Monday, August 31, 2009


Warfarin is a very old drug, almost as old as myself. It was approved for use in 1950 in the US for the treatment of Deep Venous Thrombosis ( DVT ) other forms of peripheral vascular thromboembolism, use following artificial valve rerplacements and also in atrial fibrillation. For the many good that it does, there are also many problems, primary of which is bleeding. Warfarin is a very fussy drug and has a low therapeutic index. It is affected by many foodstuff, making its use and control difficult. Patient have to undergo routine blood test, so that as clinicians we can guage its strength and so prescribe a correct dose. With too hign a dose, we of bleeding and with too low a dose, we run the risk of thrombosis ( clot formation ). It also takes a fews days for its action to come on.
Yesterday ( 30th Aug ) at the European Society of Cardiology Congress, now going on in Barcelona ( A H1N1 or not ), Dr Micheal Ezekowitz presentaed a paper entitled " Randomised Evaluation of Long-Term Anticoagulation Therapy" or Re-Ly for short. This is a study comparing the use of a new drug called Dabigatran Etexilate ( Boerhingher I ) versus Warfarin in the management of chronic atrial fibrillation. It came out that Dabigatran E at either 110mg BD or 150mg BD is better then warfarin. 951 centers in 44 countries enrolled 18,113 patients. So this is a very large study. There was a 35% reduction in in peripheral embolism and strokes, and a 74% reduction in bleeding . However, it is important to note that this is not a blinded study. It is what we call an open probe design, meaning that the investigators and patients know who is taking what, thus giving us a potential possibility of biaseness and error. Be that as it may, the results are also encouraging. There are however two notes of caution. Firstly, the mean followup period is two years. There is a slightly increase ( though not significant ) in Myocardial Infarction rates. and also the previous member of this group of drug, ximelgatran, had a nasty, serious side effects of liver necrosis. Perhaps we have to observe longer. Dabigatran is an anti-thrombin, which means that it binds to the thrombin and prevents it from cleaving off to trigger the clotting cascade. It is an anticoagulant and so the slight increase in heart attack rates must be carefully observed. It would appear that in some patients instead of blocking, it may infact stimulate the cascade. I suppose there is no perfect drug. However, we are assured that after two years, the rate of that happening is rare.
Well, on the positive note, there looks like a possible alternative to the " rat poison " warfarin that we now prescribe to our patients. The last note to observe with these new designer drugs is that it cannot be cheap. Warfarin on the other hand is dirt-cheap.


No comments: