The Evolving Heart Health Landscape

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Welcome to MedEvidence!, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts Hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Michael Koren: 0:11

Hello, I'm Dr. Michael Koren, the executive editor of MedEvidence!, and we have a really special podcast today. I get the opportunity to meet lots of different people and talk to different people through these podcasts, but I have to admit it's always the most fun for me when I have a kindred spirit or a kindred soul to talk to. And today I'm going to be speaking with Seth Baum, who I think qualifies for that, and Seth and I have known each other for a long time. He's a fellow preventative cardiologist, although has a history of also doing interventional cardiology, and he and I have been very involved in a lot of research together over the years, including multiple publications together, and I want to invite you a warm welcome to MedEvidence!, Seth, and we're going to have some fun talking about trends in cardiovascular disease and really some of the important elements of clinical research about how to keep patients engaged in these trials.

Seth Baum: 1:04

Well, it's great to be here.

Seth Baum: 1:07

I hope you don't hold my interventional cardiology background against me. Yeah, it was a good period of my life, but preventive cardiology is certainly a better one. So it's great to be here to talk to you.

Michael Koren: 1:19

So a lot of people are listening to this, don't understand all the nuances, but, like every other field, cardiologists come in different flavors and we all love each other, but we have these internal debates, these little sibling rivalries within our profession. So interventional cardiologists are a little bit different than preventive cardiologists, who are a little bit different than heart failure cardiologists, who are a little bit different from epidemiological cardiologists or EP electrophysiologists. So we all have our little niche and we like to tease each other on occasion about the pluses and minuses of our niches. So thank you for that, Seth. So, Seth, tell the audience a little bit about your background and how you got to where you are today. Which isa leading expert in cardiology. In fact, the President of an important society, the past President of an important society that deals with these issues.

Seth Baum: 2:09

Yeah, so, as you noted, I started in interventional cardiology and actually electrophysiology as well, so I had both of those fields. And around 2000, I totally shifted my focus to lipids and cardiovascular disease prevention and I grew in the fields. I learned a great deal. I've had a good time helping educate as well. I was the president of the American Society for Preventive Cardiology. I'm currently the chairman of the board for the Family Heart Foundation, which is a nonprofit that focuses on familial hypercholesterolemia and Lp(a). And then, as you know, I started a clinical research site just under 10 years ago in Boca Raton. Then that became Flourish Research. I'm the chief medical officer of Flourish Research and you, of course, are the chief scientific officer. So now we get to work together after having known each other for quite some time.

Michael Koren: 3:14

Yeah, it's been fun. So we're both working in this network of sites now that are represented throughout the country. I'm in Northeast Florida and Seth is down in South Florida, so it's been a fun journey and the journey continues. So thank you for that, Seth.

Michael Koren: 3:31

So let's talk about the macro issues in cardiovascular disease, and we're both driven by the fact that during the course of our career in cardiology, we've seen a dramatic drop in cardiovascular death rates. So, those of you who are non-cardiologists or are not familiar with the data, the death rate for cardiovascular disease peaked in the United States in the late 70s and between 1980 and around 2012 to 2015, there was a dramatic drop in cardiovascular disease death rates in our country, and this death rate sort of bottomed out around 2012, 2015. And unfortunately, over the last 10 years, it's ticking back up. So during this drop of 30 plus years, we saw a 60% reduction in cardiovascular disease mortality in the United States. Truly remarkable. It's one of the most incredible stories about the success of the healthcare system, but equally remarkable in the opposite direction is the fact that we haven't made progress in the last 10 years. So let's start the conversation, Seth, by giving the audience insights into why we've stalled. Why did we stop making progress?

Seth Baum: 4:51

Well, I don't think anybody knows for certain that there's a one specific thing that has caused this shift, but we can look at risk factors that predispose to cardiovascular disease, to cardiovascular events and death, and we can see what has happened with those risk factors. For example, one thing that can be attributed to the great improvement would be smoking cessation that occurred. There was a strong smoking cessation push during those earlier years. It was very effective. Dietary changes were implemented that were effective

Michael Koren: 5:35

And changes in the food industry.

