Final Blog

We hope that this blog has allowed you to follow the development of percutaneous coronary intervention, which began in 1977 when Andreas Gruntzig first introduced balloon angioplasty and which has progressed to second/third-generation drug eluting stents and biodegradable stents. By looking at this path, one can appreciate the many difficulties researchers have faced trying to treat obstructive coronary artery disease., Yet, it is encouraging that recent technological gains with coronary stents do appear to prevent restenosis of the artery while limiting serious side effects.

On multiple occasions, this blog has shown when one problem is solved by a new technology, unfortunately another one seems to be created. Balloon angioplasty was first developed for the management of coronary stenosis. Even though this was a major breakthrough, it had two major drawbacks, a high risk of immediate dissection of the artery followed by a risk of restenosis occurring later in a little over one half of the patients. To solve the problem of immediate dissection, balloon expandable bare metal stents were developed in 1987 to provide support to the artery. Restenosis also showed reduction with bare metal stents, with the risk of restenosis around 30% in patients. In the early 21^st century, drug-eluting eluting stents were designed to inhibit restenosis by releasing pharmacological agents (typically anti-proliferative compounds which induced cell cycle arrest in G1 phase) to block vascular smooth muscle cell proliferation. Many of the articles reviewed in this blog have shown that these drug eluting stents have been able to prevent neointimal hyperplasia and arterial remodeling, which are the two main processes that lead to restenosis. Restenosis rates had dropped to below 10% in patients who had received a drug-eluting stent.

Although drug-eluting stents proved to reduce restenosis, long term followup studies began to suggest that they might be associated with a higher risk for stent thrombosis as compared with bare metal stents. Some of the drugs used in the stents such as rapamycin and paclitaxel have been shown to induce the expression of tissue factor, an important part of the initiation of coagulation and thrombus formation. Also, the polymers used to hold and release the antiproliferative drugs occasionally caused local allergic reaction resulting in chronic inflammation which predisposed to thrombosis.

The current health care debate, therefore, is whether these drug-eluting stents are more advantageous than bare metal stents or if the risk of thrombosis is too high and do not outweigh the benefits. At this point, it is our opinion that drug-eluting stents do provide more benefit than risk and it is a sustainable technology. However the thrombosis risk deserves continued close surveillance. It is also recommended that patients who receive drug-eluting stents take aspirin and Plavix for at least a year after the procedure to lessen the chance of clotting. Still, it is the hope that future coronary stents will be further improved so that these deleterious side effects will be eliminated and that the duration of dual antiplatelet agents, were there incumbent risk of serious bleeding, can be limited.

For the future, when developing new drug-eluting stents, researchers need to attempt to develop stents that can eliminate or have a significantly reduced incidence of restenosis. Researchers should also concentrate on developing stent materials/ polymers that do not cause hypersensitivity reactions and simultaneously reduce the risk of thrombosis. Multiple technologies, including novel antiproliferative agents, polymers, and stent designs, are currently being researched and designed to be used in second and third generation stents. For example, the SPIRIT trial investigated the use of a newer ‘limus’, everolimus, believed to be a more effective antiproliferative agent, embedded on a less toxic polymer matrix, mounted on a thinner strut, more maneuverable stent. Also, bioabsorbable stents have been gaining a lot of interest. They are thought to represent an alternative revascularization modality that would address the short-term need for a vessel scaffolding but avoid the complications of thrombosis and inflammation seen when a foreign body is left within a vessel. The bioabsorbable magnesium stents are promising in that magnesium is expect to have beneficial effects by acting as a systemic and coronary vasodilator. Initial results of the Absorbable Metal Stent (AMS) from Biotronik have been favorable. This stent appears to reduce intimal proliferation, to have no stent-related adverse effects, and to have no prothrombotic effects. Although these new technologies appear very promising, more and larger clinical studies are needed before they can be viable options for patients with coronary artery disease. We have learned our lesson with the (too)rapid acceptance of DES technology- new technologies often bring new, unexpected problems that can not be identified in initial, small patient trials.

