Anticoagulation in atrial fibrillation

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I'm Dhineli Perera, your host for this episode, and it's a pleasure to be speaking to Professor Richard Lindley. Richard is a Professor of geriatric medicine at Westmead Applied Research Centre and the Faculty of Medicine at the University of Sydney. Richard writes about the pros and cons of oral anticoagulation in non-valvular AF and the importance of sharing the decision-making with patients. Richard, welcome to the program.

It's nice to be able to discuss these issues.

Yeah, it is, definitely, especially when it's something that's so prevalent. So, speaking of which, Richard, let's kick off with your comments in the article around the prevalence of AF. Why is this increasing? I would have thought that the prevalence of high blood pressure and high cholesterol was increasing too, but you suggest otherwise.

Yes, AF is interesting because, of all the classical risk factors for stroke, AF is actually increasing globally. We've actually done extremely well controlling blood pressure, especially in places like Australia. And we're doing very well with controlling cholesterol, and Australia leads the world in reducing smoking with legislation. But AF is increasing, and it's interesting to speculate on why this is the case. It could be a very simple reason, is that we're so successful with interventional cardiology, and primary and secondary prevention, a lot more people are living older with diseased hearts. And diseased hearts are the ones that tend to get atrial fibrillation. So I think this is just a reflection of successful aging in the community.

Okay. So, just part of this aging process that we're obviously seeing with more and more of with an aging population.

Yeah. I think as people get older, their hearts are older and this is what's driving the atrial fibrillation. And it's quite interesting to see what's happening with stroke. And for ischaemic stroke, atrial fibrillation is now causing perhaps up to two-fifths of ischaemic stroke. This is a big change from a few decades ago when the strokes due to AF was a much smaller proportion. But as we've had success in reducing the other classical vascular risk factors, AF is becoming the predominant risk. And as a stroke doctor, I all too often see people coming into hospital with a major ischaemic stroke and they have been known to be in AF, and for whatever reason, they've just not been treated.

Okay. Well that actually leads me nicely into my next question. So, you've mentioned in your article that the 40% of ischaemic stroke is largely due to this large artery occlusion for patients who are in AF but not anticoagulated. What proportion of these patients do you think might be undiagnosed AF? Because as we know, people can be walking around in AF and feel perhaps nothing out of the ordinary.

Well, that's a very good question. I think that the honest answer is we don't exactly know.

Okay.

But it's going to be a large proportion of people. AF can be very asymptomatic. So opportunistic checking at general practices and taking action when atrial fibrillation is seen, I think is the most important thing. The amazing thing with anticoagulation for AF is there is substantial undertreatment, and undertreatment is far more common than over-treatment, which also exists.

Yes. So your article mentions that part of the challenge is that research suggests only about two-thirds of patients were willing to accept the guideline-recommended treatment. And this could be the answer to part of what you were saying in this undertreatment being so common. Why do you think this is the case? Do you think, perhaps, it's a poor understanding of what the risks and benefits are of anticoagulation?

You know, it's a complicated field. We're offering a treatment that's a prophylactic treatment, bit like a vaccination. But unlike vaccination, this treatment does have a risk, and it really just behooves us as doctors to make sure we have the right conversation with the patients. Now, research with patient preferences has identified that if there is a 1% absolute stroke reduction annually with stroke, with anticoagulation treatment, patients are usually willing to accept that despite the risks of bleeding. And it's also important to note that patients are frightened of stroke and doctors are frightened of bleeding. There needs to be a conversation to just... So both patient and doctor are comfortable with the decision.

And I must say, the alternatives to warfarin do help with this discussion. The number of times a patient has said to me, you know, "I'm willing to take any treatment, but I'm not having that warfarin, Doctor." So, having the direct oral anticoagulants now available, and we've got good experience of using these new drugs, I think that's very helpful in moving to correct the undertreatment issue in Australia.

And a lot of it comes to convenience, doesn't it, which you've also touched on in your article. And I think we, as health professionals, often forget how inconvenient medicines are until we ourselves have to take them. So what are some of the inconveniences with warfarin that is not seen, or not there when you're taking a direct oral anticoagulant?

Well, obviously the lack of a standardised dose is an issue. And that means you've got to have your regular blood tests. And we know that a substantial proportion of time, people are not in the ideal therapeutic range when they're on warfarin. So, the direct oral anticoagulants with a fixed-dose regime that may need to be altered with regards to age, renal function, and weight. But once you're on that regime, it's a much more stable regime, and people seem to accept that far more easily than the hassle of warfarin.

