Eluting Stent
Drug delivery devices
Implants (medicine)
Interventional cardiology