Michael Koren: 5:36

The food industry was selling different food.

Seth Baum: 5:39

Totally different food and, frankly, the American Heart Association and other organizations were supporting different foods at that time as well. So there were a number of influences. People were lighter, less heavy, they were exercising and the country was in this preventive position, if you will. Something shifted, right? The American Heart Association made a shift in its dietary recommendations that, some might say, have helped lead to an increase in weight among Americans. This focus on carbohydrates at the expense of fats maybe became a little too extreme and people started gaining weight and, of course, with weight gain came diabetes, came inflammation, came increased fibrosis in various areas such as the heart. And there are a number of factors that occurred there.

Seth Baum: 6:42

I'll stop there. I'll give you the opportunity.

Michael Koren: 6:43

I was going to say hats off to our interventional colleagues who have helped reduce the mortality rate of acute MIs. So when we started our training in the late 80s, the heart attack death rate was north of 20% and now it's considered less than 5%. So there's been huge advances in terms of acute care. Icus are much better than they used to be, so when you get sick we're much more likely to bail people out than we were 30 years ago.

Seth Baum: 7:12

That's very true and I, as a former interventional cardiologist, of course should have highlighted that. So thank you, but that is very true. And of course we have new medications that reduce cardiovascular event rates. Lipid-lowering therapies have, of course, improved. We have many studies to demonstrate their effectiveness. So there are a lot of medical and interventional approaches that have helped that helped that very dramatic decline in cardiovascular event rates. They're now being offset by those shifts, I believe, in diet, in weight, in diabetes, in NASH or MASH, I should say, and heart failure and so many other things.

Michael Koren: 8:02

I think we should also point out specifically that statins probably had a huge impact in improving cardiovascular morbidity and mortality and during this period between, let's say, the late 80s and the early 20-teens, there were statins on the market that were being promoted by the pharmaceutical industry, so we were constantly being reminded by salespeople, basically, from the pharmaceutical industry, to get the cholesterol down, use these drugs and they worked, and we did a lot of cardiovascular trials. These are huge outcomes trials now that show that people who were involved in these trials, comparing statins with placebo or high doses of statins versus lower doses of statins, did better and it was unequivocal and unfortunately, I think that message is getting lost a little bit. I don't know if you agree with that.

Seth Baum: 8:52

Yeah, I would just say that's a really interesting point about the pharmaceutical reps. You know, I remember a statistic that five years out from our training, the greatest education used to come from the pharmaceutical reps, and of course that was then frowned upon, and there are physicians who don't allow them in their office today. Yet we were learning a lot and it was top of mind. So that brings up the fact that today, after an acute infarct a year down the road, less than 50% of people are actually at goal and maybe 70 or 80% are not at goal.

Michael Koren: 9:30

We're talking about cholesterol and lipid goals?

Seth Baum: 9:31

Correct.

Seth Baum: 9:32

And in some studies, 50% are not even taking their statin or any lipid lowering therapy. Right, you know, that's another part of why we're falling short. We're not treating the patients adequately who we could be treating.

Michael Koren: 9:46

Yeah, yeah. Were you involved in the Victorian Initiate study? Remind me of that.

Seth Baum: 9:51

Not the Initiate.

Michael Koren: 9:52

Yeah, so I was the lead PI for that, principal investigator for that, and that was remarkable. That was a different study. Instead of using a placebo-controlled, we had a quote situational control of usual care versus aggressively using advanced therapy when patients were not at their LDL goals, and we found that only 7% of people in usual care got through their LDL goal, despite the fact they were in a clinical trial and despite the fact they were being reminded over and over again during the course of a year. So that just shows you that there's a lot of inertia and I think that's fundamentally changed, because there's not much discussion about that in the doctor's office the way they used to be 20 years ago.

