Friday, May 15, 2009


When I was training in UK in 1977 ( guess my age then ) one of my consultant hematologist in Glasgow Royal Infirmary, UK,one day informed us that he was travelling to USA, to present a paper at the American cardiology meeting. Being a bit blur then ( those were my younger days ), I never asked which society or which meeting. Also an Asian with a UK consultant at that time, you listen and don't ask too many questions. Anyway, that was also when I learned that cardiology is closely related to hematology, through a process called " atherothrombosis " , basically the cause of all our acute coronary events. From henceford, cardiologist must also understand a fair bit of hematology, especially those parts that has to do with coagulation and blood clotting. In fact, I often joke with our hematologist that cardiologist know more about anti-platelets then the hematologist. When the early aspirin studies first came out, to show that aspirin prevents heart attacks, it was also in many ways a proof of concept. Those early, very elegant work done by Dr M Davis, really make the point very clearly that rupture plagues are obviously a danger to all of us and the cause of many cardiac deaths, and aspirin can prevent that.
We then went thru a phase of developing alternatives as aspirin has this nasty side effects of gastrotoxicity. Ticlopidine, working as a ADP receptor blocker was good. Better than aspirin in terms of efficacy but had the bad side effects of leucopenia, which could kill. I had two female patients ( both post coronary stenting ) who died of leucopenia following the use of ticlid.
Clopidogrel is obviously a very potent anti-platelet agent, also working via the ADP pathway. It is effective and we still use alot of it, especially post DES implantation. We now also realise that Clopidogrel, good as it is does suffer from a few drawbacks, like platelet resistance ( which may have a genetic basis ) and also the fact that its effects are non-reversible. Once clopidogrel goes in, it stays for the whole life of the platelet of about 7-10 days. There is of course also the issue of cost, as clopidogrel is RM8 per tablet ( estimate ).
I think the last drawback, cannot be avoided ( we call it progress ).
Last year saw the launch of prasugrel, following the TIMI 38-Triton study. However, prasugrel, powerful as it is comes with the downside of extra bleeding and its action is also non-reversible
There are however, new anti-platelet agents being developed that will be as powerful as prasugrel, with less platelet resistance and also whose effects on the platelet may be reversible. This week saw the preliminary results of two trials, the CHAMPION-PLATFORM and the PLATO trial, featuring the anti-platelet agent IV Cangrelor and the the oral agent Ticagrelor respectively. It would appear that these two agents, work by a different pathway, blocking the P2Y12 pathway, and is reversible. Looks like IV Cangrelor does not work well but the Phase 3 results of Plato ( Oral Ticagrelor ) may be favourable and will be announced at ESC in September.
Looks like all many pharmas are racing to find a replacement for clopidogrel, as cardiologists are very concern about this issue of clopidogrel resistance. It also means that the days of clopidogrel are numbered, even more so with generics now well on our shores.

No comments: