With cardiovascular disease still the most common cause of death in industrialised countries, endovascular devices have proven to be effective alternatives to certain open-heart surgeries. Over the last 20 years, intra-coronary stents have replaced many bypass operations as the first line treatment for patients with chronic coronary artery disease and, lately, have also become first line treatments for acute myocardial infarction.
Bare metal and drug-eluting stents have become the most commonly prescribed de-facto standard therapy, but there still remain challenging cases in which these devices are not ideal for particular subsets of patients undergoing coronary angioplasty. Advances in the biomechanics of stent design have provided interventional cardiologists with new tools for treating patients where drug-eluting stents are potentially contraindicated, while continuing to offer them a less invasive alternative to conventional bypass surgery.
New stents combine modern stent structural design technology with endothelial progenitor cell (EPC) capture technology to accelerate the natural healing of the vessel wall after the implantation of the blood contact device.
The antibody surface coating of the device captures EPCs circulating in the blood and accelerates the formation of an endothelial layer that offers protection against thrombosis (clotting) and restenosis (the re-narrowing of the artery).
This biomechanical approach not only speeds the healing of coronary artery walls unavoidably injured after the placement of a device, but it also reduces the time that patients are required to undergo the necessary anti-thrombotic drug therapy prescribed after the intervention.
Dual antiplatelet therapy (DAPT), a blood thinning drug treatment, while essential to prevent acute thrombosis of a newly implanted stent, poses risks for patients with blood disorders or even those who must undergo near-term future surgical operations. For these patients stents equipped with EPC technology offer the benefit of a shorter DAPT requirement, improving outcomes and reducing patient risk. No single stent is perfect for every patient, and with new options for treating coronary artery lesions, interventional cardiologists are able to treat patients undergoing angioplasty with high efficacy and lower risk.
Stents: a short history
The last 20 years of stent evolution have seen a generational advance on previous technology and, from these advances, the majority of current intracoronary treatments have been based. In the late-1970s patients with coronary artery disease were able to avoid bypass surgery where needed after the first implementation of simple balloon angioplasty as a new technology.
In the early days of this treatment, there was a 20-50% rate of vessel restenosis, and this led to the standard of care that combined angioplasty and the then newly conceived stents. The first bare metal stents reduced the rate of restenosis to approximately 15-25%, and, with time and improvements, this complication has been reduced to under 5-10%, with the emergence of the latest drug-eluting stents.
Drug-eluting stents combat restenosis by releasing chemical agents to prevent smooth muscle cell proliferation. With any foreign object introduced into the human body comes the risk of adverse events. Conventionally, patients are required to undergo DAPT for a standard duration of up to one year to avoid thrombosis at the site of implantation - thrombosis either immediately following stent surgery, late thrombosis (occurring 30 days to one year, post-stent placement), or very late thrombosis (occurring over one year post-stent placement.
In terms of drug-eluting stent advances there have been great improvements in the polymers used in manufacturing. Current stents are the least inflammatory and the most inert biologically on a historical basis. Endothelialisation of the stent over time ultimately reduces the risks of stent thrombosis and the extreme complications related to it, including myocardial infarction and death. Until this endothelialisation process is complete DAPT is seen as a necessary practice.
Late and very late stent thrombosis occurring years after stent placement may be explained in part by incomplete stent endothelialisation. Any technology that promotes healing and endothelialisation therefore, not only reduces time on blood-thinning medication, but should also protect against late and very late thrombosis.
Patients where dual antiplatelet therapy is contraindicated. A patient subset requiring particular attention is those patients in whom, for whatever reason, DAPT is contraindicated. The widely accepted one-year duration of a standard DAPT prescription can be problematic for some, for example, one group of such individuals who require another (non-cardiac) surgery within one year of cardiac stent placement. A year prescription of DAPT, for the prevention of late or very late thrombosis, increases bleeding risk of the additional but necessary operations, making a difficult treatment choice for both patient and doctor.
Alternately, a patient with an active non-cardiac bleeding risk, such as a gastric ulcer or lower GI bleed, may require urgent intracoronary stenting clinically, while being at excess bleeding risk again from the necessary DAPT.
Acute myocardial infarction. 40% of patients requiring stent placement have acute coronary syndrome (ACS), and of these, 15% have AMI. Suffering an ACS is an extremely pro-thrombotic state and concern has existed in treating AMI patients with drug-eluting stents particularly because of an observed potential excess risk of acute stent thrombosis.
