Assessment and Treatment of Cardiovascular Risk Factors in Veterans with Prostate Cancer - Ravi Parikh and Lova Sun

May 12, 2021

Cardiovascular disease is a leading cause of mortality in patients with prostate cancer, and androgen deprivation therapy (ADT) may worsen cardiovascular risk. Adherence to guideline-recommended assessment and management of cardiovascular risk factors (CVRFs) in patients initiating ADT is not understood.  A recently published study that describes CVRF assessment and management in Veterans with prostate cancer initiating ADT and overall is the topic of this discussion. Ravi Parikh, MD, MPP, FACP, and Lova Sun, MD, join Alicia Morgans, MD, MPH to discuss the recently published study in JAMA Network Open, "Assessment and Management of Cardiovascular Risk Factors Among US Veterans With Prostate Cancer the US."


Ravi Parikh, MD, MPP, FACP, Assistant Professor, Department of Medical Ethics and Health Policy and Medicine, Perelman School of Medicine, University of Pennsylvania, Staff Physician, Corporal Micheal J. Crescenz VA Medical Center, Philadelphia, PA

Lova Sun, MD, Fellow, Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

Read the Full Video Transcript

Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University. I'm so excited to have here with me today, Dr. Ravi Parikh, who is an Assistant Professor of Medicine at the University of Pennsylvania, and Dr. Lova Sun, who is a third-year Fellow at the University of Pennsylvania. Thank you so much for being here, both of you.

Lova Sun: Thanks for having us.

Ravi Parikh: Thank you.

Alicia Morgans: Wonderful. I wanted to talk with both of you about a recently presented paper, really thinking about cardiovascular disease in veterans with prostate cancer. Lova, can you tell us a little bit about why you wanted to investigate this population? And what is the importance of cardiovascular disease in this population?

Lova Sun: Yeah, absolutely. We know that cardiovascular disease is a big problem, a leading cause of mortality and morbidity in patients with prostate cancer, especially in light of improving treatment and survival outcomes in this population. And we also know that androgen deprivation therapy has been linked to cardiovascular risk factors and may worsen cardiovascular risk in these patients.

Professional society guidelines do recommend regular screening and assessment of cardiovascular risk factors in patients with prostate cancer, starting androgen deprivation therapy, but we really didn't know how well adherence was to these guidelines and what proportions of patients were actually being appropriately screened and assessed. So, we wanted to look at this question in the US veterans population, which, as you know, has a high prevalence of both cardiovascular diseases, as well as prostate cancer, and kind of get a quantification of how well these guidelines are being followed nationwide.

Alicia Morgans: Great. Ravi, can you tell me, how did you construct this data set to really look at and investigate that question?

Ravi Parikh: Sure. We took a cross-sectional analysis of US veterans who were diagnosed with both localized and advanced prostate cancer between 2010 and 2017. We chose that time period because, actually, in 2010, in recognition of some of the potential cardiovascular effects of ADT, the USFDA issued a black box warning around the cardiovascular risk of gonadotropin-releasing hormone agonists, as well as a joint scientific statement from the AHA, ACS, and AUA coming out, which recommended assessment for cardiovascular risk factors.

So, as part of the creation of this cohort, we took a cohort of veterans who were seeing primary care within the VA to try to make sure that we were capturing respect or assessment among a cohort that was primarily receiving care within the VA. We applied some additional exclusions around individuals who had inadequate data capture and inadequate demographic information, in particular, inadequate data around whether or not they received hormone therapy or not. We defined an 18-month study period, defined as the 12 months before to 6 months following the date of ADT initiation to actually identify our measurement period for assessing both cardiovascular risks, uncontrolled cardiovascular risk factors, and management of those cardiovascular risk factors.

Alicia Morgans: Great. Lova, what did you find when you looked into this?

Lova Sun: Our major finding, first of all, just looking at the study population as a whole, we found that the rates of comprehensive cardiovascular risk factor assessment, which we defined as measurements for cholesterol, glucose, as well as blood pressure did improve over time from 2010 to 2017. But even in recent years, over 1 in 5 veterans did not receive comprehensive cardiovascular risk factor assessment. We were also interested in the question of how the initiation of ADT impacted these rates of assessment, as well as risk factor control and therapy. And while we found that patients with known cardiovascular disease did have better rates of assessment, as well as management, the initiation of androgen deprivation therapy actually did not seem to impact these rates and be making providers more likely to comprehensively assess and treat these cardiovascular risk factors.

Alicia Morgans: Well, that's really concerning and certainly not consistent really with the guidance that was given by the American Heart Association, and absolutely something that could affect our patients. A lot of times in the VA system, there is multidisciplinary care around these patients. Were you able to look at that and to make sure that they didn't have these assessments done through different providers? That seems to be, really, a strength in the VA dataset.

Lova Sun: Yeah, I absolutely agree, and that is one of the reasons we decided to use this VA data set, was because this is a population that generally receives coordinated, comprehensive care that we can assess relatively validly using this data. And as Ravi mentioned, we did exclude patients without a PCP visit within the VA system in order to try to make an even more clean population with coordinated care within the VA. And so, even with those strengths, we did find that assessment of these risk factors, using all the data that we have available, did show the deficiencies that I mentioned, with over 1 in 5 veterans not receiving comprehensive assessment in recent years.

Alicia Morgans: Wow. Well, Ravi, given that we are able to shine a light on this issue, and I have to say, it's not exactly a surprise, but so important to shine a light so that we can actually reflect back to ourselves what is actually happening in practice. What are we going to do about this? Not just in a veteran's population, but I imagine it is a similar situation in other populations, potentially, as well.

Ravi Parikh: Absolutely. Just to build off of Lova's point, I think it is useful to consider that we really try to enrich a population for individuals who had the highest chance possible for cardiovascular screening, individuals who had primary care assessment, of course, individuals within the VA. So you can imagine, in the general population, we would hypothesize that this is potentially even more of a problem. I think for me, it sort of forces me to think back as to how I approach cardiovascular risk assessment as an oncologist.

One, what our study suggests is that a preexisting diagnosis of ASCVD is really what determines whether you get accurate risk assessments, and I think that is because ASCVD assessment is usually done in the primary care setting, what it suggests to me as a potential hypothesis-generating finding is that we as oncologists are potentially leaving cardiovascular risk assessment to others, including primary care, when really, for individuals who are starting on ADT, that burden of cardiovascular risk assessment probably should be falling on us, given how closely we are following these patients in the treatment setting. And so I think that that is one insight that has made me sort of more cautious and into how I am doing this at baseline.

I think the other thing that it really sort of forces me to think about is how I manage my time when I'm initially seeing a patient because we know that ADT risks of cardiovascular disease are often highest in the initial 6 to 12 months after initiation of ADT, and so you think about the period when you are seeing your initial consult for a patient with localized or advanced disease and how much is just going on. How much you want to talk about the treatment that they are going to initiate, how much you want to talk about side effects, how much you want to talk about the variety of other survivorship-related concerns that an individual might face.

But I think what it tells me is that we really need to have carved out time where we are talking to patients about this, and potentially even behavioral reminders to do this so that it is not entirely on the cognitive burden of the clinician to remind ourselves to do this, but potentially could be in the hands of automated reminders in the electronic health records or utilizing some of our other colleagues as part of our multidisciplinary oncology team to really make sure this happens within the first 6 months of starting ADT, otherwise I think we are missing an opportunity.

Alicia Morgans: I agree. I also agree 100% with the need for systems-based reminders, triggers, and really coordinated efforts to take care of these patients because we are relying on the memory of a clinician while he or she is trying to keep up with all the other things in the clinic that day, can be really difficult, and frankly isn't necessary anymore. As you mentioned, we have a lot of other systems and ways to really support us. So definitely something for us to think about in the future, as well as maybe really definitively defining guidelines around how we can care for these patients, because that is something else that I see is not necessarily clear. What exactly should we be doing in terms of cholesterol management? What exactly should we be aiming for in terms of blood pressure management? Should it be the same as patients who have histories of cardiac disease, are there other goals? Are there other things we should be looking for? So really bringing so much to light with this work. I congratulate the two of you.

As we wrap up, I'd love to hear a closing thought from you, Lova, and then from you, Ravi. What would your message be to clinicians as they are trying to understand your findings and really implement something in their clinic to hopefully make a change? What do you think, Lova?

Lova Sun: Yeah, so I think my major takeaway from this paper is we know that cardiovascular disease is a big issue in this population and this paper really highlights the ongoing need to be not only assessing, but also finding better ways to target and manage these risk factors in this population, in particular patients who are starting androgen deprivation therapy who we know are at even higher risk of some of these cardiovascular events. And as Ravi pointed out, it also highlights an opportunity, I think, for us to incorporate other providers, be they primary care, cardiology, cardio-oncology, and really have a more integrated method to optimize this very important part of prostate cancer patients' treatment, as well as survivorship courses.

Alicia Morgans: Great. Thank you. And, Ravi?

Ravi Parikh: Yeah. Lova and I are very intervention-minded individuals, so when we were generating some of these results, our mind immediately jumped to, "Well, what can we do in terms of even small-scale changes within our local VA to try to prompt better cardiovascular risk assessment and management?" And I think a couple of things really became salient to me.

One is that just to reinforce the point before, this can't rely solely on the cognitive burden of the treating urologist, radiation oncologist, oncologist. That is a recipe for failure. We know that even an FDA black box warning, if that's not to be something that changes behavior, then I think we really need to get down into the local system and find out how we can use strategies like defaults, automated reminders, performance reports, to really try to get down into the local level and then try to engender behavior change the way that we have done for, honestly, cardiovascular screening at the primary care level. I think that we can learn a lot from how widespread that has become and how much that has grown in our local population of individuals initiating ADT.

I think the second thing is that patients with prostate cancer are living longer, and ultimately, for a lot of our men with localized disease, and occasionally for men with metastatic disease, they are reaching a point where prostate cancer isn't their biggest active issue. And I think as that point occurs and as individuals in the metastatic setting, in particular, are living longer, we need to still be attentive to this because cardiovascular-related death is one of the leading causes of mortality and morbidity in prostate cancer patients. And so, even in this study, we found a significantly lower rate of assessment among individuals with advanced disease, which really suggests that we need to build this into bundles of care at the initiation of treatment so that we are doing the best for our patients.

Alicia Morgans: Absolutely, because at the end of the day, also, ADT is an incredibly effective tool against prostate cancer. It does its job, it just has these effects. We need to do what we can to mitigate those effects, keep our patients safe, while we are also controlling their cancer. So I sincerely appreciate the two of you doing this work and for taking the time to really unpack it with me and talk about the clinical implications so that everybody can really benefit. So, thank you so much for your time and your expertise.

Lova Sun: Thank you so much for the opportunity.

Ravi Parikh: Thanks a lot.