Arguments for and against New Oral Anticoagulants

Safer than Warfarin but unavailability of antidotes leaves doctors in two minds

Dr. Rishi Sethi


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Dr.Kunal Jhaveri

A very known cardiologist from the City of Lucknow, Dr. Rishi Shettey who is currently associated as a professor of the Department of Cardiology from the King George Medical University from Lucknow. Sir, it is a warm welcome regarding this revolution talk on the role of NOACs in the stroke prevention atrial fibrillation. Sir it is already very in detail discussed that in various conferences and various even in the published data also that the NOACs are definitively effective and a little bit on the safer side as compared to the Warfarin when you are preventing a stroke in atrial fibrillation. Sir, you have a very vast experience regarding the use of NOACs in AF conditions. So what is your take on that. The NOACs are really doing the as compared to the Warfarin or the data may defer as compared with the Indian population.

Dr. Rishi Sethi

I believe that when we are talking about bleeding in relation to anticoagulants or anti platelets for that matter, we have to understand that if an agent becomes more potent either as an anti platelet agent or as an anti coagulant agent it will certainly cause more bleeding (01:00). That is a double edged sword and that is a trade off that you have to trade off between the thrombotic events and the bleeding events. When we are talking about NOACs causing less bleeding, what we mean to imply and we should train the physicians and tell the physicians specifically that they are causing lesser bleeding especially intracranial bleeding as compared to Warfarin and standard therapies because of the simple fact that NOACs are more specific inhibitors of coagulation pathways whereas Warfarin inhibits wide range of activities. So, when we talk about lesser bleeding, I believe one point that has to be emphasized again and again is that NOACs are causing lesser bleeding as compared to Warfarin and overall certainly if the agent is more potent it would cause slightly higher bleeding. When we use the term less bleeding we have to put this point also that it is causing less bleeding as compared to Warfarin. That is my point of view.

Dr.Kunal Jhaveri

So, I think it is very well said if it is more potent (02:00), then definitely effect is good, then there is more chance of side effects also as well. Related to this bleeding part, in Warfarin definitely you have to measure the INR because it is very variable when it is low, when it is high. So, measurement should be very regular and frequently and according to that you have to change the dose. Now the claim on this NOACs part is that, that this practical issue can be sorted out with the use of NOACs. There is no need of INR monitoring. So, what is your take on on this particular aspect.

Dr. Rishi Shethi

It is true that the advantage which some physicians perceive with the use of Warfarin is that you can actually measure INR, it gives you some sense of what the anti coagulation parameters are like and how much and people become very comfortable if the INR range is in the normal that they want it to be. But that is one thing. Another thing that has to be brought in this discussion is that Warfarin itself and INR therapeutic window is very narrow (03:00) and many a times all of us who have been measuring the INR with oral anti coagulations with Warfarin and the other older anti coagulants, we have found that the INR measurement is highly highly unreliable and the same patient over days and over same day can have various readings. So this false sense of security sometimes may be disastrous for the patient. As far as patients not being sure of anti coagulation profile on the newer oral anti coagulation, it is like, it is there all in the mind, I mean why do not we check anti platelet activity when we are giving aspirin or clopidogrel for sense. If the drug constantly proves over a period of time and in large multicentric trial that is having efficacious as far as the anti coagulation effect is concerned, I do not believe there is any rational of us trying to say that just because INR we cannot assess by easy methods the amount of anti coagulation we should not go forward and use it (04:00). It has been shown over the trial that even if we do not measure anti coagulation profile then too it works fine as far as the stroke prevention is concerned.

Dr.Kunal Jhaveri

Okay, so it is very well said that regarding your concern on INR. Now the third thing is that bleeding, definitely the Warfarin has a major side effect of bleeding especially with intracranial hemorrhage, but it is also said that they have the antidotes. So, I think even there is a belief that this drug can be, it is effective, but when it is going beyond the safety margin then we can have one arm in our hand to reverse the effect of a vitamin K antagonist. As of now, the NOACs the antidotes are not available in India. So, when the bleeding is happening with the NOACs, then what is your take on to manage this kind of condition.

Dr. Rishi Shethi

Too many skeptics, it would appear that not having an antidote is a serious handicap with the newer anti coagulants. So, firstly the antidotes are in the process of being discovered and tried in various. So we are having newer antidotes (05:00). Of course they are not yet available for wide spread clinical use and they are very expensive, but on the other hand if you just look at the clinical aspect and what are the clinical scenarios we are talking about, I mean many of these drugs are b.i.d. doses. So they are very short acting. So, even when the bleeding occurs and even when the catastrophic bleeding occurs, just stopping the drugs would you know kind of reverse the anti coagulation within 12 to 24 hours. So, it is only those bleedings that can really kill the patient within the first 12 to 24 hours that we are talking about and they are really limited. So, they are close bleeding, large intracranial hemorrhage but here again once large intracranial bleed has occurred, what antidote will probably bring it down. It is the management of stroke and management of hemorrhagic stroke that would take precedence and as it is if you stop the newer anti coagulants, the anti coagulation profile would improve within the next 12 to 48 hours and that should be it. So, stopping the medication probably should do the trick and in worst, worst case scenarios (06:00), the antidotes are really coming up and in few years we will see some antidotes for newer anti coagulants also.

Dr.Kunal Jhaveri

So, definitely we are also hoping for some recent antidotes, one is already approved in US FDA, the second one is under the trial, under phase II trial. So very soon they should be available in India also as well. So, I think now we every crisp but in detailed discussion regarding bleeding aspects when we are using the NOACs and Dr. Shethi has given a very very wide and experienced solution, when the bleeding is happening with the NOACs then what we can do, what is the INR concern regarding the NOACs as compared to the Warfarin. So I think it is very clinical reach kind of the discussion what we had as of now. So, I think with this note we are ending our discussion. So, thanks a lot Dr. Shethi for providing your valuable comments.