Announcer:
0:00
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
Announcer:
15:28
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