The state of DES at end 2007

We started to use the first DES, the Cypher stent (JnJ cordis) on 28th May 2002. The Cypher was FDA approved in 2003, and the Taxus (Boston Scientific) was approved in 2004. These two must form the 1st generation DES. From these two, we have learned much, including an excellent short term (1 year) result. The SAST (subacute stent thrombosis) rate of 1-4% and a restenosis rate of <5%. This was very good compared to the bare metal stent which had figures of 1-4% and 15-20% respectively. ( * Thrombosis is blood clotting, and stent thrombosis is blood clots forming in stents ).

There was a time from 2003 to 2006 when we felt that we could DES everything. DES was then proclaimed as a revolution in CAD treatment. The cliche then was that everyone (meaning everyone who could afford) should get a DES. DES usage then climbed to almost 95% in some institution, both at home and abroad. Then came the fall of 2005, and the summer of 2006, when we began to hear murmurings of problems with DES. The Europeans began to produce reports of late and very late stent thrombosis with DES. The shares of JnJ and Boston duly fell. DES usage declined, both at home and abroad. DES usage in some centers fall to almost 50-60%.
Now, the summer and fall of 2007 brought some silver-lining. Many reports began to appear, which showed that DES stent thrombosis was not unique to DES but was also seen, in similar proportions, with bare-metal stents. In fact, the FDA had at a December meeting, come to the same conclusion. They identified that when DES was used as labelled by FDA, there are no problems. It is the off-label use that is of some concern. Looks like the clouds are lifting on the DES-stent thrombosis issue. In short, there are no problems with DES use if it is used as labelled. When the cardiologist wishes to use it off label, they must be more circumspect and think twice. The use of plavix had gain prominence, as many of the DES-thrombosis problem maybe due to premature discontinuation of plavix.

The other good news in Novenber, December 2007, is the FDA advisory panel approval of two new DES, namely the Endeavor stent (Metronic International), and the XienceV stent (Abbott Vascular). These two stents can be called a second generation DES. Their stent platform is cobalt chromium base (as opposed to stainless steel base for the cypher and taxus). The advantage of cobalt chromium is that is a very strong alloy, allowing the company to make the stent struts very thin and low-profile, while retaining it's radial strength. This translated clinically into a stent with low stent restenosis rate (even on bare-metal), a more deliverable stent and probably a stent with lower stent thrombosis. The plain (non-drug coated) bare-metal cobalt chromium stents had half the restenosis rate of the old stainless steel bare-metal stents. In fact the plain (non-drug coated) cobalt chromium stents had a restenosis rate of only twice that of DES. The results so far of the cobalt chromium DES shows that there seemed to be less stent thrombosis and a lower restenosis rate. Looks like the second generation DES is definitely better than the first generation. What more, there is no increase in price. In fact, the first generation, were a bit more expensive. This is thus good news for the patients.

I am sure that with more innovations, the third generation DES will even be better. But first, I think that we will be seeing more second generation DES coming to our shores soon. So much better for our patients. I hope that the price will come down further.

DES; More Lessons Learnt

In 2001, DES was hailed as the revolution in Interventional Cardiology. Now 6 years later, it is viewed with suspicion by the lay public and caution by the interventional fraternity, ever since the infamous presentations by the Berne-Rotterdam axis at the September 2006 meeting of the European Society of Cardiology. Many in Interventional Cardiology, bombarded by skeptics (no shortage of them) who prophesied the last days of DES, feel that perhaps the using bare-metal stents (BMS) is not such a bad idea after all. They have very quickly forgotten the days when every 3rd to 4th patients after BMS, will return for re-vascularisation. Perhaps the blessing in disguise for us, balloonatics, is that we have become more circumspect about using DES. We exercise greater caution is choosing the right patients for the DES (not just affordability alone).

