Monograph: A physician’s guide to Atrial Fibrillation

Optimum Anticoagulation can minimize the risk of stroke by two-thirds or more

Dr. PC Manoria


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Dr.Kunal Jhaveri

Sir, before starting our discussion, can you highlight some important points in your written book on monograph on atrial fibrillation. What is the key message that you want to drive.

Dr. Manoria

This monograph is basically written to physicians so that they can understand atrial fibrillation, how to assess the ischemic risk, how to assess the bleeding risk, when to initiate the anticoagulants, when to use the newer anticoagulants, and there are many subset of atrial fibrillation, each subset is also highlighted, so it is a very compact book on atrial fibrillation and each chapter is decorated with highlights so that if you do not have time, you can just see the highlights and you will be aware of the key issues in atrial fibrillation.

Dr.Kunal Jhaveri

So definitely sir, atrial fibrillation as you rightly mentioned is one of the very critical disease, is the commonest arrhythmic disorder worldwide and you also mentioned that it is at (01:00) physician level to know about this disease is very very important because diagnosis at first point of contact for the patient definitely at the physician level, so in your practice have you found that this atrial fibrillation incidence is little bit under detected as per the actual incidence.

Dr. Manoria

If you have sustained atrial fibrillation, it will not be missed by any good physicians, but on many occasions atrial fibrillation is paroxysmal that may last for seconds, minutes, and some of these patient develop stroke. Previously when stroke used to be developed an echocardiogram was normal, no other tests showing any cause of atrial fibrillation, they were categorized as cryptogenic stroke, but now with prolonged monitoring we know that if you suppose monitor ECG for seven days or five days, many of the so called cryptogenic stroke are in realty paroxysmal atrial fibrillation and that has produced this stroke, so one of the test before we label any patient as cryptogenic (02:00) stroke is to have a prolonged monitoring of ECG and many times you can pickup that paroxysmal, because you cannot pickup, suppose somebody is with atrial fibrillation for two minutes and he reverses to sinus rhythm you may stroke, so that is the, but if it is sustained atrial fibrillation, it can be picked up very easily. ECG will show and anybody can diagnose. Then no issues.

Dr.Kunal Jhaveri

Sir, rightly mentioned, and you also mentioned that stroke is one of the major complication of atrial fibrillation. It remains four to five times higher chance of risk of a stroke when the patient has atrial fibrillation.

Dr. Manoria

No. It depends on the cause of atrial fibrillation. Suppose it is valvular atrial fibrillation, the risk of stroke is 17 times compared to non-valvular it is five times the normal individual. So, if you are having a valvular atrial fibrillation which is seen in 50% of the Indian atrial fibrillation, the stroke risk is very very high and optimum anticoagulation is mandatory. Whereas if it is non-valvular atrial fibrillation, which is a dominant scenario in the West and not in India, the (03:00) risk is five times.

Dr.Kunal Jhaveri

So regarding the prevention of a stroke in atrial fibrillation, so far there is anti-thrombotic treatment is available, anti-platelets, oral anticoagulants, so what is your experience as of now, usage of these kind of conventional oral anticoagulants and anti-platelets in stroke prevention.

Dr. Manoria

See, if you provide optimum anticoagulation, the risk of stroke can be minimized at least by two-third or more. The problem with atrial fibrillation is many physicians are scared of the bleeding complications of the anti-coagulants, but they should be well versed with the subject and then there will be no issue. For example, if you want to initiate an oral anti-coagulant, you have to calculate the ischemic risk, means what is the risk of stroke. The Chad Vas Score is superior compared to the conventional Chad Score because it is more sensitive, so all these scores are given in any book or on the net and it takes hardly (04:00) 30 seconds to score. If the score is high, high means if you have 0 Chad Vas Score, nothing is required, 1 preferably anti-coagulant, but 2 or above you have to use anti-coagulant. Before initiating anti-coagulant, you have to check the bleeding risk because anti-coagulants will be associated with bleeding. If they are not associated with bleeding, they are not anti-coagulant. So if the bleeding risk, again you can easily check by the HAS-BLED Score and it takes half to one minute, very simple score. If the bleeding risk is high which means this risk of HAS-BLED risk score is more than 3, it is high. Even if the risk is high, it does not mean you should not give anti-coagulant because the benefit is still more than the risk. Most of these patients will die of ischemic stroke rather than bleeding, but if you have a high bleeding risk, you have to take certain precautions. First is there are many reversible factors for the stroke risk as well as bleeding. You try to minimize hypertension, kidney function, obesity, so many factors. (05:00) So, minimize ischemic risks and bleeding risks and then initiate if you are using warfarin, say because the patient cannot afford, you have to keep the INR between 2 to 2.5 and you must teach the physician and also the patient that very vigilant should be kept on bleeding, so that you recognize bleeding at the earliest. The patient should also be told the key point. The physician should also know, so you should periodically check. Of course, INR has to be checked, but sometimes, the INR is so fluctuating even after checking because it is dependent on very virtually most of the food items, so the patient should also be told to pickup bleeding at the earliest and with newer anticoagulants the intracranial hemorrhage which is very disastrous is 50% decreased by all the new anti-coagulants. So if you have high bleeding risk and you want to use the choice will be newer anti-coagulants and among the newer anti-coagulants it is Apixaban which produces least bleeding provided cost is not an issue, so high bleeding is the first choice is (06:00) Apixaban. Warfarin is not the choice. It will be used if the patient cannot afford. Because warfarin the bleeding continues for a very long time. The advantage of this newer anti-coagulants, their action finishes so soon, half life most of them is very small, so few hours it will finish automatically and now we have antidotes, but the issue is you should try simultaneous to reduce the bleeding and the ischemic risk. Control his hypertension, control his weight, control his renal functions all these things matter.

Dr.Kunal Jhaveri

Definitely sir, you have mentioned very correctly that VKAs are older and standard drugs, but still they have some practical challenges like INR monitoring, food drug interaction, and thus the patient has a double-edged stroke kind of condition, high risk of stroke, and high risk of ICH and in place of that newer generation of oral anti-coagulants like Apixaban, Rivaroxaban, and Dabigatran they have a chance to replace these kind of treatment. So, sir what is your experience that of this all three NOACs, how can we can put individually in some group of the patients. (07:00).

Dr. Manoria

See, if your relation or friend is taking an anti-coagulant like warfarin, you will understand the limitation. What is the problem with warfarin, always you have to keep the eye in between 2 and 3. He is always walking on a tight rope trying to balance the efficacy and safety of the drug. Today his INR is safe point, he goes to a restaurant takes something, he drinks, food items, I think there is a big list of the drugs and drug-to-drug interaction, food-to-food and some many that despite all precautions the INR will fluctuate and the pharmacokinetics and pharmacodynamics of warfarin are highly unpredictable. Some dose in different individual will produce different effect, same dose in the same individual will produce different effect over different period of time, so the variable pharmacokinetics, the variable pharmacodynamics and narrow therapeutic range. If you cross the range above 3, bleeding, below 2 stroke, the third risk because of these dietic restrictions, the patient is in a real mess. If he goes for a party, he goes for marriage, he is all the time looking at what to eat, what not to eat, and despite that things change and then (08:00) the action of warfarin is so prolonged that once you bleed, particular intracranial, it is very unlikely that you will revive the problem, ooze continues for days and the misnomer is that warfarin can be antagonized by vitamin K. If you use vitamin K intravenously, it takes 10 to 12 hours to act. It is not that IV push and action starts and even with severe bleeding with warfarin, you have to use these recombinant factor VII or other thing. Warfarin bleeding can never been controlled in dangerous situation. Mild bleeding may stop, so warfarin has an antidote but it is overwhelming expressed that it has an antidote. It has an antidote where even after intravenous administration, it will take 12 hours. In 12 hours, the patient will be killed. Even if you will get blood, it is going to ooze, ooze continues,. Indians are more notorious for this bleeding. Of course cost of the warfarin is less. There is no doubt that these newer agents are very good. They are criticized, but if you look at what is the variable pharmacokinetics, the newer (09:00) have predictable pharmacokinetics. One of the most distressing thing for warfarin lifelong blood testing, go to a pathologist, go to a clinician, again go to a pathologist, and again go to a clinician. That is not there. The third thing is lot of dietic restrictions which are not there. Drug-to-food interactions are non-existent with new agents. Drug-to-drug interactions are very few, say antifungal agents, AIDS, Quinidine, Verapamil, amiodarone, but these drugs are not commonly taken, it is not like the antibiotic you will take. So, you should be aware of these interactions and the biggest advantage is this greatest sigh of relieve is that he has nothing to test throughout his life. Food restrictions are not there and the pharmacokinetics are so predictable, the onset is quick, the off set is quick, the therapeutic range is wide, so there is no doubt that these agents are superior and the limitations which are criticized, it has no antidote. Automatically the action weans off so quickly (10:00) and now you have antidote for Dabigatran already approved, antidote for the Rivaroxaban is going to be approved very soon, but these antidotes are more for fear of the physician or may be for some of the cardiologists, the action weans off, but still now you can use. Another thing which is criticized is that you do not have any validated test to measure the anticoagulant efficacy. The reality is that they do not require validification of their anticoagulant because the pharmacokinetics are preventive, but this does not mean they will never require. They require if you have renal function, if you are going for surgery, if you have already bled, so the physician must be well versed as to what precautions, your renal function is very important particularly if you are using dabigatran, 80% rivaroxaban 66%, and apixaban only 25%, so if you have bleeding problem, you have kidney problem apixaban is the drug and the misnomer for warfarin is warfarin the recent Canadian meta analysis of more than it, (11:00) warfarin is worst for stroke and worst for bleeding in renal failure. So the ACC has recommended Apixaban and not warfarin. The misnomer is warfarin is not excreted so kidney gets free, but the recent data suggests warfarin gets worse with kidney disease. If you have severe renal disease, we will not use warfarin, knowing that it is not excreted through the kidney. The Canadian data, we will use Apixaban. It is approved by FDA also, so that is the. If these agents are used with caution, the only limitation is financial constraint, but most of the young persons bear the financial constraints because they do not have to see what I am going to eat today, I have to go the pathologist, then again to the clinician and vice versa and whole time my mind may not bleed if I enjoy and so these are the biggest advantages.