Drug-eluting stents are designed to prevent restenosis specifically, and are deemed by many cardiologists to be a better choice in the long-term, especially in patients at high vascular risk (for example, diabetics).
The choice of stent, therefore, in ACS patients is often weighed by the perceived risk of short-term stent thrombosis versus long-term restenosis and, although the concern about drug-eluting stents-related stent thrombosis has lessened in the last couple of years, doctors often may still opt for the bare metal stent in this setting for fear of provoking a stent thrombosis complication.
Disorders of the blood. There are the obvious issues of putting a patient with a high risk for bleeding on DAPT, but consider a patient who has a hyper-coagulable blood and presenting with thrombophilia (a form of hypercoagulability), a condition that leads to an excess production of platelets, and, as a result, the risk of premature, excessive and troublesome blood clotting in their organs.
In such a patient, the implantation of any metallic object in their circulation will generally risk significant thrombosis related to the object. For example, with a stent in a coronary artery in a patient with thrombophilia there would need to be very aggressive antiplatelet and anticoagulant therapy to try and prevent stent thrombosis from occurring.
In this situation these adjunctive therapies would be appropriately prescribed, but this could lead to issues of reduced patient compliance and reduced patient tolerability of high dose drugs on a long-term basis.
In all the above clinical settings, a stent device that offers a reduced period of DAPT and/or promotes earlier stent endothelialisation would be the obvious treatment advantage.
Genous Bio-engineered R stent
The Genous™ Bio-engineered R stent™, developed by OrbusNeich, takes advantage of EPC capture technology to accelerate healing of the arterial wall and thus shortens the duration of dual antiplatelet therapy and prevents late and very late thrombosis complications. For interventional cardiology, the Genous stent offers a compelling alternative to bare metal and drug-eluting stents for patients presenting with the challenges described above.
Genous Bio-engineered R stents maintain the traditional scaffold structure for the modulation of restenosis, but they are uniquely coated with immobilised anti-CD-34 antibodies.
These antibodies capture the EPCs by binding to them as they circulate in the bloodstream to accelerate the formation of a functional endothelial layer.
From a thrombosis viewpoint, one of the driving forces that initiates the blood clot formation is the exposition of bare metal or polymer on the drug eluting stent platform to thrombogenic factors in the circulating blood. By accelerating endothelialisation, Genous Bio-engineered R stents, therefore, potentially reduce the duration of such thrombogenic exposure.
Improved clinical outcomes for challenging cases
In over 5,000 patients worldwide the novel biomechanics of a stent using EPC capture technology has been proven in research trial data to treat patients as effectively as its non-EPC counterparts while offering accelerated healing, a decreased duration of blood thinning drug therapy and the prevention of thrombosis even years after angioplasty.
A recent study of patients who needed coronary revascularisation, and were already scheduled for a non-related surgery, receiving only around 12 days dual antiplatelet therapy in combination with the Genous Bio-engineered R stent, demonstrated that this innovative technology is a good alternative for this particular patient subset, in preventing stent implantation related thrombosis complications despite a much shortened DAPT regime.
The second situation in which Genous is a good choice is that of a pro-thrombotic state or an obvious large thrombus burden in the coronary artery at the time of stent implantation.
Patients suffering from myocardial infarction are often in the situation as described above where much thrombus and plaque within their coronary arteries mandate an angioplasty treatment as an urgency. Urgent angioplasty is the first line optimum treatment for such acute myocardial infarction where advanced thrombolysis is the more conventional, and now slightly passé, treatment.
In these patients the Genous Bio-engineered R stent can take advantage of the fact that AMI patients manifest elevated EPCs due to the injury as the body begins naturally to heal itself. The Genous Bio-engineered R stent captures the functional EPCs in circulation to immediately aid in this process.
Clinical data has demonstrated the Genous Bio-engineered R stent's safety profile in patients presenting AMI. In cases where there is much thrombus within coronary circulation, aggressive antiplatelet and anti-thrombotic drug treatment is always employed, but the advantage of a stent platform that decreases the immediate risk of stent thrombosis is an additional advantage.
There are clinical focus points where the Genous Bio-engineered R stent is settling into a niche and where it certainly maintains a logical and scientific advantage. In addition, evidence is accumulating of significant patient outcome advantage with reduced stent-thrombus related complications. These advantages exist in cases where the challenge relates to the hazards of prolonged dual anti platelet pharmacology or the cases where the benefits of earlier stent endothelialisation reduce thrombosis as a clinical outcome.