Although much controversy has surrounded drug-eluting stents, we believe that they are currently the best viable for the percutaneous treatment of obstructive coronary artery disease. As for the immediate future, second and third generation stents appear to continue to lower restenosis rates while reducing potentially dangerous side effects. But stent polymer and drug technology will continue to progress exponentially. In the future, we expect that we will have multiple different stents allowing us to tailor the stent and the drug to the patient's disease state. For instance, diabetics may require a more potent antiproliferative than non diabetics. Older, more debilitated patients with a higher risk of bleeding and an inability to take dual antiplatelets will need a stent with less thrombosis potential. The future is always difficult to predict but it is quite apparent is that our third generation stents are not the end, rather they are just the beginning in the evolution of a very promising technology.

Blog #12

Steffel, Eberli et. Al. “Drug-eluting stents-what should be improved?” Annals of Medicine. 2008; 40: 242-252

http://informahealthcare.com/doi/full/10.1080/07853890801964948

As we have seen in prior papers, although drug-eluting stents provide multiple benefits including reduced restenosis and the need for target vessel revascularization, there is also a tradeoff with a risk of stent thrombosis. The risk continues to grow after cessation of dual antiplatelet therapy, with a high morbidity and mortality, and the numbers imply that there is a higher risk in ‘real-world’ patients.

In this paper, Steffel et al. look at the problems inherent to the current generation of drug eluting stents and how they can/are being improved in second and third generation stents. Early in their paper they label three aspects of current available drug-eluting stents that need improvement: 1) Further reduction in restenosis, especially after stenting of complex lesion, 2) Avoidance of unwanted effects due to the stent polymer, and 3) reduction of the risk of stent thrombosis. With these three guidelines set out, the authors search through the different recent technological advances that are currently under investigation. In particular they examine novel antiproliferative agents, polymers, and stent designs. Some novel drugs that are currently under investigation include rapamycin analogues like zotarolimus, which is currently being used in the second generation stent Endeavor. In terms of novel polymers, researchers are trying to create polymers that could both be biocompatible and bioabsorbable. These are considered important goals in order to create a stent that can expedite re-endothelialization and limit stent thrombosis, thereby minimizing the duration of DAPT. Other aspects researchers have looked into are reservoir stents (different drug can be loaded on the luminal and adluminal (outside surface against the wall) side of the stent, coating with pro-endothelial agents (in order to enhance endothelial healing thereby reducing thrombogenicity of the stent), and coating with other anti-restenotic agents (to try to completely knock off restenosis).

Although there are many innovative novel principles that seem appealing and have demonstrated good results in initial clinical evaluation, many of these have been performed in a small number of highly selected patients and not in a large scale study. Therefore these newer therapies need further and deeper investigation before their place can be determined in Interventional Cardiology. As of now, the ideal stent appears to be one with the elution of an anti-restenotic agent with a ‘pro-healing’ (bioabsorbable/biocompatible) platform to enhance re-endothelialization. It is also hoped that one day there will different stent types for specific clinical situations. Finally there is a need for these future stents to possess potent anti-inflammatory and potent antithrombotic properties. This article shows that the future of drug eluting stents looks promising but it is still very much a young and evolving field. The ideal DES is still a ways off with many large clinical trials necessary to define it’s efficacy and potentially new limitations.

Blog #11

Stone, G. W. et al. “Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial.” Epubmed February 10 (2009): 119(5): 680-6.

http://www.ncbi.nlm.nih.gov/pubmed/19171853?ordinalpos=&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.SmartSearch&log$=citationsensor

Nikolosky E, et al. “SPIRIT IV trial design: a large-scale randomized comparison of everolimus-eluting stents and paclitazel-eluting stents in patients with coronary artery disease.” American Heart Journal. October 2009: 520-526.

http://www.ncbi.nlm.nih.gov/pubmed/19781409?ordinalpos=&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.SmartSearch&log$=citationsensor

As our understanding and usage of drug-eluting stents continues to improve and advance, better treatments for coronary artery lesions are surfacing. In a recent (2009) randomized comparison in the treatment of patients with de novo native coronary artery lesions known as the SPIRIT III trial, it was found that everolimus-eluting stents show better results than paclitaxel-eluting stents. Paclitaxel-eluting stents (PES) are currently widely used, but one could safely say that these will soon be replaced by everolimus-eluting stents (EES). Paclitaxel is a mitotic inhibitor used in cancer therapy, whereas everolimus, like sirolimus and zotolimus, works as an mTOR (mammalian target of rapamycin) inhibitor and is used as an immunosuppressant to prevent rejection of organ transplants. The comparison study found that patients treated with EES experienced statistically significant reduction in angiographic in-segment late loss at eight months, a surrogate marker for restenosis, and noninferior rates of target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 1 year. Additionally, these patients experienced significantly improved event-free survival at a 2-year follow-up in the SPIRIT III trial. Although further study is needed, the trends show that EES-treated patients are experiencing fewer stent thrombosis episodes after six months than PES-treated patients.

In a follow-up article on the comparison of EES and PES in the SPIRIT III trial, researchers argue that the trial was not powered for superiority for clinical end points and the routine performance of angiographic follow-up may have artificially exaggerated the absolute benefits of EES. Therefore, an additional SPIRIT IV trial is currently underway to find more conclusive evidence on the subject. This trial is a prospective, active-controlled, single-blinded, multicenter clinical trial with 3690 patients with native coronary artery disease. We already assume that EES is superior to PES, but we should not base our knowledge on under supported evidence. Due to its size and controls, the results of this study will more aptly determine the efficacy and side effects of everolimus and paclitaxel-eluting stents and further define their clinical utilities.

Blog #10

Fajadet, Jean at el. Circulation: Journal of the American Heart Association. “Randomized, Double-Blind, Multicenter Study of the Endeavor Zotarolimus-Eluting Phosphorylcholine-Encapsulated Stent for Treatment of Native Coronary Artery Lesions” Aug 14, 2006

<http://circ.ahajournals.org/cgi/reprint/114/8/798>

Like previous postings, this article further examines different types of stents by trying to solve the continuous problems of thrombosis and restenosis following the stenting procedure. This particular study, published in Circulation in August of 2006, examines the Endeavour Zotarolimus eluting stent. Precious posts examined studies with drugs such as paclitaxel and sirolimus eluting stents while this one examines zotarolimus. This clinical study, like the others, compares a drug eluting stent to the bare metal stent. However, this study was more comprehensive in the sense that there were 1,200 patients involved (about 600 with the bare metal stent and 600 with the drug eluting stent).

The study found that there were significant differences between bare metal stents and this new drug eluting stent. For example, within 9 months, there was 15.1% vessel failure in the bare metal stents compared to the 7.9% with the zotarolimus eluting stent. Similarly, there was a 14.4% major cardiac event occurrence with the bare metal compared to 7.3% with the drug eluting stent. In addition, there was 0.5% thrombosis, or clotting with the drug eluting stent compared to 1.2% with the bare metal stent.

We already knew that there are some major benefits to the drug eluting stents, but the controversies are centered on the instances of thrombosis and restenosis following the procedure, and if the drug eluting stents have significantly different rates compared to the bare metal stents. This study seems to further confirm the benefits of 2^nd genration drug eluting stents and supports the evidence to use drug-eluting stents as a part of current health care. This study, in particular, provides stronger evidence because of the length of the study, as well as the number of patients involved. The debate still remains whether the efficacy of drug eluting stents outweighs the inherent safety risks. The only way to further study the efficacy versus safety debate is to increase the pool of patients involved and to study the effects over an even longer period of time. We also need to define the specific issues with drug eluting stents and how they can be remedied for the newer generations of drug eluting stents.

Blog #9

Shuchman. “Trading Restenosis for Thrombosis? New Questions about Drug-Eluting Stents”. The New England Journal of Medicine. 355. November 9 (2006): 1949-1952. Print

http://nejm.highwire.org/cgi/content/extract/355/19/1949

Up to this point, drug-eluting stents have had a golden reputation. They had proven to be able to reduce both emergency cardiac surgery and additional angioplasty. They are also associated with substantially lower restenosis rates than bare metal stents as proven by prior papers. At the time of this paper (2006), more than 90% of angioplasty procedures used drug-eluting stents rather than bare metal stents and more than 6 million patients have drug eluting stents in their arteries

However, in this editorial Shuchman reviews the growing concerns with drug-eluting stents: late thrombosis. “Late stent thrombosis (LST)” is defined as occuring 3 to 6 months after the surgery, while “very late stenosis thrombosis (VLST)” is greater than 6 months. After tracking patients from early clinical trials researchers have discovered that thrombosis is a major concern. For example, four years of data on nearly 3500 patients randomly assigned to receive a drug eluting stent (Taxus) or a bare metal stent has shown the risk of thrombosis formation 6 months after Taxus stent placement. The difference in risk increased by .2% per year, so 3 years after stent placement there is a .5% higher risk in Taxus over the bare metal stent. These reviewers suggested that there might be an increased risk of myocardial infarction and death associated with stent thrombosis.

What does this mean for the public? Well at the time of this article the FDA claimed that there is a “small additional risk of late stent thrombosis after a year”. Is this risk worth it? The newer drug eluting stents do confer better protection against restenosis but do have this small thrombosis risk. Therefore, many physicians now concluded that an extended or lifetime prescription of aspirin and plavix (clodigrel) are necessary when a patient receives a drug eluting stent. The initial recommendation of 6 months was extended to “12 months or indefinitely”, unless a patient has a high risk of bleeding. These stents are thus still beneficial and useful but second and third generation drug eluting stents should look into creating better polymers to solve this thrombosis problem.

Blog #8

Stone, Gregg W et al. The New England Journal of Medicine “Safety and Efficacy of Sirolimus- and Paclitaxel-Eluting Coronary Stents” March 8, 2007

http://content.nejm.org/cgi/content/full/356/10/998

This clinical study was published in the New England Journal of Medicine in 2007. At this time, it was evident that while drug-eluting stents could effectively prevent restenosis, but their implantation might present a new more serious health risk—stent thrombosis. Previous studies, such as the trial discussed in the previous blog, suggested that a previously unrecognized deleterious side effects from implantation of drug-eluting stents might be stent thrombosis resulting in heart attacks, and even death.

This study compares not only the safety and efficacy of drug-eluting stents to bare-metal stents, but also compares two different drugs, Sirolimus- and Paclitaxel. The study traces rates of stent thrombosis and target-lesion revascularization, defined as the need to perform multiple percutaneous interventions, or bypass, at the target site. This article suggests that both sirolimus and paclitaxel-eluting stents are more likely to induce stent thrombosis than bare-metal stents. But, it also shows that the drug-eluting stents greatly reduce the need for more surgeries to combat restenosis. No marked difference was observed between the two different drug-eluting stents. Similarly, there was no difference in heart attack or death rates between the bare-metal and drug-eluting stents.

This article obviously reinforced physician and public confidence in the ability of drug-eluting stents to reduce restenosis rates, and thus reduce the need for a patient to undergo the trauma and cost of multiple surgeries. But, the study does not do much to alleviate concerns about the safety of drug-eluting stents. While it shows that death and heart attack rates do not rise with the use of drug-eluting compared to that of bare-metal stents, it suggests that these new, drug-eluting stents produce higher rates of stent thrombosis than older, bare-metal stents when dual antiplatelet therapy(DAPT) is continued beyond 6 months. This study encourages researchers to pursue drug-eluting stents that eliminate, or at least lower, the risk of stent thrombosis and to reexamine the duration of DAPT.

