Prof. John Eikelboom: I think if we put the next slide up and consider the appropriate use of NOACs. There is a summary slide here and listed are the current state of the art or suggestion of the current state of the art choice of anticoagulant. Choice of anticoagulant for different indications from VTE prevention treatment, VTE cancer treatment and atrial fibrillation. Then I have listed the preferred options, the reason why they may be preferred and the potential alternatives. If we look down the list for the preferred options I am suggesting it is NOAC, NOAC, NOAC, NOAC and maybe where NOACs have not yet been tested I put low molecular weight heparin, but it is becoming a NOAC dominant choice of anticoagulant.

Prof. Saskia Middeldorp: The reason is mainly convenience and safety. That is basically.

Prof. John Eikelboom: That is a fair point. I think if we take the atrial fibrillation trial however and think about what they were designed for, non-inferiority. In several cases there was actually superiority and if you think of dabigatran–

Prof. Saskia Middeldorp: Which is a massive surprise given that warfarin, if given well, is quite effective for a drug in general.

Prof. John Eikelboom: Yes indeed, I mean warfarin is dramatically effective in atrial fibrillation, there is a two-thirds reduction in stroke and 25-percent reduction in mortality. There are not too many drugs that achieve such big benefits.

Prof. Saskia Middeldorp: On top of that.

Prof. John Eikelboom: To get a further one-third reduction in stroke and when you translate that across a population of thousands, in fact on the world population, millions of people with atrial fibrillation, we are taking a lot of strokes prevented. There is, at least in that setting, a clear efficacy advantage particularly with dabigatran 150 and apixaban also has an efficacy advantage. Safety, you are right, safety is where everybody resonates with everybody that less intracranial hemorrhage and that translates into a favorable estimate for mortality. There is a lower-case fatality after bleeding, that is all very favorable and then getting away from the need for the rest of your life in atrial fibrillation having monthly blood tests, that is huge.

Dr. Hanna Pohjantähti-Maaroos: We have to remind the audience that we still need warfarin in some cases, especially in patients with moderate to severe mitral stenosis and in patients with mechanical heart valves, warfarin is the drug of choice.

Prof. John Eikelboom: To be fair to the audience, there are people here who use acenocoumarol so they are saying we do not need warfarin anyway or phenprocoumon, but I think–

Prof. Saskia Middeldorp: I think the audience is well educated and they know that we mean vitamin K antagonist in general. Yeah, I think we still need to stress the groups you just mentioned. For instance, pregnant women for VTE they cannot use NOACs. End-stage renal failure, so there will always be groups that at present will not be able to take NOACs.

Prof. John Eikelboom: Drug interactions, there are selected drug interactions where warfarin still.

Prof. Saskia Middeldorp: Yeah, so how do you handle–I think they are on your next slide, all those limitations, aren't they?

Prof. John Eikelboom: I think we have some of the issues related to NOACs management, and some have said these agents are not fire and forget and I like that phrase because NOACs are really so simple to treat. To use. They are effective and they are safe, gives a sense of, well prescribe this stuff, you are out of my office and I forget about you, but that certainly is not the case because they are still anticoagulants, they do still confer a risk of bleeding and we need to review these patients for a whole range of reasons. Listed here on the slide, but amongst them we need to ensure they are on the right dose, because there is a tendency to under dose and patients themselves sometimes drop a dose. They say, if this is good for me maybe half is also good for me. We need to make sure they stay on the treatment, they adhere to the treatment regimen, we need to watch their kidney function, and make sure that they are not starting to take some drug that interferes with their NOAC. I would strongly advocate that we see everybody at least once a year and if they have renal impairment we are gonna see them twice a year or sometimes three times a year. In the worst kidney function we may see them every two months.

Prof. Saskia Middeldorp: Yeah, I think that if we look at adherence I know you have done quite some work on it. We know for antihypertensives, statins is really poor. Of course, we try to increase it by having nurses or dedicated clinics. Do you always keep the patients in the hospital, I know that systems change or vary substantially between countries, how do you make sure they adhere particularly if it is primary prevention of stroke?

Prof. John Eikelboom: I think this is the elephant in the room. We can have the fanciest, the best drugs, the reversible drugs, the simple drugs, but if people do not take them they cannot benefit. I think the biggest challenge we face as clinicians is closing that adherence and persistence gap. Part of that I think is early careful education, part of that is careful follow up. We started from following all the NOAC patients, but to be honest we are overwhelmed. Now it is being pushed out to the responsibility of the family physicians, in fact they are stepping up to the plate and doing a very good job, but these patients need to be seen regularly by the family physicians to ensure adherence.

Prof. Saskia Middeldorp: How is that in Finland?

Dr. Hanna Pohjantähti-Maaroos: In Finland there are educated nurses in the healthcare centers that are educated to follow up anticoagulated patients and they consult their doctor if they have some problems. I think that the most important thing to keep the patient adherent to their treatment is to inform the patient why the medication is used, what is the risk if they stop using it, and even to take the patient to take part in the decision making which anticoagulant–

Prof. John Eikelboom: Right.

Dr. Hanna Pohjantähti-Maaroos: –and also to keep them on follow up regularly.

Prof. John Eikelboom: I think engaging the patient is incredibly important, nowhere as important I think as in anticoagulant therapy. They need to know why they are taking it, they need to know the hazards, and they need to know the importance of persisting despite the hazard.

Prof. Saskia Middeldorp: Yes exactly, I think it is a matter of where you work and how your healthcare system is being organized how to do that. As long as you make sure that someone is doing it and you are not thinking that somebody is doing it. In the Netherlands we have the anticoagulation clinic, they were all designed for INR control and some of those are now changing gears, but general practitioners are taking over cardiovascular risk management with educated nurse practitioners as well. The complicated ones stay in hospital and let us say more straight forward patients they are very well off in a less academic environment or less hospital-based environment, and I think it is going quite well. Do you have any specific remark that you did not have the chance to make?

Prof. John Eikelboom: All we can say is we are very grateful to live in an era where we have such important advances for patients in anticoagulant therapy and I think the NOACs, the DOACs have been an incredible advance. Now supplemented by reversal, it has sort of turned the full circle of complete coagulation control which I think is an incredible advance for patients.

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