Seth Baum: 10:39

I think you're correct. The Family Heart Foundation has some data showing, you know, around 20% or so of individuals you know a year out from acute coronary syndrome are at their goal. So and it is. You know, there are multiple stakeholders involved in this issue. We have the payers, who push back on some of the therapeutics we can use. We have physicians who have clinical inertia. We have our guidelines that, in 2013, gave us basically the wrong message, sent the wrong message, and we're trying to recover from that. We have patients who are seeing things on the internet that are making them feel that these medications are not for them for a variety of reasons. So it's multiple problems that we have to confront.

Michael Koren: 11:28

Right. So I guess the good news is that we're working hard to offset that. So both you and I are very involved in clinical research, trying to make it simpler to get your cholesterol levels down, trying to treat targets that we couldn't treat before, such as lipoprotein( a), and also making compliance easier for people by using longer acting products. So maybe you can tell the audience a little bit about some of that work.

Seth Baum: 11:56

Yeah, no, I think frankly, you just did so. There are multiple trials. If you talk about Lp(a), there are multiple drugs in development. Lp(a) for the audience, if you don't know what it is, it's like a really bad kind of LDL. It's a smaller particle. It increases inflammation, increases thrombosis and increases atherosclerosis. So it's a triple threat, we say. Highly prevalent 20% of the population, Blacks, 30% of the population, South Asians 25% or so of the populations and, frankly, Hispanics may be a little lower than the 20%, but very highly prevalent and very tightly correlated with event rates. So we've done a number of clinical trials. There's a few phase three studies ongoing right now and hopefully we'll get to the point where we have a therapeutic in the not too distant future to address and solve the problem.

Michael Koren: 12:58

Yeah, so these are very, very important studies that are going on and, as you alluded to, these are studies that run over an extended period of time, and so one of the challenges for a clinical investigator is to keep their patients engaged and involved in the study, especially when they're placebo controlled studies, where certain members of the population won't be on an active therapy, and, quite frankly, nowadays you can kind of cheat and figure out what you're on, and that is a phenomenon that we have to deal with. So why don't you explain that a little bit to the audience and why this is such an important issue for clinical investigators?

Seth Baum: 13:36

Yeah, well, first, the overarching cardiovascular outcome trial. It's important to understand that type of study. That's a study where we typically use a placebo and compare it to an investigational product, a drug that's in development. These are very long studies. We're looking at events, typically heart attack, ischemic stroke, cardiovascular death, sometimes hospitalizations or interventions. So we look at these event rates and it takes a long time for them to accumulate and, frankly, we don't want the studies to be truncated or too short because in that case we might not see all of the potential benefits that can occur.

Seth Baum: 14:14

So these are you know, from a statistical standpoint have to be very carefully planned and executed. So that's basically what the cardiovascular outcomes trial is. We need people to stay in, we need people to take their medicine, we need people to be blinded, not to know what they're taking and then to complete the trial to get the best results. The problem, as you mentioned, in some of these lipid and lipoprotein studies, like Lp(a) or LDL studies, is that patients sometimes can go to their physician's office and get their lipids drawn or lipoproteins assessed and they can figure out whether or not they're on drug, if they respond to that by either dropping out of the study or taking an additional medication that they're not supposed to take. It clouds our data. It makes it harder for us to understand what's going on.

Michael Koren: 15:06

Really it compromises the whole experiment.

Seth Baum: 15:08

Right.

Michael Koren: 15:08

Yeah. So, Seth, let's take a quick break right now and then on the other side, what I'd like to talk about is specific strategies to keep people in studies, starting from the very beginning of their enrollment. As experienced clinical trialists, I think we might be able to have some insights that we can share with other people.

Seth Baum: 15:27

Sounds great

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Welcome to MedEvidence!, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren: 0:11

Hello, I'm Dr Michael Koren, the executive editor for MedEvidence!, and Dr. Seth Baum and I were having this fascinating discussion about cardiovascular disease death rates and how we're using clinical trials to work on reinstituting a trend towards lower mortality which kind of stalled over the last 10 years.

