Drugs in Atrial Fibrillation: Old and new

Vitamin K Antagonists have been the gold standard because of their efficacy, availability and cost effectiveness but the New Anticoagulants have a bright future
Dr. PB Jayagopal

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Dr.Kunal Jhaveri

We are going to discuss regarding atrial fibrillation. As you know sir, the atrial fibrillation is one of the commonest arrhythmic disorder even globally as well as in India, but if you find about incidence rate of atrial fibrillation it seems little bit to be unmatched as compared to the currently what the patients are coming in OPD and in your practice as well. So sir what is your take on this particular concern regarding the incidence of atrial fibrillation that whether the whatever currently reportedly globally it is approximately 2% whether it is actual or it may be under detected or what is the status in India, sir?

Dr. Jayagopal

Well, this is a disease mostly in the aging population, so though we have statistics from the western part of the world where it is close to about 1 to 2%, India, we really do not have a documented data about the incidence of atrial fibrillation. In fact we are actually looking into study from the cardiology society of India, Kerala chapter. 01:00 we are actually trying to start a registry also, but then the main problem is under diagnosis, I think it is underestimated. No doubt, I think particularly in Kerala, the health measures, the quality of life everything is better and so we have an aging population and definitely the incidence of atrial fibrillation will be on the rise. Therefore, I think we need some real registry data to back up on this and I am sure it is indeed a very huge population.

Dr.Kunal Jhaveri

So, definitely sir, you have raised a point regarding the aging population, as per one of the WHO survey by the 2040, the Indian population must be crossing almost around more than 35% when the age will be more than 65 years of age, so definitely this kind of disease where age is one of the important factor, we should have an earlier and on-time diagnosis before it is happening. 02:00 So regarding the screening part, what we are talking about screening part of atrial fibrillation, which is now getting very famous in western part of the world, so what is the current status in India and how we can improve in India as well?

Dr. Jayagopal

Well, if you look at the effluent population, no doubt I think most of the people would have a master checkup or let us say at least an EKG done, so that scenario, that subset of the population definitely would be diagnosed, but then the population at large when you talk about a country like India where you know the mass majority do not even have an access to primary health care, it is indeed difficult to screen them, but then I think over a period of time, for example, at least we have made tremendous progress in Kerala. I am certain that you know, most of the people whether they are rich or poor they at least from the cardiac perspective they get ample opportunities for detection and treatment. So I think in the overall context, I think over a period of time there has to be better screening methods, at least an EKG for someone above the age of 03:00 let us say, arbitrarily you keep a particular age, because we know for certain that above the age of 65 years this is indeed a major problem, so I think some screening methods will have to adopted for a better diagnosis of atrial fibrillation. One is this routine EKG can really pick it up, but then other thing is that I think tomorrow’s world, I am sure with the technology just creeping in, the smart phones have become the fashion of the day, so today, you know, it is not difficult at all for someone’s, let’s say, his oximetry or oxygen level or let’s say even his heart rhythm can be monitored and then everyone, rich or poor, has a mobile number, at least in Kerala I can tell you for certain we probably have the maximum number of, I think more than 120 billion users will be the projected figure. So if you have some access or some application where you can link it on to your mobile phone and EKG rhythm strip could be done, so atrial fibrillation could be easy to diagnose. I think there is a bright future from that front.04:00

Dr.Kunal Jhaveri

Definitely, it is very nice thought from your side that regarding we can have one center of the ECG database that from physicians you can collect ECG and they can send you on WhatsApp is one of best technology as well.

Dr. Jayagopal

No not even WhatsApp, I think from a patients perspective they can have an app which is downloaded. See, no one ever felt that WhatsApp could be so popular, today see even the least educated person gets used to using a WhatsApp, so I am sure this could be used for the help of the medical community at large.

Dr.Kunal Jhaveri

Definitely, regarding management part, if you talk about the atrial fibrillation, definitely rate and rhythm control remains the first priority to treat the atrial fibrillation, but if we talk about the complication of atrial fibrillation, as we know that when the patient has confirmed atrial fibrillation diagnosis then there is five times higher chance of risk of development of stroke. So regarding this particular stroke complication prevention, as of now the conventional management what we were using the aspirin or either oral anticoagulants 05:00 like the warfarin and other vitamin K antagonist, they are available since last almost more than 50 years world wide, so what is your clinical experience regarding this particular group of drugs?