The JAMA vol 297, year 2007, carried two DES registry reports which to me merit watching. I suppose the authors of the paper were trying to answer the question, does "off-label use " of DES contribute to the greater MACE events. Most of us will reflexly say yes. Using the DES in situations where they were not proven to be effective and safe, must run the risk of more failures and adverse events. The message for us "balloonatics " is that when you use a DES "off-label" be prepared to accept more late stent thrombosis, uncertainty in the duration of Plavix, and possible more re-stenosis and other adverse events. Put another way, use DES "on-label " to avoid undue problems. Maybe many are doing that, for the market news is that the usage of DES has dropped and the usage of BMS has increase. I do hope that all this will translate to better patient care.

Hmatter FAQ on DES

Note: This FAQ is the Hmatter opinion on DES. If you'd like to use it somewhere else then let us know by telling us in comments where you'd like to post this.



FAQ ON DES (Drug Eluting Stents)



Having been implanting DES since the year 2002, the initial euphoria is slowly dying down. More people, including those not on already DES are asking questions about DES. When we first started, there was only the Cypher (JnJ) stent. After that, came the Taxus (Boston Scientific) Stent.



Now we have the Endeavor (AVE metronic), The Coroflex Please (B Braun), and more recently the XienceV (Abbott) stent. The first two are FDA and CE mark approved, while the latter three are only CE mark approved. There are a few more DES that are CE mark approved only like the Genous (Orbus Niche), the Costar (Conors), and many others (some I don't even know). The marketplace here is getting very crowded.



Patients and potential patients are asking more questions about these DES. This curiosity is in no small way driven by the heavy press coverage in the media. Since bad news sells it follows that most of this is misinformation. After Barcelona 2006 one media outlet trumpetted "Timebomb in your heart". How sensational, how eyecatching, how misleading. They have their job to do and in order to do their job the maxim "if it bleeds then it leads" obviously sells more papers or catches more eyeballs.



I certainly feel that these kind of sensational headlines are plain unfair and irresponsible. These are the top 3 questions are most often asked.



Q. Doc, I hear that these new medicated stents are killing patients?

A. There is no evidence to say that DES have a higher mortality when compared to the use of bare metal stent ( BMS ). This conclusion was arrived at by the expert panel, chaired by the circulatory device committee of the FDA. After looking into all the data, the expert panel concluded that although late stent thrombosis was more frequent with DES, there were no increase mortality.



Q. Will the stent move after implantation, and can it be removed and changed, if they block off?

A. No, once properly implanted, the present type of DES will neither move, nor can they be removed and replaced. There is ongoing research to invent a DES that is absorbable like the sutures that surgeon presently use in surgeries, eg in gallbladder removal, or worm removal. However, the present absorbable DES being tried, have not yielded good enough results, although they seemed safe to use.



Q. Must I take medicine after DES, if so, what kind?

A. After DES implantation, the patient will need to take, heart artery relaxing pills like calcium channel blockers (e.g. diltiazem). They will also need blood thinning pills, including aspirin and Plavix. Dual anti-platelet therapy (aspirin and plavix) is absolutely vital. Both for 6 months at least, and thereafter, plavix for the next 6 months. So the total length of plavix should be 1 year at least. Some patients may need to have plavix even for longer. Patients who are know to be allergic to plavix, should not get DES.



Then there are the other medications for preventing heart artery disease like cholesterol lowering medications, and where necessary, blood pressure and diabetic pills. Let us emphasize that plavix for 1 year is absolutely vital, as the majority of patients who suffer late stent thrombosis after DES, are those who had prematurely stopped their plavix.



I hope that this will help. If there are other questions that need answers, please feel free to ask. Do not let unfounded fears keep you from benefiting from DES.

Euphoria to Panic, the story of DES

I implanted my first DES, a Cypher, on May 28th 2002. Since that period of euphoria, we have seen a descent in the fortunes of DES to considerable trials and tribulations.

Initially there was a period of euphoria spanning 2002. After that, we started to see problems with the Cypher stent in the form of thrombosis. Bad news sells, predictably, the mass media picked it up. JnJ Cordis called upon their expert panels who came out to make the right reassuring noises and all was calm for a while.

