Thursday, July 29, 2010


Yesterday, the FDA approved the use of ticagrelor, in the management of STEMI and also unstable angina and NSTEMI. I suspect that the decision was made because of the obvious benefit sen with the use of ticagrelor, in the PLATO trial, that was announced in ESC 2009 in Barcelona, and also simultanoeusly published in New England Journal of Medicine then.
That means that there are now 3 ADP receptor blocking agents for us to use in the management of STEMI and NSTEMI. More competition and also allowing us to individualise therapy, should the need arises. Also, hopefully, competition will bring down price, as it should in a free market economy.
Ticagrelor is another platelet ADP receptor blocker, like clopidogrel and prasugrel. But thats where the similarity ends. Firstly, it is not a pro-drug, thereby avoiding the problem that we now see with clopidogrel ( the problem of hypo-responsiveness because of the 2C19 allelee ) and other potential d-drug interaction. Secondly, it does not stick so strongly in the ADP receptor, allowing a more rapid onset of action and also some reversibility in its action. That has obvious advantage in that patients with unstable angina with undetermined anatomy, can undergo PCI loaded with ticagrelor. In the event that the anatomy is unsuitable for PCI, the patient can savely undergo CABG without too much worry of excessive bleeding or excessive blood transfusion. At least that's the theory. I say "that is the theory" because in PLATO, there was an excessive amount of bleeding ( when compared to clopidogrel ), especially hemorrahgic strokes ( and that is worrying ), that has yet to find a suitable explanation. I think we saw a bit of that with prasugrel against clopidogrel too. Looks like clopidogrel causes bleeding but much less then the other two. Rapidly reversible effect of of ticagrelor also has a downside. Should unstable patients on patients on ticagrelor following DES inplantation forget 1 or 2 doses of ticagrelor, the stent could thrombose or the lesion could become unstable again.
Yes, there are also side effects that were noted, including dyspnea. The dyspnea is difficult to explain, but AstraZeneca ( the manufacturers ) say that the dyspnea is usually mild and also reversible on stopping the drug.
Of course, the other issue is cost. I do not thing that new medical advances come cheaply. I am sure that Astra Zeneca knows that too and will plan their marketing strategy accordingly.
All in all, there is now a third ( I expect it to come to Malaysia soon ), ADP receptor blocker, anti-platelet agent. There are now 5 anti-platelet agents.
Not surprisingly since, CAD is so common and deadly, and anti-platelet therapy is so essential in the management.
Welcome aboard Ticagrelor ( AstraZeneca ).

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