Dr. Jayagopal

Well, it is the test of time, that the first thing that I want to convey and it is a cheap drug, both aspirin as well as warfarin, but then I really cannot give you the statistics where what percentage of patients with atrial fibrillation when they really deserve this molecule whether what percentage around this medications, but then overall I think we are all scared about the bleeding tendency with warfarin, so until and unless we have a proper laboratory measure to really have a very standardized blood test which is difficult in most of the centers, even in the best centers also, sometimes it is problem, so that is one of the major limitations and so mostly what happens in the Indian context, I think, the physicians tend to probably under correct the anticoagulant level so that you know you do not have the bad complication of a bleeding tendency, 06:00 so from that perspective I think may be most of these patients are under treated, but then I think overall if it is just a paroxysmal atrial fibrillation, I really do not think that you need so much of oral anticoagulants, you really have to decide clinically whether they merit an anticoagulant, but if they really merit an anticoagulant then I think warfarin is not a bad choice but then we all know the problems with warfarin.

Dr.Kunal Jhaveri

So sir, have you found any real kind of challenge with this kind of use of the drugs in AF patient that you have given the drugs to the patient and then maybe long term followup is not there and when the patient will come then INR level may be disrupted, so have you found this kind of challenges?

Dr. Jayagopal

This is a problem when you have a really very elderly patient where there is no one to take care of the patient and they cannot really schedule visit for frequent lab tests, those are the group of patients where you know you sometimes end up seeing them with a very high INR and they keep on taking this medicines and then of course 07:00 there are lot of other medicines they are on along with this medicine, so there maybe a drug interaction, so that is a problem I would say less than 5% in the population will have that, but most of them I think if you educate them properly they do come back for a blood test and then also I think the rapport with the treating doctor is very important that way.

Dr.Kunal Jhaveri

Definitely, regarding this challenge is there, but definitely proper awareness and counseling of patients definitely will help and reduce all the kind of challenges also very well. Now, if we talk about the newer generation or oral anticoagulants which has recently just within the last four or five years it has been launched in India as well, so what is your take on on this particular group of the drugs, where the rivaroxaban, dabigatran, and apixaban, now they are available in India and they have proven that they are at least non inferior to the VKAs and safer side as compared to the warfarin as well, so how do you opine on?

Dr. Jayagopal

Well, it is a welcome change, no doubt you know 08:00 because these molecules are perhaps the next generation agent which we use in sitting but then my experience has mostly been with dabigatran, so it is a good molecule, but then again we tend to be careful in patients, particularly elderly patients, patients who have some renal impairment, and all that, but then they have too many different dose scheduled available, so that is one of advantage of dabigatran and then maybe because that was the first molecule which came into India, so our experience definitely is much larger with that, but then it is a good molecule, we have had not major problems with that. Again, the advantage of not putting through somebody though all these frequent blood tests, but the main concern is the cost. So that is a major issue and we also have a policy in our hospital where you know apart from atrial fibrillation the other area where be use is for venous thromboembolism prophylaxis. So there also you know we tend to use this in a very sizable amount of patients. It is a good molecule. We have never had major problems, 09:00. Once or twice I had patients with Apixaban coming with bleeding tendency, but once they have bleeding problem, it perhaps is a little more difficult to control than, because now only the antidotes are just coming to the market, newer antibodies and all that. So that is a little more trickier situation because warfarin you know the way to counteract and the very predictable way to do it. So that is the only concern which I have. Of course rivaroxaban again just new to the Indian market and I am sure it should work the same way with. Personally I do not think there is anything to choose apart from the fact that the dabigatran is a problem. You read into literature you know I was scared when you have a patient with MI, chance of them getting a myocardial infarction but then the same thing was said about rosiglitazone. It went away from the market now it has come back again. So I think it is just probably early days to talk about all this.

Dr.Kunal Jhaveri

You have very well said that definitely MI is the part of some major concern with dabigatran but still it is nonsignificant so we cannot say anything about this particular side effects on this particular drug. 10:00 So sir just you said that the rivaroxaban, apixaban, dabigatran, all three are more or less equal, they do not have any head to head comparison as of now, but still if you have a choice to choose one agent in different groups, subgroup of patients, like renal failure, patients with prior history of MI, prior history of GI bleed, then in this different segmentation how will you place all the molecules?

Dr. Jayagopal

Well, in ACS situation I would definitely avoid dabigatran because with the kind of negative data that we have, that is one thing for sure, but apart from that I think the dabigatran is an advantage where you know you can even use it in a dosage of 75 mg twice daily in renal impaired patients. So there is an advantage like that but otherwise I think in a routine practice particularly for atrial fibrillation, really it does not make much of a difference.