Dr. Michael Koren: 0:34

So we'd invite you to go back to the previous talk, if you haven't heard that, to get a little bit more information about what's happening epidemiologically. But now I want to talk to Seth, who is a fellow cardiologist and a fellow clinical trialist, about what we need to do to keep our patients engaged when they get involved in clinical research. And this is so important because the success we've had to date has involved people staying in statin trials and other cardiovascular risk reduction trials over an extended period of time, and in order for us to have continued success, we have to encourage people now to get into trials with new therapies and to stick with those trials. So, Seth, start us off by letting us know, when you recruit a patient from the very beginning, how you think about retention issues and keeping them in trials.

Dr. Seth Baum: 1:23

I think that's a great question and a great point, because retention in a cardiovascular outcomes trial is paramount, right? If you have a high dropout rate, your data are going to be terrible and you won't be able to prove your point, if it's provable.

Dr. Michael Koren: 1:43

And, by the way, good products have gone by the wayside because of flaws in the trial and flaws with retention. So, at the end of the day, if people don't complete the trials, you won't know if the product actually works.

Dr. Seth Baum: 1:58

Right. So the discussion with the participant, in my view, has to happen day one at the time of signing of consent. The discussion really should center around the fact that it's a cardiovascular outcomes trial that has to be explained. The value of a cardiovascular outcomes trial has to be explained. For example, we know from a good deal of data that participants in cardiovascular outcomes trials who are on placebo have lower event rates, much lower event rates, than their counterparts in the real world.

Dr. Michael Koren: 2:35

Isn't that crazy, it's crazy, it's crazy, and sometimes we call that the Hawthorne effect. Yeah, do you believe in that?

Dr. Seth Baum: 2:44

So I'm not sure what the frankly, what the cause is in. You know, I have some ideas what the cause is in terms of, specifically, a cardiovascular outcomes trial, but I think it's clear that it's that, being in a trial, in a long-term cardiovascular outcomes trial, participants do a number of things such as adhere to therapeutics right.

Dr. Michael Koren: 3:14

More interaction with the healthcare system

Dr. Seth Baum: 3:16

Interaction with healthcare system, more eyes on them. They take it more seriously. There are so many factors that come into play that can lead to this benefit and, interestingly, Eugene Braunwald has been quoted as saying that, were he to have a cardiovascular event, a heart attack, let's say, he'd like to be enrolled in cardiovascular outcomes trial and placed on placebo. So yeah, so you know I, there's truth to this.

Dr. Michael Koren: 3:46

Yeah, Eugene Braunwald is arguably one of the most famous cardiologists in the country he's he's in his nineties now.

Dr. Seth Baum: 3:53

He is he's like 93, I think 93, 94. He was your, a mentor of yours, right?

Dr. Michael Koren: 3:59

He was. Yeah, he was an attending physician when I did my third year medicine clerkship at Beth Israel Hospital in Boston, so I had the great privilege to be one of his mentees.

Dr. Seth Baum: 4:11

Yep, yep. So we have that discussion. We really actually go through this, everything we're talking about now. We really discuss with the participants. We get them to agree that their intent is to stick with the trial. Now, you know you can't strong arm people, you know, and force them to do this, but certainly from the outset of a study they need to buy in, otherwise, frankly, they should not be included in the study.

Dr. Michael Koren: 4:42

Yeah, and that's a really, really important point is you can identify people who may be getting into the study for the wrong reasons and it's very important that you call that out if you identify that behavior. So if somebody gives you the inclination that they're going to try to cheat and find out what they're on and use that information to determine whether they stay in the study, please don't include those folks because it hurts the participation of everybody else.

Dr. Seth Baum: 5:12

Yep, it's true. And then, moving on from that initial visit, I would say probably the most important factor that will help retention is having a good interaction between the study participant and the staff. That includes the coordinators, the investigators, the front desk. Frankly, you know, shorter wait times for an appointment. Everything's got to move smoothly and the participants have to be happy and they have to look forward to coming to the site when things go wrong. A quick call, a conversation, you know, that kind of thing can go a long way as well.