Like a bad movie, a calm can only mean one thing, an impending storm. Storm it did when the Cypher stent picked up in popularity. Suddenly JnJ Cordis went from defending the Cypher to trying to figure out how to churn out more of the things because they just couldn't keep up with demand. Centers started to ration the usage of Cypher. In hindsight this was probably a good thing, usage of Cypher was rationed and bare metal stents picked up the rest of the slack resulting in more usage.

Next the FDA approved the use of Taxus. After about a year or so reports started coming out that Taxus stent balloons were not deflating. Unfortunately, some patients suffered heart attacks and a few did not make it. Boston Scientific pro-actively withdrew the affected batches and issued statements of reassurance. The stents seemed to work well after this (around 2004).

In 2005 Dr Virmani sounded off about potential dangers of DES. She had become an expert in studying necropsy specimens of DES failures. She began to warn us that DES caused terrible reactions in the coronary arterial wall, including inflammatory responses which looked like allergy, inadequate expansion of DES with arterial wall malapposition, and of course the all important stent thrombosis. We all thought that of the millions of DES placed, these reports were the results of 40 necropsy specimens. We heard but paid only cursory attention to the information.

However, at meetings we began to hear of reports of stent thrombosing after 1 year of implantation. Until then, we thought that stent thrombosis was a problem of the first six months or 1 year of implantation.

In Yr 2005, we heard the presentation of the "Late Basket Trial " by the Swiss workers who warn that there seemed to be more late stent thrombosis (stent thrombosing after 1-2 years of implantation) in DES. Then came Barcelona in September 2006, with the reports of Dr Camezind and Normad, who did the meta-analysis that warned use of the dangers of late stent thrombosis.

Bad news continued to sell and the mass media was there to document every horrid detail. This is a natural result of a smaller, flatter world where the inevitable flow of information leads to greater transparency. Post Vioxx, we learnt an important lesson - come clean early, coming clean late could result in very expensive lawsuits.

This brings us to the present. I spoke in Langkawi last year at the ICF 2006 to local interventional cardiologist on this subject. I concluded by saying that through all the trials and tribulations, we learned the following :-

1. Use DES only when it is indicated, and not simply for convenience of style and that the patient can afford it

2. There is still a place for bare metal stents (BMS), especially in patients who may be allergic to plavix, patients who may be scheduled for non-cardiac surgery (plavix may have to be discontinued), in large coronary vessels where DES or BMS made no medical difference

3. That Plavix (or ADP receptor blockers, including ticlopidine) is absolutely important, and should not be discontinued for 1 year at least after implantation, if not 2 years (as in Harvard's Peter Bringham).

In my practice, patients are advised not to stop their plavix without telling me. This then is the situation till December 2006. Who knows what Yr 2007 will bring.

The real dangers of DES

These are some of my notes for a talk done at Andaman Datai. The setting was lovely and the service was very good.

I had posted earlier on the PCI Tsunami-equivalent that came from Barcelona in September 2006. We were all stunned by the Europeans (Dr Camezind and Dr Normand) who presented two meta-analysis of data from randomised trials of two FDA approved stents, viz Cypher and Taxus, coming to the conclusion that they were dangerous due to association with increased rate of late stent thrombosis (especially in patients who discontinued their clopidogrel). This translated to more heart attacks and death. Of course that was all on European soil at the World Congress of Cardiology Annual Scientific Session/European Congress of Cardiology Annual Scientific Session, meeting in Spain.

In October, across the Atlantic, at the TCT meeting in Washington, the Americans struck back, claiming poor data analysis and causing undue stress for patients. They stopped just short of calling the Europeans incompetent.

From my understanding, they both have a point. There seem to be a risk of late stent thrombosis with DES, but the risk of heart attacks and death is not any higher then in patients who received the bare metal stents. The European data analysis was difficult as they claimed that they were not given all the raw data that they needed. There is obviously an issue with the discontinuation of clopidogrel. Many of the late stent thrombosis occurred in patients who had stopped taking clopidogrel, for very many reasons. Then it became apparent that the use of clopidogrel (which is absolutely vital) following DES implantation, is not approved by FDA. It is an off-label use.

