I'm Eric Prostowski, and welcome to another segment of EP on EP. It's a particular delight to be with Larry Jackson from Duke University, because he's been a colleague from one of my Dukie buddies for a number of years, and he's going to talk with us today about an extremely important subject that is really, I think, not known that much about by many people. He's an assistant professor at Duke University Medical Center. He's an electrophysiologist, but also quite involved in areas of research, and what we're going to discuss today with Larry is racial disparities in the treatment of non-valvular atrial fibrillation. So, Larry, welcome to the show. Well, good afternoon, Eric. Thank you for the invitation, and certainly appreciate all your guidance and counseling and mentorship over the years. I'm looking forward to the discussion. Sounds great. There's something I learned, and in fact, I learned it from you a while back. There's a thing called the double paradox. I sort of knew each part once you described it to me, but I never knew it as a double paradox. So, why don't we start the discussion with you educating our listeners on what that is? Sure, Eric. The double paradox is a term that was coined by Dawood Darbar, who does research in some of the genetic determinants of AFib as a function of race and ethnicity, and what it is is it's a twofold paradox in that African Americans tend to cluster more of the classic risk factors associated with atrial fibrillation, such as hypertension, such as LVH, such as obesity, such as heart failure, such as obstructive sleep apnea, but time and again, study after study, they have less incident and prevalent AFib compared to Caucasians. So that is the single, the first part of the paradox. The second part is, although that African Americans have less incident or prevalent AFib compared to Caucasians, they have significantly higher risk and rates of ischemic stroke and death. And so, I think the term in itself is something that's not necessarily new, but should be understood for our listening audience. It's not a single paradox, it's a double paradox, and I hope that folks understand that while the incidence is lower for African Americans compared to Caucasians, the hard major risk adjusted outcomes of stroke or death are higher compared to Caucasians. So let me tease out both parts of that and get your input, please, Larry. So the first part of that, is there anything about ancestry that plays into this? Can you give us some of your thoughts on why there is this, the first part, not the second part of the paradox? Yeah, the data is limited in that area, but there is some things, and specifically from Greg Marks' group at UCSF, and when we look at ancestral patterns, and some of this has been studied in a nice circulation paper from the mid-2000s, and looking at specific genetic arrays, and what they did was, they were able to quantify a specific dose of European ancestry in Blacks, and the more European ancestry that a Black person had in this study, the higher their risk was for AFib. So clearly there is something in the European milieu that may be deleterious, and then something in the Black or African ancestry milieu that may be protective. Do we know specifically what those gene-gene or gene-environment interactions are? To date, we do not, but this is certainly an area of active research for multiple groups across the country. So now that you've brought that up, I don't know this, so I'm going to ask you. Has the incidence and prevalence of AFib been looked into in African countries, where there may be a different ancestral pool versus, let's say, the United States or somewhere else in the Western Hemisphere? That would suggest you could tease some of that out. I don't know that area, though. Can you help us out there? Yeah. Once again, limited study, limited data. There is a study, and what they did was they were concerned about under-ascertainment or just possibly missing AFib because of the paroxysmal nature of it in patients of African ancestry, so in a mixed ancestral cohort, including Black Africans, all with implantable devices. So you could actually capture AFib. They looked at the incidence and prevalence of this, and once again, Eric, it was still lower in folks of African ancestry compared to those of European ancestry. So do we have data just in the African pool? We do not. We have mixed ancestral patterns, but from what we know, it is still less incident and less prevalent across both aspects of the transatlantic. So let's go to the second part then. What I don't know is, is it that once you identify a Black person with AFib, you've suggested that they have a higher risk of stroke. Is that true regardless of, I don't want to say a CHADS VASc score because that's too broad, but let's say if you took equal otherwise, you know, a White and a Black person with same age and they both have hypertension, let's say, will there still be, regardless of that, a higher risk or is it because of risk factors in general? Yeah, my understanding and my thinking, and some of this is still to be determined, is it's more of a risk factor assessment and lack thereof of risk factor modification. We know that Blacks in general have more ischemic strokes, non-AFib versus not. We know that 20% of ischemic strokes in the U.S. are due to non-valvular AFib, but I think the risk factor and risk factor modification part of it is to me the primary drive. So obviously the most important of all the risk factors as far as life and death is strokes. So there seems to be some issues regarding anticoagulation and types of anticoagulation and I know that intracerebral bleeds. Could you educate us on that area, please? Yeah, I think this is a very interesting area, one I am certainly dedicated to in my current career development award and subsequent K application. And what we see is that African Americans are significantly less likely to get the direct oral anticoagulants than Caucasians. We've documented this in the orbit registry of the DCRI, both iterations of that, and several other sort of Medicare and Medicare claims registries. And sort of why is that important? You know, Shin and colleagues in 2007 and Jack published a beautiful study looking at the risk of intracranial hemorrhage for