Thank you so much. My husband explicitly told me not to talk to people about my aquarium, but he's not here, so I had to throw that in. So the prompt I was given today is to talk about, I love the title, Across the Pond. So bridging and bringing together the differences between the AFib approaches between America and the European Union. And throughout this presentation, you're going to see a lot of really nuanced differences, but things that are substantial. Let me see if I can get this to work too. Oh, down. I'm not cool enough to have any financial interest at this time. All right. So why are you guys here today? I have a couple of objectives for you. First, we're going to be comparing and contrasting the European and American guidelines. There are going to be a couple of key points we're going to really be talking about. Things like the relevance of the term valvular, strategies in patients with AFib and CAD, the role of aspirin in AFib, and then differences between rate control targets. And then at the end of the day, obviously the goal is hopefully you can look at the data behind these differences and develop best strategies for your patients. List of abbreviations. All right. So this is the meat of what we're going to be talking about today. So on the USA side, we have the CORE 2014 AHA, ACC, HRS guideline with an update in 2019. And on the EU side, we have the 2020 ESC guideline. Now, I'm a very visual person. So if at any point you want to follow along, these are the QR codes to the guidelines. As long as you just don't scroll with your eyes closed, pick something, and ask me about it. I'm just kidding. All right. So let's put on our boxing gloves and see what each society has. So as we all know, AFib is a very common disease state. And you can easily spend an entire afternoon going through all these guidelines, looking at these nuances. And of course, we have a short time together today. So we're really going to be focusing on that 10,000-foot view today. When you're looking at these different guidelines, there's a ton of little nuances between these different societies. We won't have time to discuss all of them today. But here are just some things that differ between these guidelines. I do want you to know that although I will not be talking about them today, I have summarized all these differences for you in the appendix slides with tables. So if you ever were curious to see what the differences between these guidelines are, you can reference it there. So we're going to get started with terminology. Valvular, non-valvular. So I also kind of like history. So when we're looking at the history of the term valvular, it's in the 1970s where we see this term come up for the first time, valvular atrial fibrillation. And I'm sure to everyone's chagrin, no guidelines talk about what that term means. And it really wasn't until 2012 when the ESC guidelines came out and started defining what they meant by valvular. And in 2014, the Americans followed suit. But one thing I want to point out is even from the beginning, you can see discordance between what is meant by valvular a-fib. So these definitions are already different depending on what guideline you look at. Where are we at with this term today? Well, the Americans kind of whittled away a little. And now valvular a-fib is defined by moderate to severe mitral stenosis. Now of any etiology, so prior it was rheumatic, but now it's any etiology. And also the presence of mechanical heart valves. But in 2020, the ESC took a different approach. And they say, these terms are confusing. Let's not use them. I want to talk about why. So when you're thinking about what we mean by valvular a-fib, again, if you remember, moderate to severe mitral stenosis or mechanical heart valves. What is not included in that term? Bioprosthetic valves. So by definition, valvular a-fib does not include bioprosthetic valves. And when we're looking at the landmark anticoagulation trials of these DOACs in quote unquote non-valvular a-fib, when we actually look at the data, two of those four trials completely excluded patients with a history of bioprosthetic valves. And then the other two studies had less than 1% of patients enrolled with a history of bioprosthetic valve. So already, we're using these terms, but the data isn't necessarily representing all of these patients. Now since then, Dabigatran had a very small study. And by small, I say, I think there was an N of 27 patients, a pilot study. And they found that, you know, it's a small study, but the risks is similar to warfarin in patients with a history of bioprosthetic valve. It wasn't until this trial came out, the RIVR trial, where they looked at RIVROXABAN specifically in a-fib, in patients with a bioprosthetic mitral valve, which as you probably recall, is the more thrombotic position versus aortic. So this was a large RCT, and they found for the first time that in patients with a-fib and a bioprosthetic mitral valve, RIVROXABAN was non-inferior to warfarin with the respect of the primary endpoint, which included all the things we care about, major death, major cardiovascular events, or major bleeding. Now, the whole reason I'm talking about this is whether you choose to use the word valvular, non-valvular, moving forward, I think it's important to understand where there are limitations in that term, and where the data is. And, you know, being very specific with the patient that you're talking about and the patient in front of you, and how the data reflects them. All right, next we're going to talk about a-fib and patients that have CAD. Very, very common. So when I think about a-fib and CAD, there's already all the thoughts swirling in my brain, right? Do we do triple therapy, dual therapy? How long do we do this? Does stent type matter? All the different questions. When we're looking at these patients, there are some differences between the two societies. So in stable CAD, the Americans have no recommendation. ESC for the first time is endorsing an OAC monotherapy. In patients with elective PCI, so again, no recommendation from the Americans, but ESC is recommending a Class I triple therapy, so anticoagulation plus dual antiplatelet therapy, for less than or equal to one week, with dual therapy for six months. Moving on to ACS with PCI, well, the American guidelines now have something to say, but they do say if you do do triple therapy, you can transition at four to six weeks. So again, not that strong language. ESC recommends triple therapy again for that less than or equal to one week mark, with dual therapy at 12 months. And then ACS without PCI, to my knowledge, neither of the societies have commented on this yet. As far as the use of DOACs, I just want you to be aware, if you look at the American guidelines, you'll notice that not all the DOACs are included. So things like Apixaban, for example, and a lot of that is just due to the time that these guidelines were published. So the landmark trial that looked at Apixaban in patients with AFib and CAD, Augustus, that was probably not included in this, whereas ESC has that blanket statement, we prefer