Blog #7

Schofer, Schluter, Gershlick et al. “Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomized controlled trial.” Lancet. 362. October 2 (2003): 1093-1099. Print.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1B-49NV339-7&_user=489286&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1121247921&_rerunOrigin=scholar.google&_acct=C000022678&_version=1&_urlVersion=0&_userid=489286&md5=3c4c00a33c12270374d606039ea7a222

This article from Lancet provides more information about the Sirolimus-eluting stent. The previous article proves that Sirolimus-elutin stents are more effective than a bare metal-stents in preventing neointimal hyperplasia. This study helps confirm this belief.

Schofer and his colleagues in Germany went further in depth and examined patients with higher risk profiles for restenosis. This higher risk group included patients with previous myocardial infarction (42%) and current smokers (33%). They often tended to have small mean reference vessel diameter and long average lesion length, both of which predispose to restenosis. 352 patients were enrolled in this study, with vessel diameters ranging from 2.5-3 mm and lesion length from 15-32 mm. Two groups were compared, a sirolimus-eluting stent group (n=175) and a bare-metal stent group (control, n=177). The researchers examined the difference in lumen diameter after 8 months and whether patients had major adverse cardiac events at 9 months. It was a double blind study and randomized to allow for an effective examination of the two groups.

This trial concluded that sirolimus-eluting stents are more effective than the typical bare-metal stent. After 8 months, the control group had a significantly higher lumen diameter than the sirolimus-eluting group (2.22 vs 1.33). The sirolimus-eluting group also had significantly lower adverse cardiac events (8% vs 22.6%) and a lower need for target-lesion revascularizations. This study shows that for every 1000 patients undergoing stent implantation, with sirolimus-eluting stents, about 170 will be spared a repeat procedure.

This article presents sirolimus-eluting stents as an effective, new technique to reduce restenosis and the need for future procedures. However, this paper also presented a pressing health risk associated with the use of drug-eluting stents—stent thrombosis. In this study, there were two subacute stent thromboses (formation of blood clots in the vessel which could lead to future heart attacks) in sirolimus-stent patients, but none in the control. While researchers claimed that the frequency of stent thromboses between the study groups was “far from significant and might thus be due to chance,” this study for the first time raised the alarm and suggested that potentially catastrophic stent thrombosis from drug-eluting stents might be real problem which thus must be further studied.

Blog #6

Jeffrey W. Moses, M.D. et al. "Sirolimus-Eluting Stents versus Standard Stents in Patients with Stenosis in a Native Coronary Artery." New England Journal of Medicine. 349. (2003): 1315-23.

http://content.nejm.org/cgi/content/full/349/14/1315

As has been previously discussed, the clinical usefulness of coronary stents in percutaneous revascularization is undeniable. They have proven to be more effective than balloon angioplasties due to procedural safety and reduced rates of restenosis. This study confirms what was found in the previous post with regards to the use of drug-eluting stents as a solution to the problem of restenosis.

The study, conducted by Jeffrey W. Moses, M.D. et al at the Lenox Hill Heart and Vascular Institute of New York City, seeks to verify preliminary reports of successful reduction in restenosis by sirolimus-eluting stents. There has been evidence since the early to mid-1900s of sirolimus as a potential inhibitor of the proliferation of vascular smooth-muscle cells and therefore, also an inhibitor of coronary-artery restenosis. (Marks) But there have been relatively few conclusive studies thus far. This trial was important procedurely because it was a randomized, doubleblind comparison of sirolimus-eluting stents(SES) and the standard bare metal stent (BMS) in patients newly diagnosed with lesions in the native coronary artery. In additional to its better design, it followed patients for a longer period of time and patients involved were afflicted with more complicated and challenging conditions such as higher frequency of cardiac risk factors (especially diabetes), more complex lesion morphology, and longer lesions. In short, it better imitated typical patients found in clinical practice.