patients on Warfarin with atrial fibrillation. And they looked at it as a function of race and ethnicity. And as we know, Eric, everybody has an increased risk of intracranial hemorrhage on Warfarin, whether that can be white, black, Asian, or Hispanic. But what we really didn't know to that study was, boy, that risk of intracranial hemorrhage is significantly higher in Asian, blacks, and Hispanics compared to Caucasians. I'm sorry, that's with Warfarin? That is with Warfarin. That's right. Okay, go ahead. And so with the advent of the direct oral anticoagulants, what do they do? They specifically lower the risk of intracranial hemorrhage. So it is the thinking of some of us who are in this line of research that, you know, these underrepresented racial and ethnic groups may preferentially benefit from the direct oral anticoagulant agents compared to Warfarin because of that decreased risk of intracranial hemorrhage. But the data is clear. African Americans and some studies, Hispanics are just less likely to get them than Caucasians. So as you know, we've talked about this over the years. It really, it just bothers me to the core as a physician that there would be any disparities in care because we take an oath to be a doctor and it's not a gender doctor. It's not a race doctor, right? It's a doctor. So it always really bothers me. But I know in some cases, some cultures, for example, don't like certain things. I remember when I, first time when I was in Asia lecturing, just the thought of an implantable device was some of the, some of the, I remember I was in Korea, somebody came in with a slow heart rate with symptoms and they said they refuse a device because they didn't want to, it's a foreign thing in their body. So I guess my question for you next, and I don't know if it's answerable, but you know more about this than most people. Is the disparity because they're not being offered appropriate therapy? Is the disparity because they're being offered if we can't afford it or do you get a feeling that maybe there's a sort of different view of different kinds of therapy? I think it's a great, great question, Eric, and we are actually currently interviewing both African-American and Caucasian patients to understand those facilitators and barriers to orantic coagulation use. Right now, my current career development award, and I think what you're going to see that it is a multifactorial issue in that there may be patient related issues that are preventing or in a coagulation uptake. There may be clinician or provider related issues that are preventing uptake, and there may be health system related issues that are preventing uptake. I think the challenge for researchers like myself are to sort of identify those core regions and themes and begin to develop interventions that can potentially remediate those disparities. So I don't disagree with you. I think all of those issues, costs, knowledge just about AFib and then the stroke prevention options, cultural differences are all at play. In my line of thinking, in my line of work, I want to be able to give a patient informed values so that they understand what type of decision they're making. I want them to make an informed values based decision about the risk and benefits of oral anticoagulation. If they accept therapy after understanding what it is, that is great. And if they refuse it and make an informed decision with that refusal, that's also okay. But I think this is all about empowering patients that they have the knowledge, they have the health literacy, they are able to communicate effectively with their clinicians to make a good informed decision. I think if we can do that in some of these racial and ethnic groups, the uptake of oral anticoagulation will increase. That's just what I hypothesize. Well, I think that's really good advice. So as a summary, let me ask you now, if you were giving a lecture and you were talking to a bunch of EP colleagues, would there be a message as far as when you're seeing patients of different races who have AFib, so documented, is there from where your research, even though it's not finished, like you said, you're just off and running. Should we be offering ablation earlier or not? Should we be making sure to press the point of a DOAC versus Warfarin because we have additional information saying there's a higher risk of an intracranial bleed? That's not something I've routinely told people. I've told people across the board there's less intracranial bleeding. So what's your final message for the listeners? How should we approach the discussion of AFib in that population? That's a great question. I think as clinicians, whether that be PAs or nurse practitioners or EPs or general cardiologists, we ourselves need to make sure that we are well-informed and have the expertise, including these various nuances of race and ethnicity to explain to our patients. I think in the best sense of what we call patient-centered care and shared decision making, us as the clinicians need to bring top-level expertise to the discussion. That is our job, and it is the job of the patient to bring his own values and preferences for medical care to the discussion so we can combine and make a shared decision. But if we as the clinician aren't offering that top-level expertise and don't understand some of these differences and disparities as a function of race, not only with oriented coagulation but with pharmacologic rhythm control, with procedural rhythm control, if we aren't offering this information to our patients, we will never be able to change these dynamics. So us as the clinicians need to be educated about some of these differences as a function of race and really be able to articulate that information to our patient population. So, Rory, thank you so much. What a great discussion. This is an area that is going to require a lot more research, and I'm delighted that somebody of your intellect and capabilities is undertaking it. I will look forward to your publications. And thank you for joining us on EP on EP Show, Larry. Well, thank you, Eric. I certainly appreciate the invite, and once again, thank you for your time. Thank you.

racial disparities

non-valvular atrial fibrillation

double paradox

genetic factors

direct oral anticoagulants