ANTI-PLATELET AGENTS, UPDATES

As I was looking over the medical literature and also after the weekend with Astra-Zeneca, I realised that the push in anti-platelet therapy is towards better monitoring, of anti-platelet activity and also the coming of new agents. The issue of bed-side identification of who is a responder and who is a hypo-responder, by genetic testing, seemed to have waned. Maybe it is not practical.
To begin with, lets establish that anti-platelet agents are basically blood thinners for the arterial system, where blood clots form primarily from rupture or tear ( loss of the integrity of the endothelium ). This is not the same as blood clots in the venous system or cardiac chambers, where blood clots form from blood clooting factors or stasis. This latter require warfarin or warfarin like drugs.
Since 2006, interventionist in particular have been struggling with this issue of stent thrombosis., be it subacute or late. It would appear that the acute stent thrombosis that we see, so occasionally now, is invariably due to technical factors at implantation. And the very late stent thrombosis and maybe also some of the reasons for late stent thrombosis, could be due to the polymers and reactions to the polymers of the DES ( drug-eluting stents ).
So far, it appears that the issues of subacute and late stent thrombosis maybe related to the lack of anti-platelet activity of the anti-platelet agents used. That gave rise to the efforts to find out which patient do not respond well to anti-platelet agents, primarily clopidogrel. We rely so heavily on clopidogrel. This search resulted in the findings that some of us carry a gene which make us hyporesponders to clopidogrel, the CYP 2C19 gene. There were attempts to produce some rapid kit to identify these people. Looks like that effort did not quite catch on, at the moment. Some of us just take the easy way out. If we should suspect clopidogrel hyporesponders, we just double the dose of clopidogrel. That is not my purpose on this blog.
I wanted to highlight that looks like much effort is being undertaken to produce a bedside kit to assess the efficacy of clopidogrel by the bedside. Back in 2006, when I enquired about this bedside kits, they were cumbersome to use, and not so easy to standardise, resulting in many inaccuracies. However, many recent publications seem to suggest that there are simpler and better kits out nowadays, to see the degree of platelet aggregation follwoing a dose of clopidogrel. A recent paper by Dr Dirk sibbing of Munich Germany, in the Journal of the American College of Cardiology, July 20th suggest that this is feasible and gave an accurate assessment of anti-platelet activity, allowing us to identify the hyporesponders ( platelet aggregate count of 468 or more, just before PCI ) or the hyper-responders ( aggregate count of <188 ). Of course, should the count be too high, it means more clots and thrombosis, and if the counts are too low, it means a higher risk of bleeding. I also heard this point being made over the weekend by Dr Gilles Montalescot.
Of course, so as to give our patients a choice, new drugs are also being developed where hopefully, we do not have this problem of non-responders to a drug. I think this is a wishy dream. The new drug being talked about more and more is ticagrelor, a new fast acting, non-prodrug, with good anti-platelet activity which is reversible to stopping of the drug. How ideal? But always remember, that fast on, fast off also has its problems, principal of which is loss of drug activity should you forget one or two doses.
Of course, the bottomline is that with medical progress and better therapy, the cost goes up. So what is new?