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.