Dr. Michael Koren: 5:58

Yeah, clinical trial as a service. Unfortunately, in the current medical environment a lot of clinical care is very rushed. People don't feel the service element of routine clinical interactions, that we can give them that experience in the clinical research realm. So I think it's important to emphasize that, as you point out. So that's a really, really good point. How about other little things, little perks, little educational tidbits? Do you find that that works?

Dr. Seth Baum: 6:29

Educational tidbits, in terms of educating the participants? Is that what you're talking about.

Dr. Michael Koren: 6:32

Yeah, making sure that there's something that is provided to each participant, that's individual to them, at each visit, that makes them feel that they're getting a special education being part of a clinical trial.

Dr. Seth Baum: 6:44

Well, I'm not sure whether you have a particular thing in mind and I'd love to hear if you do. But certainly what we do and I would emphasize, others do is, at each visit, to have the discussion to reinforce why the participant is in the study, reinforce - for lack of a better term - good behavior, adherence, reinforce the value to the participant and, frankly, the value to the world it's both and even to reinforce the fact that we know that if the participant is on a placebo, the participant is still getting benefit from being in the study. So those things are what we do and I'd love to hear what else you have.

Dr. Michael Koren: 7:33

Yeah, you touched on a number of things that are really important tactics. I'll give you an example of specific value. So I practice what I preach and I eat fish most days of the week. I don't know if you're a fish eater or not. I don't like fish.

Dr. Michael Koren: 7:46

Okay, well, I'm a big fish guy and so I will share with patients my recipe for halibut, which is my favorite fish to prepare at home, and not that I'm a huge cook or anything, but I love to actually cook fish at home and I have this recipe for a mustard halibut that I'll share with a patient, and people love that.

Dr. Michael Koren: 8:09

Or I'll tell them how you can use how to get more omega-3 fatty acids in their diet through different things. And then your point about this concept that we share our data and our experiences with other investigators from around the world. People are fascinated by that, so I'll tell them a story about how people like you and I will go to the American Heart Association meeting and give a presentation or write a paper and how important it is, and that, at the end of the day, their participation gets amplified to physicians and other healthcare providers around the world. So the experiences here in Florida actually will change behaviors in India or influence people in Germany, et cetera, et cetera. So to me that's an exciting part of that and I think patients get a kick out of that to know that, and they otherwise wouldn't have that knowledge unless we engage them at that level.

Dr. Seth Baum: 8:59

Yeah, I think that's great. Those are great tactics you utilize. It's very nice of you to share your halibut recipe and I think my wife would like that.

Dr. Michael Koren: 9:07

It's a secret, only if you sign up for a clinical trial will I reveal that secret.

Dr. Seth Baum: 9:14

You got to let me know for my wife. I won't eat it but she would love it.

Dr. Michael Koren: 9:18

Yeah, the IRBs have looked at that as as coercion, but I got it passed.

Dr. Seth Baum: 9:29

That's funny, it's that good?

Dr. Michael Koren: 9:30

It's that good, yeah, anyway. But people love that and again, they actually need little tidbits and tips to help them complying with exercise. A lot of people have the right intentions but they don't know how to master the logistics, and I think part of the conversations we can have help them master those logistics.

Dr. Seth Baum: 9:47

Yeah, and the reinforcement they get when they come to the site is invaluable. When you reinforce those behaviors and you acknowledge when they're doing things that are benefiting themselves, I think that's very valuable. The connection to the rest of the world is really valuable as well, and we have those discussions too. And genuinely participants typically genuinely appreciate helping the world and it's true, right, you and I, as clinicians, help a lot of patients but, as in our clinical research, we help millions and hundreds of millions of people.

Dr. Seth Baum: 10:29

Right, billions of people. In some studies, so like in LP( a), it's going to be billions of people.

Dr. Michael Koren: 10:37

So, yeah, no doubt, yeah.

Dr. Michael Koren: 10:40

And the flip side of that, by the way, is if a patient drops out of a study, particularly if we kind of lose contact with them, then what happens is that that data point gets lost and there's a possibility that that will compromise the study to the point where we don't learn the truth.

