Activity Transcript

Deborah Siegal, MD, MSc, FRCPC: Hello, I'm Dr Deborah Siegal. I'm a hematologist in Ottawa, Ontario, Canada, and I'm an associate professor at the University of Ottawa and an associate scientist at the Ottawa Hospital Research Institute.

Welcome today to all of you, to this program entitled "Health Disparities in Diagnosis and Treatment of Patients with Thrombotic Conditions." I'm delighted to be joined by Dr Geoffrey Barnes, a cardiologist and vascular medicine specialist at the University of Michigan Health System in Ann Arbor, Michigan.

Welcome, Geoff.

Geoffrey D. Barnes, MD, MSc: Thanks so much for having me, Dr Siegal.

Deborah Siegal, MD: Today, we're going to be talking about our favorite topic, which is cardiovascular disease and its treatments, antithrombotic therapies, and also health disparities -- and to identify some of those important disparities in care and outcomes, and then how we can start addressing some of those in our own practices.

So we wanted to set the stage today by emphasizing how common and important cardiovascular diseases are. They are the leading cause of death and disability worldwide and in fact, 40 million prescriptions, possibly more, are written for oral anticoagulants annually in North America. And why this is really important is because these drugs are used to treat and prevent diseases like stroke, pulmonary embolism, deep vein thrombosis, and coronary artery disease, but bleeding is the major complication of anticoagulant treatment and up to 2% to 4% percent of people each year have a major bleeding episode.

So one of our important jobs is to minimize the complications of bleeding in our patient population and maybe, Geoff, you can talk a little bit about what are the important ways we're now doing this in the modern era of anticoagulation?

Dr Barnes: Thanks for that great question. Over the last decade or so, we've really transitioned from vitamin K antagonists (VKA) being the main oral anticoagulant therapy for these thrombotic conditions over to the direct oral anticoagulants (DOACs) and that's because the DOACs have important benefits.

They're much less likely to cause major bleeding and importantly, they're half as likely to cause intracranial hemorrhage, the most feared complication. But at the same time, there's a little bit of an increased risk of gastrointestinal (GI) bleeding with these drugs as compared to VKAs. So it's important for us to understand those differences and make sure that all patients have access to these drugs so that they can experience the benefits and fewer side effects.

Dr Siegal: I totally agree. Bleeding is the major complication and actually limits anticoagulant treatment. So part of the treatment of these conditions is in fact, reducing the chances of bleeding and then optimizing care for people who have bleeding complications. But I think it's also really important that we take a step back as we think about the optimal care of individualized patients.

We know that epidemiological data suggest that there are actually important differences in the risk of getting cardiovascular disease and in the response to treatment of different people based on characteristics like their sex or gender or perhaps, their ethnoracial background and this is actually quite important when treating individual patients in our clinic.

I just want to pause here for a minute to say that when we're talking about some of these differences, I think it's really important to define what we mean. And so when I use the term ethnoracial, what I really mean to say is to describe individuals who have different ancestral backgrounds.

So sometimes we use the word ethnicity, for example, to refer to people who have shared cultural aspects like diet or behavior or language or religion and race often is something that refers to a person's maybe physical characteristics, such as bone structure or skin, hair, or eye color.

And so when we combined the terms together, it really implies a shared genetic or ancestral background. So it's actually something to keep in mind because it's not always a term that we hear in our routine clinical practice and out there, but it is something important to keep in mind when we're talking about what treatments might be best for individual patients.

It's also, something that's important to mention that these definitions are not actually standardized around the world. So other people may have other definitions and view things or speak about things differently. But just to emphasize the point that there are important differences between people for all sorts of reasons and it's our job to really sort out what treatments are best for them.

Dr Barnes: That's a really great point. I think the other term that people maybe hear a lot and may not fully understand what it means is the term “social determinants of health.” Obviously, we realize that the treatments and the therapies that we as physicians and healthcare providers offer are critical for patients but there are other elements that really play into this and I'm just going to throw out a few of these here.

We know that income and social status are very important determinants of somebody's overall health and their access to the healthcare system. We know that employment status and the working conditions that people are in are also important conditions here, as are somebody's educational background, their overall literacy and their health literacy. How well do they understand what's happening? How well can they communicate with others? With healthcare providers?

Dr Siegal: And I really appreciate the opportunity to chat about these aspects of care because I think while we've established that cardiovascular conditions are common, we also want to think about how can we optimize care and identify where we can do a better job and in particular, we're talking about disparities here.

Dr Barnes: It's a really important element. The US Centers for Disease Control and Prevention (CDC): They have a definition of health disparities that they use. It says, "These are differences in health outcomes and their causes amongst groups of people."

As we think about health disparities, we have to understand maybe what's driving them? Often, but not always, these are related to structural or systemic biases that exist. So I think about structural issues of racism, of sexism, of ableism, of ageism, of heterosexism, and of socioeconomic status and all of these exist within our societies and they influence the way in which people experience healthcare, access healthcare and of course, then experience the outcomes related to their health status. And our goal, both as individual clinicians, and as a society, and as a profession at large, is really to achieve health equity -- to make sure that every person has the same access to the health outcomes and doing so, get access to the healthcare system in and of itself.