Okay. And so you think dosing is probably the most common, well, the most important convenience factor. Is there any others that are worth mentioning?

Well, patients like once-a-day treatment and some of the direct oral anticoagulants can offer that regime. It's an interesting observation that one of the advantages of warfarin, in retrospect, has been the fact that you can miss a dose of warfarin and you're not in trouble. If you're on a once-a-day direct oral anticoagulant and you miss a dose, you could be under-anticoagulated quite quickly. So, I think as we learn to transition to the new anticoagulants, we also start appreciating some of the advantages of warfarin that we may not have realised in the past.

That we overlooked. I guess one other thing to keep in mind is that warfarin has just such a plethora of drug interactions that you have to be constantly skirting around, whereas the direct oral anticoagulants have their share of it, but nowhere near to the level of warfarin. So that can make it a lot easier, especially when you're talking about patients that do have these multi comorbidities and lots of other drugs polypharmacy too.

Yes. Checking the interactions with warfarin is always a difficult issue. And there's the controversy about whether you have to adopt a very strict diet if you're on warfarin. So, all these issues are a hassle for patients. And I think that's one reason why we're having more success, I think, getting people to take the direct oral anticoagulants, such as apixaban, rivaroxaban and dabigatran.

And so when it comes to bleeding risk, Richard, we can't just lump all bleed risks together, can we? Can you tell us more about the risk of intracranial versus gastrointestinal bleed risks for both the direct oral anticoagulants and warfarin?

Well, the good news is the risk of intracranial bleeding is reduced with the direct oral anticoagulants compared to warfarin. And this is a substantial benefit, because once an anticoagulation haemorrhagic stroke has occurred, although there are treatments to reverse that bleeding, they're difficult and they're time-dependent, and the damage is already done. So, the primary prevention of those intracranial haemorrhages is really important by having the safer agent.

Conversely, there's an observed increase in gastrointestinal haemorrhages with the newer agents, some of the newer agents. But GI bleeding is less fatal, more easily managed, and so I think the substantial benefit of the new agents is the reduction in intracranial bleeding.

So I guess that's really important to explain to patients because a bleed is a bleed is a bleed to a lot of lay people, whereas we understand that intracranial bleeding is obviously a lot more serious than a gastrointestinal bleed. So that when people talk about bleed risk, separating the two is quite important, I think.

Now, moving onto the scoring system, Richard. There's the CHA₂DS₂-VA score has evolved over the years. In my short time of practicing, I think I've seen about three different versions of this over time. But it's looking quite good now. How well is this tool used to decide whether a patient needs anticoagulation or not?

Well, I think the short answer is that we probably don't use the tool very well, that's part of the problem. As a geriatrician, my life's a lot easier because people who are aged 65 to 74 years get one point anyway, and people over 75 years get two points under this system, and we generally recommending treatment in AF when you're scoring two points or more.

I think, far more important, is just to try and remember the key other risk factors that put up your risk of having a stroke. And those are the ones that will be fairly obvious: having a previous history of stroke or TIA, any vascular disease, diabetes, hypertension, or heart failure. Now, if people want to check the score before they initiate therapy, well, that's good, and I'm a great believer in being a computer-assisted doctor. Despite being a professor, I have no shame in taking out my iPhone on ward rounds and looking up medication on iMIMS, or some of the other apps that the health service provide me free. I look things up all the time. And I think as doctors, we've got computers in front of us and it's worth checking. And I think for something as serious as a long-term initiation and treatment of anticoagulation, checking things carefully at the very beginning is pretty good practice, I would say.

And coming back to what we spoke about earlier, would you say that patients that have some of the risk factors mentioned in this tool should be routinely screened for AF? Because we've talked about how asymptomatic they can be. So, for example, would you say someone with a history of, perhaps, heart failure and hypertension should be screened for AF maybe twice a year or so?