Even with the increased complexity of the patients’ health conditions, the study found that sirolimus-eluting stents are indeed more effective and less harmful than the standard. The study demonstrated a suppression of in-stent neointimal hyperplasia, the abnormal growth of new tissue over a stent. There were no untoward angiographic complications such as late aneurysms. Finally, the rates of adverse clinical events such as thromboses were not significantly higher in the sirolimus-eluting stent group than in the standard stent-group.

These results indicate that sirolimus-eluting stents simultaneously preserve the safety of stenting procedures while improving the efficacy. This gives us hope that this success will lead to further innovations and technologies in the realm of coronary therapy in the future.

Blog #5

Morice, Marie-Claude at el. The New England Journal Of Medicine. “A Randomized Comparison of a Sirolimus-Eluting Stent with a Standard Stent for Coronary Revascularization” June 6^th 2002.

<http://nejm.highwire.org/cgi/content/full/346/23/1773>

This clinical study compared the effects of traditional bare metal stents to a sirolimus eluting stent. The previous post examines the effectiveness of a herapin coated stent, and this article examines a different drug to use in the drug-eluting stents. The sirolimus eluting stent was a relatively new design intended to slow cell growth within the stent that resulted in restenosis. The stent is designed with a polymer coating impregnated with the drug covered by another polymer layer. The stent was designed to release 80% of the drug within 30 days. The subjects were tested for percentage stenosis after 6 months. The drug eluting stents arteries had a greatly reduced amount of restenosis after 6 months. This article was a seminal study- one of the first to show a significant reduction in occurrence of restenosis, the “Achilles heal” of angioplasty and stenting, with the use of a this specific drug, sirolimus, embedded in a delivery polymer.

(http://nejm.highwire.org/content/vol346/issue23/images/medium/03f1.gif)

The experimentation with drug eluting stents represents an important development. It represents the process of finding problems with medical procedures and trying to improve those procedures. Balloon angioplasty helped solve the problem of obstructed arteries. When there were issues with vessel collapse and subsequent acute closure and, metal stents were introduced to solve that problem but were only slightly effection for cell buildup and restenosis. When cell growth and restenosis were still an issue, the drug eluting stent was developed to further address this problem. By the looks of this article, drug-eluting stents were an efficient solution to the issues associated with bare metal stents.

It appears from this article that drug-eluting stents are a more effective solution to the problem of restenosis, and a preferable treatment to the bare metal stents. There was a lower occurrence of adverse effects defined as “death, myocardial infarction, coronary-artery bypass grafting, and revascularization of the target lesion or vessel” in the drug eluting stents compared to the traditional stents. An issue with the report is that it only compares the two groups of patients over 6 months. These stents are designed to be a relatively permanent solution to the arterial obstruction. In order to truly justify the usage of drug-eluting stents over the traditional bare metal stents or even balloon angioplasty, studies must follow the patients for an extended amount of time, even years after the implementation of this biotechnology. This article fits into the current health care debate by examining one of the many drugs to be used in drug eluting stents. The specific benefits and issues with the different drugs will help establish when specific drugs are going to be used. Thus following article also examines sirolimus eluting stents, but over a slightly greater period of time.

Blog #4

Serruys, Patrick W. et al. "Randomized comparison of implantation of herapin-coated stents with balloon angioplasty in selected patients with coronary artery disease." Lancet. 352. August 29 (1998): 673-81. Print.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1B-3TW6XCJ-3&_user=489286&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1121249342&_rerunOrigin=scholar.google&_acct=C000022678&_version=1&_urlVersion=0&_userid=489286&md5=4dfecd94f54de1b53aad89806b064f43

This article, from the August 1998 volume of The Lancet, one of the world’s leading general medical journals, presents yet another study on the effectiveness of stents versus balloon angioplasties. As has been previously determined, stenting has a preventive effect on restenosis and acute closure and therefore is more desirable than balloon angioplasties. This study also confirms what was discussed in the previous post with regards to the combined use of two anitplatelet drugs, aspirin and ticlopidine. This combination is safe and effective in preventing stent thrombosis.

Also assessed in this study was the relative cost-efficacy of stent implantation and balloon angioplasty. Answers are not yet conclusive. Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is indeed more effective but also significantly more costly than balloon angioplasty. The assessment of cost-effectiveness is never without some debate. Typically, cost-effectiveness analysis concentrates on life-years gained and quality-adjusted life-years gained. Therefore, long-term follow-up over many years is necessary to fully assess the relative value of a particular intervention. At the time this article was published, there had not been enough time for long-term follow-up. Nevertheless, we have good reason to believe and other data to support the notion that stent-implantation is superior to balloon angioplasty in the long-term as well.

In addition, study authors found that the current price of the stent and delivery system has such a prominent role that stenting could be made significantly more cost-worthy simply by reducing the price of the device. As more studies are completed, we are finding more proof of the efficacy and safety of stent implantation. As the success of this strategy continues, the medical world’s trust as well as that of the public will grow. Hopefully this will lead to more widespread implementation and therefore more cost-effective practice. As the stent implantation becomes more prominent it should be available to every potential recipient without the worry of cost.

Blog #3

Leon MB, Baim DS, Popma JJ, et al. New England Journal of Medicine. “A Clinical Trial Comparing Three Antithrombotic-Drug Regimens after Coronary-Artery Stenting”. 1998;339:1665-71

http://content.nejm.org/cgi/content/abstract/339/23/1665,

By the publication of this article in 1998, coronary-stenting that we discussed in previous blogs had become commonplace. Frequent use of coronary stenting had been accompanied by intense anticoagulant drug regimens, such as “intravenous low-molecular-weight dextran, oral aspirin and dipyridamole, and intravenous heparin followed by oral warfarin” (Leon MB). These drugs were effective, but resulted in prolonged hospital stays and occasional vascular problems. This study suggests the utilization of less aggressive antithrombotic drugs regimens. This article compares the effectiveness and safety of three different antithrombotic drugs. This trial is an attempt to address the main complication of coronary stenting, stent thrombosis, with mildly gentler drugs. The three antithrombotic drug treatments, aspirin, aspirin and warfarin, and aspirin and ticlopidine, were administered directly after stenting and then compared by examining incidence of stent thrombosis. Results showed that treatment with the aspirin and ticlopidine more effectively reduced stent thrombosis than aspirin alone, or aspirin and warfarin. But, it was also found that administration of aspirin and ticlopine slightly elevated risk of excessive bleeding and vascular surgical problems as compared to aspirin alone. This article is in disagreement with other studies claiming that the combination of aspirin and ticlopine had a lower incidence of vascular surgical problems than therapy with aspirin and warfarin. This study shows that the two separate drug regimens had similar incidences of vascular surgical complication. While this article suggests aspirin and ticlopidine as a milder, but still effective, drug regimen for reducing stent thrombosis, the regimen is not without its health risks. Aspirin and ticlopine provide the medical community and its patients with a good, but not a perfect alternative to aggressive anticoagulant/antithrombotic drugs. They do not address the problem of neointima hyperplasia or restenosis, which is largely unaffected by the antithrombotic regimen. Following this study, researchers would continue to search for different treatments that both prevent stent thrombosis and other risk factors, including neointima hyperplasia.

Blog #2

Fischman DL, Leon MB, Baim DS, et al. New England Journal of Medine. “A Randomized Comparison of Coronary-Stent Placement and Balloon Angioplasty in the Treatment of Coronary Artery Disease”. 1994; 331:496-501

