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).