Friday, March 04, 2011


One of the phenomena that we interventionist have yet to understand well is the issue of late stent thrombosis, especially with drug eluting stents. Why do stents, implanted 3-4 years ago, suddenly thrombose and cause an AMI? This is seen in bare metal stents as well, but much less. You see, we have always thought that after you implant a stent, there will be healing, fibrosis or in our language, neo-intimal hyperplasia, which gave us the problem of restenosis, which we did not want. So, the workers in Brazil and Netherlands, worked on drug coated stents to stop neo-intimal hyperplasia, and stop stent re-stenosis. They were successful and so we see the advent of drug coated stents. In Barcelona 2006, we learned to our horror, that with DES ( Drug Eluting Stents ), we no longer have the problem of restenosis, but we exchanged that for a problem of stent thrombosis, especially late stent thrombosis, and we were trying to answer why? We thought that it was the polymer, and so many second and third generation DES are now polymerless. We thought that it was the premature discontinuation of Clopidogrel. This is certainly true. But how long do we need to keep the clopidogrel? Now we may have another part of the answer to this puzzle.
While doing my reading this week, I came across this interesting paper by Dr Renu Vermani's group at CV Path, Maryland. The paper is entitled "The pathology of neoatherosclerosis in human coronary implants". In the J Am Coll Cardiol March 2 online edition. The lead author here is Dr G Nakazawa, who works with Dr Vermani. We all recognise Dr Vermani for her seminal work on stent thrombosis, way back in the mid 2000, acting as our conscience to see what we are doing wrong, in our endeavor to improve patient care. All that we see clinically, is not what they see, post mortem, and you cannot argue against post-mortem findings. When properly done, they are final.
Anyway, Dr Nakazawa and colleagues, studied 299 consecutive autopsies, of patients who have died post stenting, DES and bare metal. They went through 400 lesions. These were all patients who had their stents implanted, months or years earlier. They found that in those who had DES implanted, with the stent healing comes re-atherosclerosis or the authors call it neo-atherosclerosis. This is twice more likely with DES than with bare metal stents. I like re-atherosclerosis because, we thought that with stenting, we have exchanged atherosclerotic lesion with scar tissue formation and re-endothelisation ( the atherosclerotic plaque was digested away by the macrophages following stenting. With DES, plenty of re-endothelialisation and with bare metal stent, plenty of neo-intimal hypertplasia. Now we know that that is not true. Following stenting, after scar tissue, we again get re-atherosclerosis. With DES, this re-atherosclerosis seem to come earlier ( almost by a factor of 3 ), and it appears to be more aggressive, with thinner fibro-atheroma caps, and more prone to plaque rupture. With bare metal stents, there is thicker fibro-atheroma caps and less prone to rupture. They also noted that with bare metal stents, the re-atherosclerosis takes longer to form ( delayed by almost 3 years ) and with DES, it takes faster to form. Basically, the old disease comes back, and with DES, it comes back with a vengeance. The bad news is, that DES is good, and also is a temporary solution. Bare metal stents, may need a re-do, but is a longer ( at least from the re-atherosclerosis point ) temporary solution, but shorter from the re-stenosis point.
However, the good news is ( as I see it ), there is another chance for us, besides intensive anti-platelet therapy, to also institute, intensive statins, and other plaque cooling agents to lessen inflammation. Of course all these go along with intensive life style modifications, etc., etc., etc..
I also wonder what impact this new findings will have on the new ABSORB stent, or the bio-absorbable stents that are now in development. Will bio-absorbable stents also run the risk of re-atherosclerosis after the stent have melted away? Then we are back to square one again.
How amazing, PCI, like CABG is only a temporalising solution. It is not a cure, just a temporary relief, for us to get our lives back on track again. To give us a second chance, so to speak. Intensive medical therapy is still the main stay of treatment for coronary artery disease.

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