Of course, almost like in the movies, in comes the high priest (read FDA Advisory panel on Circulatory System Devices) to decide to see if there should be any change in the labelling and use of DES following all this hooha. This Panel (which has been criticised by some as a rather bias panel) met on 8th-9th Dec. Guess what, they decided that all is well and business as usual. Their findings have just been revealed on the internet.

The specifics. They deliberated at great length, heard about 25 presentations from all over the first world, and concluded, that DES use is associated with an increase incidence of late stent thrombosis, but not any increase in death or heart attacks, when compared to bare metal stents. It is important to note that all the randomised controlled trial were done 4-5 years ago, but the consensus definition for late stent thrombosis (LST) were just agreed to after the September Barcelona meeting.

This new consensus definition for LST, was formulated by an Academic Reserch Consortium (ARC), headed by academics from Harvard and including many world famous cardiac interventionist, who have substantial business in the companies which produce DES. HaHaHa. How great is the system? Of course, the ARC definition for LST is very tight requiring angiographic or necropsy confirmation for a diagnosis of LST. So the Circulatory System Devices Advisory Panel of FDA concluded that DES use is safe enough and nothing important needs be change in the labelling.

The companies (JnJ Cordis and Boston Scientific) breathed a heavy sigh of relief and the NYSE remain quiet on these shares. Life goes on. We have all learn our lessons. We have to be more vigilant and circimspect in our DES use. We must be very particular with the use of clopidogrel and patients must be adviced precisely about the use of clopidogrel. When bare metal stents can do the job with almost similar risk of restenosis, they should be prefered. Companies producing DES must be committed to more longer term post-market survillence, and monitoring and world patient registries must be kept.

The doctors who use "generic" DES, whose companies cannot do post market survillence must know that DES are not without their problems even in good quality controlled manufacturing plants with vigorous American quality control.

The cross Atlantic DES stent war, I am sure will continue. I don't think that we have heard the last word yet, although the great American "high priest" have spoken.

Drug coated balloons

When DES (Drug eluting stent) was first announced to the world in 2001, it was touted as a revolutionary advancement in PCI. This advancement would solve all problems of percutaneous coronary intervention for CAD. At that time, little did we all realise that altthough DES did solve the problem of re-stenosis, it created a new problem of late stent thrombosis, first highlighted to us by the Swiss in the Late Basket Trial, and now openly announced and debated in ESC/WCC in September in Barcelona and later again debated in TCT/Washington in October. This is now widely seen as the inter-Atlantic Stent-war.

It looks like there is an issue, a problem of late stent thrombosis with DES (much as the Washington Americans would not agree). It does look like the fact the DES lessens and delays re-endothelialisation, this fact actually promotes stent thrombosis, making deployment technique and the role of plavix, absolutely vital. Of course the patient mix is also important.

With that long intro, the latest issue of the New England Journal of Medicine, had an article by a group of Germans interventionist (I must say that this are the lesser known Germans in our circle), who studied 52 patients with in-stent restenosis following bare metal stents, who received treatment witha paclitexal coated balloon. They compared their results with the control group who were tretaed with plain old balloon angioplasty (POBA). Lo and behold, the paclitaxel coated balloon group had restenosis of about 5% as compared with the POBA-treated group who had a restenosis rate of 43%. POBA is one of the ways of treating restenosis of bare metal stents in the days before DES.

What is amazing is that a drug coated balloon, inflated over a lesion for about 1 min, can affect tissue reaponse in such a significant manner. Of course, we are all holding our breathes to see if we can achieve this good result in native, virgin lesions. We must note that an in-stent restenosis lesion is not like a native, virgin atherosclerosis lesion.

This paper is very interesting and I am sure that other groups will begin to do the same and perhaps a large scale clinical trial will result, either confirming or disputing this findings. What was also intriging for me was that this work was not broadcast on the world stage of TCT Washington.

We should probably also take some time on this blog to comment on the industry news that JnJ Cordis has acquired Conors (the owners of the Costar technology).