Dr. Michael Koren: 10:58

And not only does that have an effect on the individual who's the one that dropped out, who won't get the feedback and the information that comes at the end of the study, but that'll affect the participation of everybody else that's participating in the study potentially. So I think most people, even if they're fed up or they're tired or they're fatigued, they don't want to compromise the experience of other people and making them aware of how that works. So just to fill in a detail there if you get lost to follow up in a study, we often have to assume that you've died, whether or not you have died. So for statistical reasons, you look at it as somebody that has had an event that will perhaps create some impact on the entire study, because that's an inaccuracy and with that inaccuracy you won't know the real truth. So these are very, very important concepts to let people know about. The other concept that's important is that let patients know that they can stop taking the study medication but still be in the study.

Dr. Seth Baum: 12:12

Yeah, yeah that's a great point. Some investigators are confused about that, and believe that if they stop the investigational product, then that's tantamount to withdrawal of consent and it certainly is not. So we like to follow our patients throughout the, you know, till the end of the trial. Even so, optimally, we want them on an investigational product. If they can't be on an investigational product, we want them coming in for all their visits. If they refuse to go in for all their visits, we say how about on the phone? If they refuse on the phone, we say, okay, let's check in with you, you know, once a year. If they refuse that, okay, we'll check in with you at the end of the study.

Dr. Michael Koren: 12:42

Exactly, that's right.

Dr. Seth Baum: 12:43

Right, so we have this hierarchy of our preferences, but we never, ever, want to go down the withdrawal of consent rule if we can avoid it.

Dr. Michael Koren: 12:55

Right, and even if we just know their vital status, that is better than the alternative. And the other thing to point out is that often we find out things during the course of the study that benefits patients who are on the active product, and often the sponsors will make that product available to patients if they stick with it. So there's been a number of examples where investigators like Dr. Baum and myself are lobbying the companies to allow people to have open label access to these products at the end of the study. They don't always do it, but often they will, and that really depends on people sticking with the program so that they may get access to those products.

Dr. Seth Baum: 13:36

Right, it's an important point.

Dr. Michael Koren: 13:39

And then you know it's always just good to be charming and to let people know that they're valued. People need to hear that and that you'll do whatever you can to help them in ways you may not anticipate. So sometimes people come in and they personally don't feel like they're getting anything out of the study, but they mention a family member and for the staff and physician to be open to figuring out what you can do. So, for example, you mentioned lipoprotein( a) or Lp( a) is what we like to call the really really, really really bad cholesterol and, for example, you have resources for people, including family members, to get this tested for free.

Dr. Seth Baum: 14:23

That's true Through the Family Heart Foundation. You're absolutely right, and they could certainly go online and look into that. There's also the cascade screening elevated Lp( a) to have the entire family, first starting with the first degree relatives, then moving out tested for Lp( a) to identify at-risk individuals, and that's very important. We do that for familial hypercholesterolemia as well. So these genetic disorders, they're family diseases, they're not individual diseases. Very important and a real benefit to the participant. You know there's another benefit as well you bring up, you know, valuing them and just being nice. We do see lab aberrations during the course of a study and often the investigators will call the participants' physicians and have a discussion and bring something to their attention that they otherwise would not have been aware of and that can really impact the participants' health.

Dr. Michael Koren: 15:29

Oh, great point. And multiple times we've picked up other things during a study that have made huge differences in people's lives. So really good point. Again, as clinical investigators, we have an attention to detail that's absolutely required. That really results in things that do affect the people who are in the studies, whether or not you're on the active drug. So I think that's a really good point. Seth, this has been an amazing conversation. Hopefully we'll share it with a lot of people. Hopefully this will help other physicians and patients understand the importance of sticking with it once you get involved in a study, particularly a long-term outcome study, which can lead to fatigue during a period of time but it's really important that people understand why sticking with it makes a difference both for themselves, for their family and for society at large. So thank you for the conversation and we'll definitely get you back to MedEvidence! and talk about some other things in great detail. Thank you, Seth.

Dr. Seth Baum: 16:32

It's been a lot of fun, Michael.

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