Well, I probably can't give you the exact data on screening, but I think the new technologies are amazing. There are mobile phone technologies that can now detect atrial fibrillation with a clever device. There are pharmacies that are able to check the cardiac rhythm. If you're seeing your regular specialistic, a cardiologist, you're often going to be getting a routine ECG. But what I was saying earlier, that the probably important thing is that if AF is detected, something must be done. And what we do know is that AF is commonly detected and nothing is done. So I think the screening question is still a great area for new research to get better screening, but opportunistically, yes, check that pulse, check the ECG, if there's any doubt. In my own clinic in geriatric medicine at Blacktown Hospital, I get an ECG done every so often when I'm detecting an irregular pulse in someone who was not known to be in AF. And you often find it's just frequent ectopics and you can relax, but it's so important to just identify the onset of atrial fibrillation or paroxysmal AF.

Okay, so moving on to some of the risk scores that predict bleeding in patients on anticoagulation. Why have they not been quite as useful as we had hoped? Do they still have a role? Do you still use them in practice?

No, I don't use them routinely in practice. I think that the problem we've found is that the scores that predicting bleeding are also the ones that identify people at higher risk of that ischaemic stroke. So, what's probably more important is that if someone has an obvious bleeding risk factor that is amenable to treatment, that that would be worth attending to.

For example, if you're seeing someone who's got bleeding haemorrhoids, getting those fixed with a surgeon before you initiate anticoagulation is a really good thing to do. If people are drinking alcohol excessively, trying to approach that issue before considering anticoagulation is important. But of course, the big risks that geriatricians fear is the risk of falls. Falls when you are anticoagulated can be really very serious. And it's hard to get the exact data in Australia, but there's probably several hundred fatal bleeding events in older people who have fallen over, hit their head, and they're on anticoagulants. So it's not a trivial risk, and these things need very careful judgment. And it's hard to improve a falls risk, but if there are things that you can do, you should be doing this as part of your assessment of whether you should be anticoagulating someone.

And if I'm not mistaken, I think NPS MedicineWise does run some online courses on falls risk assessments if there are listeners out there interested in looking into that further.

Richard, for the GPs who are trying to manage patients that see multiple specialists, what would you say is the best way to manage the need to be on both an antiplatelet and anticoagulation? I'm sure there's a lot of people out there that struggle to juggle the conflicting needs, and then the duration of therapy to be on the antiplatelet. What are your tips for GPs out there managing this?

I think my main tip would be to get an absolute time period for when the double antithrombotic is required, and to put a reminder in your notes to stop the antiplatelet agent as soon as possible. We know that anticoagulation and antiplatelet agents given together undoubtedly increase the bleeding risk, but that might be worthwhile for short-term treatment for particularly high-risk periods, for example, after cardiac stenting. But you really need very clear advice from the specialist who's advised the double antithrombotic regime, as when it can be downgraded to just the anticoagulants as soon as possible. And, you know, this is really important. We don't want to increase the number of iatrogenic bleeds.

And even if that means a phone call to the cardiac specialist, then so be it, right? Just to clarify that.

And, you know, yes. When your GPs are sending in a referral, a little sentence of, "I'd be grateful for your advice on when it's safe to stop the antiplatelet agent," is a very nice, not-so-subtle hint for the cardiologist or vascular interventionalist.

Yeah. So Richard, your article does touch on the importance of blood pressure management in AF patients. Can you talk a little bit more about this with us today?

Yeah, this is very important, actually. We always worry about bleeding risks with anticoagulants, and we worry about the dose of anticoagulants, and other factors. But one very simple thing is that if your blood pressure is well-controlled with low variability, that substantially reduces the intracranial haemorrhage risk. We saw this very nicely demonstrated in the UK BAFTA trial, when the risks of bleeds were pretty similar with aspirin and warfarin. And I think it just demonstrates that really good blood pressure control can really help reduce that intracranial haemorrhage risk.

Excellent. And lastly, Richard, what's your favorite strategy to get patient buy-in with anticoagulation? After all, there is really no point in prescribing it if they're not going to take it.

Well, I think reassuring them that we've got substantial data from the clinical trials, and also from real-life practice, that the new anticoagulants are really safe, are an improvement over warfarin, and, we've now got substantial experience in using these drugs. So yes, they are a bit more complicated than other medication, but it's worth taking these tablets regularly to prevent a nasty stroke in the future.

Absolutely. Well that's, unfortunately, all the time we've got for this episode. Thank you so much for joining us today, Richard.

And thank you for the opportunity.

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The views of the hosts and guests on the podcasts are their own, and may not represent Australian Prescriber or NPS MedicineWise. I'm Dhineli Perera, and thanks for joining us on the Australian Prescriber podcast.