Dr.Kunal Jhaveri

Definitely sir, you have rightly mentioned. This is just the last question for you sir. You have three NOACs, Apixaban, Rivaroxaban, and Dabigatran. You already mentioned dabigatran is certainly (12:00) useful in these, Apixaban is useful, apart from this any condition is coming like the patient is high risk of MI, the patient is compliance preference, so in such kind of conditions, means in various kinds of the cardiovascular conditions, how will you categorize this?

Dr. Manoria

See everything is very simple. There will never be head-to-head trials, so you will say Dabigatran is superior, what is the data. The data will never come, so selection of this agent is very simple. If you have a patient who has a high ischemic risk and a low bleeding risk when the ischemic Chad Score is high, bleeding risk is plus/minus you will use Dabigatran in higher dose. Because Dabigatran 150 mg has the greatest power of reducing stroke. So, high ischemic risk, low bleeding, Dabigatran 150 mg. If you have a high ischemic risk and high bleeding because the most of the bleeding risk and the ischemic risk factors are same, then we will use Apixaban. Because Apixaban, the bleeding risk is minimal. The efficacy is just like warfarin (13:00). Or if Apixaban is not available, you may use Dabigatran 110 mg. Dabigatran 110 mg stroke risk is same, bleeding is less. Suppose you have renal failure, obviously you are going to use Apixaban. If you have GI bleed, we will bank upon Apixaban. If you have MI is the pseudo risk actually the number of MI has never been, whole two or three MI were there, but the number of patients who develops intracerebral hemorrhage 50% of them are dead, so where is the question of MI. Some nominal numerical increase was there, but somebody and CAD is not a contraindication of this. If somebody is scared, he can use Apixaban. Rivaroxaban does not increase MI. If your bleeding risk is very high CHAD score 3, 4, 5, Rivaroxaban has been tested in that patient. Elderly, Apixaban because they are bleeding prone, they have renal failure, so this is how it can be easily selected, although there are no head-to-head, but this is a very rationale and a logical conclusion which you can draw (14:00). Suppose my patient comes with severe renal failure, I am not going to use Dabigatran, I am not going to use, I will straight off use Apixaban. If the patient has high bleeding, high ischemia, I will use Apixaban. Even in absence of head to head trial, you can easily choose the agent and you can also reply why I am choosing it. It is not that elderly, I will Apixaban, I will not use.

Dr.Kunal Jhaveri

Yes, obviously. It is not hypothetical, but it is a very rationale.

Dr. Manoria

We have the data, why using Apixaban because the bleeding is risk, GI bleed, why using Apixaban, Dabigatran increases the GI bleeding so that is why I am using and then GI bleed is easily manageable for all practical purposes. Unlike the head bleed intracranial, you will die. So, disadvantage with Dabigatran and Rivaroxaban, they increased GI, but Apixaban does not increase. To some extent it may decrease it.

Dr.Kunal Jhaveri

So, definitely, as Dr. Manoria has said very well that he has given very practical kind of the approach as to how the VKAs are available, but they have very wide kind of practical issues like monitoring of INR, PT monitoring, food drug interaction (15:00) and poor compliance and the NOACs can replace that and even out of all three NOACs how each and every NOAC can be selected for single individual kind of patient, renal failure, high GI bleed and MI patients, so it is very well answered by Dr. Manoria.

Dr. Manoria

The only thing when should we use warfarin. Now, warfarin has to be used if you have a valvular atrial fibrillation. The newer agents are not suitable at the moment. If the patient is very poor, you will have to use warfarin. If some patient is doing well with warfarin, suppose his INR is stable, no ischemic risk no bleeding, you may continue at risk, but keeping in mind that the intracranial bleeding is 50% more with warfarin. If the patient and physician interacts and then decide that this patient whose is very well controlled, wants to shift to newer agent because of fear of intracranial bleed and that will finish if your bleeding risk is high due to some reaction, then even if the patient is doing good, we will shift to a newer agent or (16:00) you have a high risk of intracranial like hypertensive patient and atrial fibrillation, we will not prefer warfarin at all. We will explain because hypertension otherwise bleed, we will use warfarin they will, so high intracranial risk bleeders warfarin is not to be preferred.

Dr.Kunal Jhaveri

Also this is a well taken point that in which conditions the warfarin also can be used. Definitely it is very low cost available molecule and it has the own advantage in valvular conditions and as a part. So, thanks a lot Dr. Manoria for providing us your valuable time.