Dr.Kunal Jhaveri

Sir, last question is regarding the stroke prevention in AF. It remains one of the lifelong therapy. So even the guidelines also suggest that once patient is diagnosed with AF then at least oral anticoagulant should be for lifetime to prevent a stroke 11:00 and we have the data regarding the Vitamin K antagonist that it is one of the poor compliable drugs that at the end of one year and second year globally only 24 to 30% of the patients remain on treatment and rest of the patients may have either interrupted or discontinued the treatment. So in compare of that compliance point of view, this rivaroxaban, dabigatran, and apixaban how will you prefer that?

Dr. Jayagopal

Let me put a counter question to you. Well, we have the problem even with a post ACS patient with just a simple aspirin and clopidogrel. People do not keep taking this. Aspirin is supposed to be life long and we find lot of people coming back without any medications or stopped medication. From that prospective, I think it is just the same. I mean, nobody wants drug to be taken for a longer time, but then warfarin apart from the kind of, if patient is stable, lets say somebody is stable on 5 mg of warfarin and they do well without much bleeding tendency then there is no major 12:00 scare for them and they would rather continue because it is a cheap molecule as such, but then the issue is once you have a negative effect because of that due to some bleeding tendency then they worried about it, otherwise all patients take it because they know for sure that if they have to have a good quality of life they need to have this molecule. So in that context I think warfarin or any other molecule just remains the same. The only difference I would feel is in terms of your INR monitoring. So the worry that you know this might just jump on to a higher level on a day and another day it would come down plus the food interaction. That is an area of major concern. Many people are really scared about finally what was said and the food intake is also very integral part of everyone’s life. So that is one challenging area and that is perhaps one area where the NOAC could probably replace, but I think the bottom line is the cost should come down. So it is prohibitively expensive these days. I think it has to come down. Then I am sure there is definitely a future for the newer oral anticoagulant agents.

Dr.Kunal Jhaveri

So definitely your messages sir well we have taken. 13:00 Now just in last we need some file important to take away so that we can discuss these points to the physician as well as the patient’s part that for atrial fibrillation and the stroke prevention in atrial fibrillation, what advise you want to give to the physician as well as the patients.

Dr. Jayagopal

First thing is you need to assess whether the patient really needs an oral anticoagulant. You know you have different criteria the CHADVASc score and so on and so forth, and if you are convinced that the score is there and then you need to put a patient on an oral anticoagulant that is the way to go about, we all know for sure and then you have the different choices. The advantage of this agent is that you know you have advantage where you do not have to monitor the blood test very frequently and renal impaired patients, in fact I was reading the literature these days. Warfarin is also known to impact the renal function over a period of time. So perhaps that point of view I think all of the newer agents are effective and dabigatran also in a renal impaired patient could be used at a lower doses and the newer molecules like rivaroxaban, apixaban 1400 again definitely has a place. There is no drug interaction, no food interaction, so that is I think one of the key thing that this could be used but then I think it is important that this is lifelong remedy and one has to really look into the financial status of the patient as well. One major area where I would feel this is useful is because when you start using an oral anticoagulant, particularly when there is a real indication you always overlap it with heparin or low molecular weight heparin, which is not required for this molecule, it starts acting straight away. So that is one major advantage for the physicians where they just start it as an outpatient basis, they can easily monitor the patient. But then a word of caution, because when these patients come to you with a bleeding tendency, you really have to tackle this because some of this are not really dialyzable but then sometimes you know you have to give a fresh frozen plasma and then really take care of this problem and then I think we still have to wait for the newer antidotes to come into the market for you to feel more comfortable about this. It is just as a monoclonal antibody has to really come into the market and should be easily available. 15:00 So it has definitely got a place I think perhaps the future is this but then I think industry also should see that the cost comes down and then it is patient friendly.

Dr.Kunal Jhaveri

So definitely sir has said very well that atrial fibrillation is a major concern of the society and its diagnosis and awareness is also one of the major part that we have to focus on that and regarding we talk about the management VKAs are still the goal standard because of good efficacy and at the cheaper they are available and the NOACs has a bright future as compared to the VKA but still apart from INR monitoring if companies are focusing on cost then definitely it could be a next future of this particular atrial fibrillation treatment. So sir thanks a lot on behalf of us and definitely we are thankful for your providing your time and your valuable opinions.