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)