Dr Siegal: I totally agree. And maybe some important examples could be to identify where we know these disparities exist or differences exist. For example, when we're talking about venous thromboembolism, or VTE, we know that women actually have a higher incidence or higher risk of a first episode of VTE, but actually men have a higher risk of recurrent VTE. There are other examples as well.

There are lots of factors that contribute to this. Of course, some of them are related to biology and genetics, but others are related to the social factors or social determinants of health that you just discussed.

Dr Barnes: It's a really important topic because it's not just about venous thromboembolism, although that's going to be sort of a center point of our discussion here... We see these disparities in many different disease states and illnesses. Just as an example, if you think about something like diabetes, we know that there are huge disparities between different ethnoracial groups in how they get access to the diagnosis of diabetes and the treatment options. Whether they're getting older treatments or some of the newer agents that have come out. We see the same thing in certain kinds of cancer care, like breast cancer care. We even see it in the hospitalized setting. I'm thinking about things like pneumonia that's being treated in the hospital setting or the care of patients who have a stroke. We see these disparities across ethnoracial groups and across socioeconomic groups. So this isn't just focused on venous thromboembolism, but venous thromboembolism has disparities just like we see in these other areas and it's something that we need to be working towards, really addressing.

As I think about VTE, and Deb, you certainly know this as well as others from some of your research... There's kind of 3 different areas that I focus on. You mentioned the incidence or who's more likely to develop VTE and you mentioned that difference between men and women. We also see a very important ethnoracial difference. African Americans/Black are much more likely to develop venous thromboembolism than White individuals in the United States and that's an important distinction that we see.

However, when you look at recurrence, whether somebody has a second or a third event down the line, we don't see that same kind of big disparity between those ethnoracial groups, but you highlighted that we do see an important one across sex differences between male and female individuals.

Perhaps, even more importantly is the real consequence, the outcome of fatality and we know that African Americans/Black, again, face a higher risk of early mortality when they're diagnosed with a venous thromboembolic event, especially if they're of older age, say older than 65 years, as compared to other ethnoracial groups. And so we have to understand why these disparities exist and how we can start to dismantle some of the elements that are leading to them.

Dr Siegal: I agree. One of the good examples of those differences is whether or not certain people are more likely than others to get the treatments that they need. And of course, these are very complex issues, so we're not suggesting that there's a quick fix but starting out by having these discussions and understanding the differences can really help us go toward the next step of, like you had said, mitigating them or making sure that all people have equitable access to care and have optimal outcomes.

We know that, for example, in another patient population, patients with atrial fibrillation, that there are disparities in what type of people receive oral anticoagulant treatment. And in fact, in a large US Medicare claims database study, it was shown that women were less likely to start oral anticoagulants compared to men and that Black individuals were less likely to start oral anticoagulants compared to White individuals.

And we can see or think about the consequences of that type of disparity, where as those people may be at higher risk of having a stroke because they simply were not prescribed oral anticoagulation when they were eligible. It's also important to recognize that some people may not be offered the optimal treatment. For example, Black individuals in the same study were less likely to be prescribed a DOAC, which we just talked about as having all sorts of advantages and are, in fact, recommended by guideline organizations over vitamin K antagonists (VKAs) for people with atrial fibrillation.

So you can see here, people not accessing the best care can lead to poor outcomes and so understanding this is quite important in order to address it.

Dr Barnes: Deb, that data that you talked about which is so powerful from the atrial fibrillation literature, I think we see some similar things also when we look at venous thromboembolic populations. We've seen certain racial ethnic disparities in who's getting a direct oral anticoagulant use there with Black individuals being less likely than Whites, as well as less likely than Asian and Hispanic groups to be treated with a direct oral anticoagulant.

But we also see this across the socioeconomic span and so patients who are at lower income status are also less likely to be prescribed these drugs for many reasons that I think we all understand. They're more expensive and so they may be harder to afford and whatnot. And so we have to try and think about how do we make sure that all of our patients, whether it's across racial ethnic groups or whether it's across socioeconomic groups, get access to the level one guideline-recommended therapies so that they can experience both of the benefits but also not have to experience some of the side effects from older treatments.

I'm wondering if you could maybe walk us through a little bit of what some of the randomized trials have talked about. We've summarized a lot of the observational literature. Where do some of these disparities exist in the randomized trial populations that we've looked at?

Dr Siegal: Yes, very important aspect of care because our treatment recommendations, of course, come from randomized controlled trials, which evaluate the benefits and harms of treatments and establish the treatment preferences. What we do know is that in contemporary trials of anticoagulants, for example, for all sorts of treatment of all thrombotic conditions, including venous thromboembolism, for example, most clinical trials evaluating these therapies have enrolled very low numbers of individuals from non-White ethnoracial groups and so the majority of the data that we have for randomized control trials are from White individuals.

We also know that other important groups like women and the elderly are underrepresented in cardiovascular research in general and so these treatments have actually been trialed or tested in individuals of more homogeneous backgrounds than exist in the general population. And from these trials, we can also see that, although there's a small minority of people from non-White backgrounds, there may actually be differences in terms of the outcomes and we're talking about thrombosis or whether we're talking about thrombosis or we're talking about bleeding. And unfortunately, the numbers are just too small really for us to derive firm conclusions about that which makes us think that we need to improve our understanding of how these treatment affect a diverse population of patients because actually, those are the populations that we see in our clinic. Those are the people we treat.

And so, individualizing care optimally means understanding that there may be differences between groups, particularly with respect to bleeding risk, let's say -- in east Asian populations, we have seen in a number of clinical trials that the bleeding risks are increased and in fact, a number of clinical trials in anticoagulants have studied East Asian patients alone in that population because of this difference in underlying bleeding risk and perhaps that some dosing of anticoagulants could lead to more bleeding in people of East Asian descent than non-East Asian descent. And so that's an example of a place where I think we have actually some randomized trial data.

Dr Barnes: And we even have some understanding of maybe why that bleeding disparity exists. I'm certainly not suggesting we understand all of the mechanisms or reasons, but there are certain things about the East Asian populations that drive this. For instance, higher rates of H Pylori infection, being associated with GI bleeding if you're being treated with say, aspirin. Or a CYP450 variant that may change the way some of these drugs are metabolized. I'm thinking for instance, about CYP2C19 polymorphisms that are more prevalent in the East Asian populations, which really can change how responsive these patients are to clopidogrel, as an example.

We also know that there are higher rates of major bleeding and GI bleeding, even with our standard doses of direct oral anticoagulants, such that in many of these populations, the recommendation is actually to reduce the dose slightly. So they may have a standard dose in that population which is different than the standard dose we might use in a traditionally Black or White population. And so these differences are really important for us to understand at the time we're doing the randomized trials, so that then the broader populations can experience the benefits.

Dr Siegal: We've talked a little bit about differences that exist between people across groups with respect to the risk of these events, the management, and then the outcomes of these events. So where do we go from here? How is it that we work towards achieving equity for our patients?

Dr Barnes: I think it's a really great question and the honest truth is we need to work at multiple levels. There are things that we can do as individual healthcare clinicians to try and achieve health equity. But then there are other things, we're going to have to work at more regional or even societal levels. Obviously education is a big one. We need people to be aware that these health disparities exist. We need people to understand some of the mechanisms that drive them and to be empowered with the tools for how to specifically address them.

But I also think you raised a really good point, which is we need to make sure that our research is encompassing all populations. All populations of different racial ethnic backgrounds, of different sexes, of different ages. Often there have been groups that have been underrepresented so we don't understand the mechanisms by which they're going to experience good and bad outcomes with our therapy.

So our clinical trials and our observational studies need to be broader. And I know this is something you've written a little bit about, Deb, and I'm wondering if you could comment. How is it that we can actually incorporate the voices of some of these populations that may be underrepresented in the design of these trials and in some of our studies to make sure that they're more representative?

Dr Siegal: I totally agree. We have lots of discussions in the research community about building clinical trials and research platforms that are inclusive of people who have lived experience, or their caregiver’s, and to reflect their own experiences. So what we want to do is make sure that the research that we're doing resonates and is meaningful for the patients for whom it is supposed to be helping.

And so that's one thing, but it really does happen, I think, at a higher level, as you mentioned. So on an individual level, as a clinician or a researcher, this is a responsibility that I take on, but even other people, sponsors, funding agencies, health regulators, all these people really need to be involved to take steps to ensure that the research that we're generating includes underrepresented groups because those are the populations that we serve and that those clinical trial protocols reflect the patient's experience.

And I think in doing those things, we can start to understand how to better incorporate a diversity within our research platforms and it actually really will help us in the future to individualize treatment decisions for people who have different needs, different risks, different responses, to treatment, different values and preferences about treatment. Really that's the ultimate goal.

Dr Barnes: You talked about individualizing those treatment decisions, and I think that's a critical element, but we also need to, I think, marry that or merge that with care pathways that ensure all of our patients are getting access to the same types of care. We have these inherent biases, these unconscious biases that we all carry around, and we want to make sure that we're not letting those creep up to prevent somebody from getting a therapy which may be most appropriate for them.

So I think using these care pathways to ensure equitable access to therapy is important, but then, being aware of when we need to individualize that decision making so that it really can be the best choice for an individual patient. It's got to be an integration of both strategies together.

Dr Siegal: And I really like that way that you frame that because I think that leads really nicely into maybe an important thing that we don't always think about, which is advocating for policies that address disparities in care. And really here, we're talking about what we started about talking about which is the social determinants of health. So things that we aren't always thinking about as being directly related to health outcomes but that are hugely important. And so I think that really a comprehensive approach, including all of these elements, is what it's going to take. And these are by no means inclusive, but certainly some of these things are quite important for us to make some progress in this space.

With that, Dr Barnes, I'd like to thank you for this great discussion and thank the audience for participating in this activity. Please continue to answer the questions that follow and complete the evaluation.

This is a verbatim transcript and has not been copyedited.