DOACs over Warfarin. And then as far as P2Y12 inhibitor preference, really both societies are mostly going towards Clopidogrel, likely because that's what we saw in most of the trials and it's associated with the lowest bleeding risk. So I wanted to briefly talk about this stable CAD recommendation because it is new and the American guidelines haven't had a strong recommendation yet. So ESC recommends OAC therapy, and that's due to this trial. All the cardiology trials have cool names, so this is a fire. It was a randomized control trial, large, so over 2,000 patients, follow-up of 24 months in patients with stable CAD. So they defined stable CAD as patients that had PCI or CABG greater than or equal to a year before. And they looked at rivaroxaban monotherapy versus rivaroxaban plus antiplatelet therapy. And when we look at the all-cause mortality, MI stroke, all these things for the primary outpoint, they found non-inferiority with rivaroxaban monotherapy, but they found a significant decrease in major ISTH bleeding. Now as far as duration, so if you recall, there are kind of differences between what duration these societies are recommending. These are all the landmark trials that assess triple therapy versus dual therapy in these patients with AFib and CAD. And a common theme of all these trials is that OAC plus P2Y12 inhibitor had less bleeding than triple therapy. And all of these trials use triple therapy until randomization, and then anywhere from one to two weeks after PCI. So when we're talking about ESC and their recommendation for that one-week cutoff, this is really where they're getting that data from. All these trials, like I kind of alluded to before, 90% of patients were on clopidogrel and the OACs were found to be favorable. So that's ESC standpoint. You might be wondering, well, where did AHA get the four to six weeks? So that is just based on the historical knowledge that when you're getting a stent, the highest risk of in-stent thrombosis is in that first four to six weeks. And again, remember that AHA doesn't have a very strong recommendation. They just say if you do choose to do triple therapy, you can consider switching at four to six weeks. Next we're gonna talk about rate control. So as we all know, AFib is such a common disease state, but when we're talking about rate control and what targets we actually wanna really get to, there's actually not a ton of good literature out there. And we have some discordance in what we should do among these societies. So the American Guidelines recommend a more strict rate control strategy, less than 80 beats per minute, kind of as their first line. Whereas ESC endorses a resting heart rate of less than 110 as their primary recommendation. Not the topic of today's discussion, but our Canadians, our neighbors to the north, they use the less than 100 as their first line recommendation. So more along the line of ESC. The thing that I love about this is that these different societies are using the same trials to make different recommendations. So the main trial that is discussed is the RACE-2 trial. So this was a randomized control trial of 600-ish patients with a follow-up of three years. They looked at lenient versus strict rate control. And again, all the good things for the primary endpoint, CV mortality, stroke, all those things. And they found that lenient rate control was actually non-inferior. A couple of things to note about this trial. So as you may expect, the target heart rate was achieved much, much significantly higher in those with lenient rate control. But not only that, patients that had lenient rate control required nine times less visits on average compared to those that had strict rate control. And when we're looking at things like adverse effects versus fatigue, there's really no difference found in this trial. But there are cons as well. So it was a single randomized control trial. And I'm sorry for my pediatric colleagues, but 600 is still not that huge in the adult cardiology world, so it's smaller for us. And we had a really low percent of patients that had a low reduced ejection fraction. So to summarize, again, same trial. But ESC is recommending pretty much, regardless of heart failure status, with the exception of tachycardia-induced cardiomyopathy, you can opt for this lenient control. Whereas AHA does still have a higher recommendation for that less than 80, although they also recognize, as we all do, I think, that the degree of rate control is still an area of uncertainty and controversy, and we need more studies. And lastly, we're gonna end with the role of aspirin. So this is where a more stark difference is present between the guidelines. So as you may recall, the American Guidelines, there is still a role, a recommendation, that you can consider using aspirin. The CHADS-VASc has to be low enough, and you can either opt to do aspirin therapy or no anticoagulation therapy, or antithrombotic therapy. Whereas ESC, and I believe the Canadian Guidelines as well, are actually having a class three recommendation that you should not use antiplatelet agents in AFib. Let's talk about the data. So there are a couple of trials throughout the years looking at the role of antiplatelet agents in AFib. We had the ACTIV-W trial back in 2006, and we looked at dual antiplatelet therapy versus warfarin in these patients. And we found that not only was dual antiplatelet therapy less effective for things like preventing thromboembolism, but there was a similar rate of bleeding. So this trial was actually cut off and stopped early because of harm. Then in 2009, we had the ACTIV-A trial looking at dual antiplatelet therapy versus aspirin alone, but that was in patients that were not suitable for warfarin or vitamin K antagonist. And maybe to no one's surprise, we found that dual antiplatelet therapy had a significantly higher rate of major bleeding. Then there was this trial in 2013. It was a retrospective trial, but it was a large national patient registry with over 100,000 patients. And they found that aspirin monotherapy had no reduction in ischemic stroke or thromboembolic event versus being on nothing. And then lastly, this other trial in 2007, this was more in a geriatric patient population, the BAFTA trial. So they looked at warfarin versus aspirin in patients greater than 75 years old, about 1,000 patients. And they found that aspirin was significantly worse as far as clinical significant arterio-thromboembolism. So even though a lot of the data kind of goes towards maybe not using aspirin in therapy, AHA still does recognize that there's not a ton of data on this. There's not a lot of large randomized controlled trials on this. And they do recognize that platelet inhibitors, whether alone or in combination, are less effective than warfarin. But they state that they may be better tolerated with some patients. And the term that we all love, you have to really balance the risks and benefits of bleeding in each of your individual patients. Thank you so much for your time today.

atrial fibrillation

AFib treatment

guidelines

coronary artery disease

rate control targets