http://nejm.highwire.org/cgi/content/full/331/8/496

This 1994 clinical study compares the effectiveness of old, standard balloon angioplasty(BA) versus a new method of implanting metal, balloon-expandable stents. Most studies preceding this test focused on simple balloon angioplasty with the major limitations being acute collapse of the vessel (acute closure) or later scar formation or restenosis, as nnoted above. Attempting to deal with these critical issues, other techniques where developed including atherectomy, or removal of plaque from the arteries, as a method of preventing restenosis. However atherectomy proved ineffective, and this article explores stents as an alternate way to reduce restenosis. The results of this test showed that the new technique reduced not only the incidence of restenosis after the procedure, but also the need for patients to undergo addition revascularizations. The study informs its readers that while the stents are more effective at preserving the width of the artery, and preventing restenosis than standard balloon angioplasty, there are certainly some limitations associated with this new therapy. These metal stents are not all-powerful, they do not reduce the rate of future coronary events any more than a normal balloon angioplasty. On a similar note, implanted stents can induce thrombosis. For this reason, it becomes necessary for the patient to go on antiplatelet agents. Potent anticoagulants can result in further peripheral vascular problems and critical issues with bleeding. Although this new therapy unquestionably reduces the need for the patient to receive multiple balloon angioplasties, it could increase mortality due to stent thrombosis. This article was probably read mostly by physicians, given that it appeared in the New England Journal of Medicine, and it was reported in the lay press as it was interest to the general public as well. The medical world, including health organizations and sectors of the government, most likely had mixed views about this test. It presented the biomedical community with a new, effective alternative, but not without health risks which would need to be addressed as separate problems. Similarly, the public probably anticipated the new coronary-stent technique with both hope and anxiety. The federal government and insurers were certainly torn between the desire for a treatment that reduced the need for follow-up angioplasties, but resulted in large increase in cost related to the new stents. Stents are still widely used, but people with the stents have to take drugs to prevent thrombosis, or blood clots. The following post addresses the efficiency of several antithrombotic drugs to help improve the lives of patients with stents.

Blog #1

Serruys W Patrick at el. The New England Journal Of Medicine. “A Comparison of Balloon-Expandable-Stent Implantation with Balloon Angioplasty in Patients with Coronary Artery Disease” August 25^th, 1994

<http://nejm.highwire.org/cgi/content/full/331/8/489>

This study came at a crucial time during the development of stents. This article examines the trade offs between fear of thrombosis and side effects of the stents compared to the need for multiple surgeries after a normal balloon angioplasty. It focuses on the comparison between those treated with the traditional balloon angioplasty to those treated with the relatively new biotechnology, metal stents. More specifically, it expands on the previous post by examining when members of each group reached an “endpoint” defined in the article as “death, … a cerebrovascular accident, myocardial infarction, …coronary-artery bypass surgery, or a second percutaneous intervention” within seven months. The results show that there was a slightly lower occurrence of an endpoint (20% vs. 30%) and a lower incidence of tissue growth, or restenosis within the group that received the stents.

This article traces important events in the history of cardiovascular surgery. Balloon angioplasties were developed to open blocked arteries. The balloon angioplasties were highly effective, but there were several common side effects. Restenosis (blockage by cell regrowth), plaque buildup and stiffening of the arteries are all issues related to a PCI. In order to solve the problem of restenosis, metal stents were developed. This study compares the efficacy of the two procedures that try to deal with arterial blockage. The comparison is controversial because even though metal stents prevent most restenosis, the patient must take blood thinners to prevent thrombosis. The blood thinners can lead to additional vascular problems. Implementation of a metal stent also results in a longer hospital stay. This study describes the pros and cons of metal stents and represents the ubiquitous medical issue of weighing benefits against side effects.

It is interesting to see how a medical procedures gain support in the medical world. Metal stents are widely used today, but at one point they were (and still are to a degree) controversial. Studies such as this one helped establish the wide spread usage of metal stents by demonstrating their efficiency over previous procedures. This article fits into the current health care issues by examining the issues that patients with stents deal with every day.

Overview

Our blog will be examining the development 2^nd and 3^rd generation drug eluting stents and the history leading up to it. The articles from our first six blogs were discovered from one main source, “Coronary Interventional Equipment and Techniques”, UptoDate. We then used the bibliography from two overview chapters to discover the articles we considered relevant for the history progression of coronary artery stents. We hope that these blogs will give an effective progression of how to solve the different coronary artery risk factors using angioplasty and percutaneous coronary intervention (PCI)