An overview of coronary stents evolution, its current status and future directions.
The heart has a network of coronary arteries which circulates blood within the organ. From the aorta, vessels branch off to form the right and the left coronary arteries for coronary circulation. Coronary artery disease is the obstruction of any of these vessels, resulting in heart attacks or acute coronary syndrome.
Coronary artery disease (CAD), either narrowing (stenosis) or blockage (occlusion), arises from plaque deposition in the arterial wall, also known as atherosclerosis. This results in restriction of blood flow and hence oxygen to the heart muscle, which is called ischemia. Atherosclerosis is beyond just the accumulation of lipids, as it also a series of responses characteristic to inflammatory disease. CAD could be chronic (arteries narrowing over time) or acute (sudden rupture of plaque), both of which require stent-based coronary intervention, to relieve the arteries of the obstruction and regulate normal blood flow to the affected cardiac muscle.
Percutaneous coronary intervention (PCI) was introduced in the late 1970s by Dr. Andreas Gruentzig and that has revolutionized the management of stable and unstable coronary artery disease. Before that, coronary artery bypass grafting surgery was the only option of treatment besides medications. PCI offers an effective, safe and readily available method for coronary revascularization for many patients. Over the past four decades, this specialty has witnessed rapid development which eventually led to the introduction of a number of new technologies, including coronary stents that have resulted in improved efficacy and long-term safety. These technologies include new generations of drug-eluting stents, non-polymeric stents, bioresorbable polymer-coated stents, and fully bioresorbable scaffolds.
Evolution of Stents
Current generation stents that provide remarkable results owe their origin to their earlier versions, which were rudimentary in design. Coronary angioplasty, conceptually described by Dotter and Judkins in 1964, was first performed by Andreas Gruntzig in 1977. Coronary stents were developed in the mid-1980s and since then have seen major refinements in design and composition. The landmark events in the evolution of stents are shown in Table 1.
Table 1: Evolution milestones in coronary artery stenting
|1964||Dotter and Judkins conceptual description of coronary angioplasty using an implantable prosthetic device|
|May 1977||Gruntzig conducts first coronary angioplasty|
|September 1977||Andreas Gruntzig conducts first coronary angioplasty in an awake patient; a revolution in interventional cardiology|
|1979||Geoffrey Hartzler does first balloon angioplasty to treat AMI|
|1986||Sigwart and Puel perform the first implantation of a stent in human coronary arteries; the second revolution in interventional cardiology|
|1994||FDA approves the use of for heart patients|
|1999||Eduardo Sousa uses the first drug (sirolimus) eluting stent implanted in the human coronary artery; third revolution in interventional cardiology|
|2011||FDA approves bio-absorbable stents; the fourth revolution in interventional cardiology|
FDA, Food and Drug Administration USA
Types of Stents
|Bare Metal||The first stents were made of metal, mostly steel. But these caused arteries to shrink back in a few months, defeating the purpose. The shrinkage occurred due to the presence of a foreign metal body.|
|Second Generation DES||Better polymers were used to manufacture drug-eluting stents. These stents substantially reduced the risk of onset of late thrombosis of blood clotting at the site of the stent and also helps in better tissue healing.|
|Bio-absorbable Polymer DES||These are DES that has a polymer coating that can dissolve after a few months. Thus, they provide the advantage of DES in the first few months and later become bare metal stents with reduced risk of clotting.|
|Bioresorbable||This next generation will continue to dominate research for years to come. The entire stent is reabsorbed and eventually disappears.|
|Drug Eluting Stent (DES)||This triggered a revolution in stent manufacturing. Realising the limitations of bare metal stents, companies started to coat the metal with drugs. After a while, patients with implanted DES developed late state thrombosis, which means sudden blood clot at the site of the stent after a year or two of the procedure.|
Initially, balloon angioplasty was first introduced as a less invasive alternative to coronary artery bypass grafting surgery. However, the major setback of balloon angioplasty was the high rate of acute arterial closure due to recoil and dissection, which resulted in myocardial infarction. The introduction of coronary stents in the 1990s has drastically reduced the incidence of acute arterial closure and ever since stent implantation became the standard of care percutaneously.
A stent is a tiny mesh tube that is designed to remain permanently implanted at the intended vessel. Briefly, a guide-wire is advanced across the diseased segment of the artery. Then, a balloon catheter is positioned to compress the plaque against the arterial wall, and then a stent is deployed to provide permanent mechanical support, thus preventing acute arterial closure.
First generation stents were made of bare metal (stents without medication), which had an in-stent restenosis rate of 20-30%. Arterial re-narrowing within the area of stent implantation (in-stent restenosis) occurs due to a process called neo-intimal proliferation. As a solution to this problem, drug-eluting stents (DES) was designed in 1999. DES are coated with medication to disrupt the process of restenosis and hence effectively reduced the rate of restenosis to less than 10%. However, DES also unexpectedly increased the risk of stent thrombosis, a life-threatening complication. There are a number of reasons why stent thrombosis can occur, namely delayed endothelialisation of stent struts, hypersensitivity to drugs or polymer coating of the stent or stent mal-apposition. To prevent this from happening, prolonged dual-antiplatelet therapy is mandatory following DES implantation, but at a slightly increased risk of bleeding. The various problems encountered have been the constant impetus for innovation in coronary stent designs and technology which ultimate aim was to improve clinical outcome.
Early coronary stents were made of stainless steel that has relatively large stent struts. As such, their flexibility is limited and resulted in higher restenosis rate. Newer generation stents have largely replaced stainless steel with cobalt alloys. This enabled longer stents with thinner struts to be developed and these have provided more flexibility to achieve better vessel conformability, without compromising its radial strength.
Additionally, new DES technologies comprise novel polymeric materials, for controlled release of medication at the implanted site. Since polymer coatings are redundant after drug release, newer generation DES are therefore made up of biocompatible or biodegradable polymer coatings that dissolve after drug release is completed. Further development has explored an approach that removes the polymer coating entirely, hence forming a polymer-free DES which releases medication directly from the stent surface. All these have made possible a shorter duration dual-antiplatelet therapy, which eventually translates to lower bleeding risk.
The current trend is seeking to replace a permanent metallic prosthesis with something which will completely disintegrate or disappear once its supporting purpose is fulfilled. This results in what is known as a bioresorbable scaffold. The potential advantages of having the stent disappear include reduced risk of late stent thrombosis, future vessel assessment with computed tomography and restoration of normal arterial motion. However, the setbacks include bulky stent struts that are less deliverable, stent fracture due to aggressive balloon dilatation and lack of radio-opacity. Hence, a lot of research and development in this area is ongoing as the existing bioresorbable scaffolds are still far from perfect.
DidYouKNow>>>> Most bioresorbable stents are made of polylactic acid, a naturally dissolvable material that is used in medical implants such as dissolving sutures.
The field of PCI is evolving to facilitate safe and optimized treatment for patients with coronary artery disease. Stent technologies will continue to focus on the above issues to create even better stents. Although the ideal stent is still nowhere in sight, most contemporary stents are reasonably safe and effective options, providing low incidence of stent complications.