Friday, October 01, 2010


Last weekend saw the conclusion of TCT 2010 at Washington. TCT stands for Transcatheter Therapeutics a meeting organised ( very successfully ) by the Cardiovascular Research Foundation of USA. It showpieces all the latest advances in the field of interventional cardiology, and now even beyond that into the field of percutaneous valve replacement ( TAVI ), percutaneous peripheral vascular angioplasty, and also cerebral artery and carotid artery interventions. This TCT 2010 meeting saw many papers and presentations on the latest in Drug Eluting Stents ( DES ) clinical data. So I thought that I should do an update on this, having seen the scene evolved so rapidly over 33 years from a simple balloon angioplasty done using a balloon made in a kitchen, to bioabsorbable stents ( 2 year followup data ).
It may be good ( especially for those not initiated, or not in this line ), for me to step back and recall the events from September 1977 till now.

September 1977 saw the first attempt by Dr A. Greuntzig of Zurich, Switzerland, to successfully treat a proximal LAD stenosis in a middle age dentist. That procedure lasted him 20years, till the dentist developed re-stenosis and required a second procedure when a bare metal stent was implanted, which lasted 6 months ( to the embarassment of the interventional cardiologist, who was also the assistant to Dr Greutzig at the first balloon angioplasty ). Anyway, from the 1977 experience, we saw the birth of a new branch of cardiology called interventional cardiology and we all became "bal-lunatics" ( balloon lunatics). It also saw the establishment of " live demo" courses to quickly teach this new branch of medicine so that it can benefit cardiac patients ( or did it benefit cardiac doctors ). The whole discipline mushroomed and the procedure became immensely popular ( not to forget that the alternative was either medical therapy or the traumatic by-pass surgery ). Then we learned that however good or careful you are, there is a 40-50% chance of the dilated lesion re-narrowing again, and a 4% chance that during the procedure, you may dissect the artery and result in an acute heart attack and the need for emergency bypass surgery. We use to have to keep an open heart theater waiting, a cardio-surgical team on standby, while we work in the angio suite. This went on until we developed the stents. These were basically surgical grade stainless steel, bare-metal scaffoldings that could prop up artery walls and prevent them from collapsing ( in the event of a major dissection ) and because of them we dare to open the artery bigger and more aggressively, thereby reducing the chance for re-narrowing ( from 40-50% to 15-20%, on an average ). Re-narrowing following stenting with bare-metal stents was a result of tissue overgrowth ( scar tissue ), in those patients who were proned ( not everyone, only 20-30% of patients treated ). Also with the advent of the stents, acute closure ( acute heart attacks ) was a thing of the past and we could work without having an open heart theater on the ready ( although it would be nice if there is an open heart theater in the same facility ).
We then realise that a 20% re-narrowing rate was still not good enough and innovators worked feverishly to try and lessen this problem of re-narrowing following ballooning and stenting ( bare-metal ). Taking a page out of cancer chemotherapy, the innovators discovered that coating the bare metal stent, with a layer of chemotherapy ( cytotoxic paclitaxel or cytostatic sirolimus ) was practical, safe and effective, to limit tissue over-growth, and so limit or prevent re-narrowing. To allow the drug coated on to be released in a controlled predictable manner ( just like with oral tablets ingested ), the drug has to be coated with a polymer ( to control its release ). So now, with drug eluting stents ( DES ), you have the drug, coated on the stent ( bare metal ), and covered by a thin polymer coating. This was the first generation DES, as exemplified by the CYPHER stent and the TAXUS stent. Because the chemotherapy drug was delaying the tissue healing ( which is a protective mechanism by the body, to protect the integrity of the artery wall ), patients after DES had to take dual blood-thinning, anti-platelet agents. Initially, we were recommending dual anti-platelet medications for 3-6months. In September 2006, at the European Society of Cardiology Congress, it was reported that some patients were getting heart attacks following implantation of DES, months or even years after the procedure. Further research found that this was because, the artery wall healing was incomplete and the patients had stopped their blood thinning to early. Researchers also discovered that this delayed tissue healing was partly due to the drug effect ( the purpose of the drug ) and partly due to artery wall allergic reaction to the polymer coating. The search then began, to try and develop a technology of having a drug coated on the stent, either without the polymer, or with a polymer that can be absorbed back into the body ( and disposed by the body's scavenging system ). Some companies are so smart that they can coat the drug on the stent, with an absorbable polymer only on the vessel wall side of the stent ( where the action for the drug is ). These formed the second generation DES, as exemplified by Endeavour, Endeavour Resolute, Xience V. Xience Prime, Biomatrix Flex, Taxus Promus, Taxus Element. One company actually tried to harness the body's own healing cells and tried to encourage a natural ( or artificially natural ) healing of the vessel wall after the injury with the stent implantation. The evidence released in TCT 2010 on this Genous stent, showed that this did not work well. The clinical trial data ( TRIAS HR ) comparing the Genous stent with the Taxus stent showed that the Genous stent was inferior to the Taxus stent. Obviously much more work needed to be done with the Genous stent. It is not so easy to imitate God's healing process.
So TCT 2010 revealed many comparative clinical trial data, comparing many of the DES. I sat down and looked through the numbers and came out with the " DES-O-Meter " which I believe is a simple way to illustrate where each of the well studied DES stand. Obviously there are many other DES that are not in the chart. It also means that the good reliable data on them is sparse, or very sparse and so using them is at one's own risk. This big 5, are well studied, proven safe and good. Maybe cost a bit more. If your doctor has used a stent for you that is not on the list, you know what it means. The stent with many arrows pointing towards it, is obviously very popular and many like to compare against them ( bench-marking ). The words in the arrow refer to the clinical trials which arrived at the conclusion, and the positive sign at the end of the arrow shows that that stent is proven superior by those trials. Stents with few arrows involving it shows that there is a lack of good evidence. We all hope that it is not a one off?

Nonetheless, this is not the end of the story. TCT 2010 also saw the presentation ( on Friday ) of the early pilot trial data on the ABSORB. This is a biodegradable DES, owned by Abbott Vascular. The early data seem promising, but still not quite good enough. Suffice to say that this 3rd generation DES is under serious study and I am sure that we will soon ( next 5 years ) see the use of a DES that is biodegradable and totally absorbed back in to the body's scavenging system, after 6 months, so that there is no stent left. The stent and drug just do their work in 6 months and disappear. How nice? The 2 years data on the first cohort, is so so. The 6 months data on the 2nd cohort is so, so, so we have to wait for more corrections and more work.

Interventional cardiology marches on, to give better treatment options to our patients. They are all good, when properly applied, but are they all good? In away, only time will tell. Needless to say, there is a cost to pay.

We live longer and better, at a cost. Is it worth it? Each of us must answer for yourself.

No comments: