Dr. Michael Koren and Dr. Dennis Leahy wrap up the MedEvidence Lipoprotein A series by exploring Lp(a) clinical trial treatments. Dr. Leahy shares his personal clinical research experience and platform for encouraging everyone to have their LP(a) blood work drawn. Tune in to learn more about this lesser-known condition, possible treatment options, and the future of Lp(a).
Dr. Dennis Leahy is a retired interventional cardiologist living in San Diego. He received his education from Princeton University and Columbia University and his residency at the University of California. In addition to enjoying the opportunity to surf and golf, he has maintained a personal and professional interest in Lipoprotein A research and treatment.
Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.
He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.
Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been pub
Dr. Michael Koren and Dr. Dennis Leahy wrap up the MedEvidence Lipoprotein A series by exploring Lp(a) clinical trial treatments. Dr. Leahy shares his personal clinical research experience and platform for encouraging everyone to have their LP(a) blood work drawn. Tune in to learn more about this lesser-known condition, possible treatment options, and the future of Lp(a).
Dr. Dennis Leahy is a retired interventional cardiologist living in San Diego. He received his education from Princeton University and Columbia University and his residency at the University of California. In addition to enjoying the opportunity to surf and golf, he has maintained a personal and professional interest in Lipoprotein A research and treatment.
Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.
He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.
Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been pub
Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts, powered by Encore Research Group and hosted by cardiologist and top medical researcher, Dr Michael Koren.
Speaker 2:
Hi, I'm Dr Michael Koren leading another episode of MedEvidence with a fabulous guest, dr Dennis Leahy, and Dennis has been sharing some really personal details with us about his journey with atherosclerosis that has been driven by this really, really, really, really bad cholesterol molecule called lipoprotein little a, and Dr Leahy has been exposed to apheresis, which is a filtering or dialysis type technology to get rid of this bad protein, and he's also been part of a clinical trial that uses an antisense oligonucleotide or ASO, which is a sort of a genetically mediated way of getting LPA levels down very, very low. And he has good reason to do so. He's been through a lot he's had bypass surgery, he's had multiple stents placed, he's had complications after a stent placement and even had a carotid endarterectomy to deal with a carotid lesion that was probably causing a little mini stroke. So Dennis, as an interventional cardiologist, has put a lot of effort in not only living this but also studying it, and so we're going to jump into that discussion about research and where the future lies in terms of treating this lipoprotein disease.
Speaker 2:
And, from our viewpoint here at Jacksonville Center for Clinical Research, we've been very involved with a number of studies. So we actually have used the drug, pelacarcin, which Dr Leahy has been part of as a clinical trial participant, and we're also working on some products that use a technology called small interfering RNA to get lipoprotein little a levels down to extremely low numbers, in fact up to 95% reduction in LPA. So we'll jump into that a little bit more. But so first, before we go into that, dennis, you know I'm very passionate about clinical research and I think everybody should be in a clinical trial and tell us what it was like. Do you feel like a guinea pig? Or tell us how it was for you. It must be tough for a doctor who's usually on the other side of therapy to be part of a research study.
Speaker 1:
What was that like for you? Well, you know, when I entered that study, as we touched on earlier, there really wasn't anything else presently available that was going to be helpful. I did go down the niacin route for a while, but it just, you know, the kind of doses you have to take to achieve what you want to achieve is they just weren't tolerable. You couldn't tolerate it, yeah it. So I had no trouble. As I mentioned the clinical trial I entered into, as opposed to the, you know, a double-blinded randomized trial, which is frequently you either have placebo or you're on treatment, this was a dosing trial, so I had an 85% chance of being on an active drug, which really appealed to me. I was very comfortable with it. We did a number of trials, a number of drug trials in my practice, and so I was very familiar with the protocols and and kind of the pluses and minuses, so I had no reservations about it and it you know it really worked out extremely well.
Speaker 2:
Yeah, one of the things I like to remind the audience is that for people who have never been exposed to clinical research, it sounds very intimidating and scary, but once you've done it, people actually love it.
Speaker 2:
It's a very nurturing experience and you learn a lot about your disease.
Speaker 2:
You get access to things, in many cases, that you didn't get previously, and in many cases you get a stipend for your time and effort.
Speaker 2:
So there's a lot of reasons to like participating in clinical research, and my favorite statistic to quote are surveys that have looked at willingness to participate in clinical trials, and when you take naive members of the lay population and ask them whether or not they would be willing to do a clinical research study, depending on the survey, between 40 and 60% of people said they'd be willing to do it. But once somebody has done one trial and you ask them if they would do a second trial, that percentage goes up to 97%, and here in our offices in Florida that number is 99%. So 99% of our patients exposed to one clinical trial willing to do a second, and I think that states a lot about how neat of an experience it is for virtually every patient. And it's interesting to hear your perspective, dennis, as both a clinician, a research-oriented person and somebody that actually participated in the trial. So again, thank you for your participation and thank you for spreading the word.
Speaker 1:
Well, I think you know really the thing that I, you know I'm retired, so I'm kind of in the game in a very limited capacity. But the thing that I have actually written a couple of pieces on that have been kind of op-eds that have gotten on a couple of online sites is, I feel, very passionate that everyone in the world should be tested for their LP little a level. I think it's an extremely important part of where we're going with LP little a. I don't want to get too far in the weeds if this is not something you want to pursue, but you only need to be tested once to be essentially to stratify your risk, because the level doesn't change much from age five onwards. Your LP little a level is going to be your LP little a level.
Speaker 2:
That's a great point. It's a really really super great point and thank you for making that. So you know, with cholesterol and some other lipid parameters your diet has a big impact, your physical activity has a big impact. But for LP little a, it's mostly genetically mediated, virtually all genetically mediated. The thyroid may have a little bit something to do with it, maybe a little other things, but to your point, you either have a lot of it or you don't.
Speaker 1:
Well, lp-lil-a has kind of suffered a weird history in that it really hasn't ever gotten the attention it deserves, even though I think, particularly the past decade, the elegant research that you and other people have been involved in, have really clarified its role and given a direction to how we should treat it. But that has not translated well in the clinical world. You talk to the average doctor on the street and ask them about Lp little a and they're still kind of mystified, and part of the reason for that is it was always thought to be non-modifiable, but now we know it is modifiable and probably safely so. Modifiable, but now we know it is modifiable and probably safely so. Um, but even before these medicines get approved, there are things that people with elevated lp little a who are 20 years old should be doing. Uh, you know, primarily being very attentive to their risk factors, but particularly their ldlc levels.
Speaker 1:
Um, correct, you know, if you're in the top quartile, like I am, you know this, you're already. You're already having some troubles, probably, I don't know if you recall in medical school I was in medical school a good 15 years before you, but it was always preached that this is a lifetime disease and one of the things that were always cited was people. Soldiers that came back from the Korean war had autopsies and they, a lot of them, had fatty streaking in their arteries. They probably all had LP little a, because it does affect 20% of the population to the level that they're going to have significant elevated risk.
Speaker 2:
That's a great point, great point, eye-opening that even people who seem completely healthy in their 20s were already developing signs of atherosclerosis.
Speaker 1:
And I'm pretty sure had we known what LP little a was then and how to test it, those people would have had elevated levels. Had we known what LP little a was then and how to test it, those people would have had elevated levels. So the future of LP little a is going to be very contingent on probably large, you know tens to hundreds of thousands of people being in these trials. And if everyone gets tested for it, we're going to have a lot of, a lot of easier time filling those trials.
Speaker 2:
Absolutely. Yeah, spreading the word is extremely important and, as you point out, there are major cardiac outcome trials that are ongoing as we speak and we need to get people involved. So the physician community needs to listen to what you're saying and hopefully refer patients who are at very high risk for these trials to see if lowering LPA makes a difference. There's still a debate about that. We all know it's a very important risk factor, but just because something is an important risk factor doesn't mean that by reducing it you're going to change the risk profile, and these trials are extraordinarily important to prove that one way or another. Getting a little technical, the trials that we're doing now here that we are enrolling for involves something called small interfering RNA, which is another quote, genetically based way of preventing the assembly of lipoprotein little a, and it involves something called the RNA induced silencing complex, which is part of all the cells that's actually trained to look for pieces of genetic material that can cause problems. It's sort of an intrinsic mechanism of cells to prevent viruses from doing damage, so they're looking for sort of bad pieces of genetic material, and we can train these parts of the cells to identify the strands that are important for making lipoprotein little a and with this technology it seems incredibly safe. So far we're able to reduce levels of LPA by up to 95%, as mentioned. So the next step is to see whether that huge reduction in LPA will translate into fewer heart attacks and strokes for people at extremely high risk.
Speaker 2:
So, again, your comments are well taken, dennis, and you know spreading the word to doctors and patients and getting people involved in these studies is so essentially important for us to progress medicine forward.
Speaker 2:
So I'm going to end with one last notion, and I'm curious to see what your experiences are with this. I'm curious to see what your experiences are with this. So one of the theories about LPA is that it also is a lipoprotein particle that can induce calcification, and it may be particularly associated with aortic stenosis, which is certainly a condition that you've worked with as an interventional cardiologist and for the other people out there, aortic stenosis is when the aortic valve, which is the valve between the left ventricle and the aorta, gets blocked up, typically due to calcium buildup, and there's a theory that lipoprotein little a, particularly at high levels, and maybe particularly certain isoforms, can lead to this aggressive calcification. But in your case you mentioned that earlier in life you didn't have much calcification, but in your case you mentioned that earlier in life you didn't have much calcification, so maybe you can share your thoughts about this interesting theory and where you stand on that.
Speaker 1:
Yeah, I think the connection with calcific aortic stenosis is pretty well established. I mean, it's really it. Not only is that there's a higher incidence of it, but there's a more rapid progression of valvular disease to the point where you need to intervene. And so it's extremely important again that everyone know their LP to lay low, because if they develop a murmur that's preferable to the aortic valve, their doctors need to know that because they need to be followed very carefully for that, because they're likely to have much more rapid progression to it. And there's, of course, a small incidence of sudden death in people with aortic stenosis who hadn't recognized they had the problem and it probably would have been a preventable event.
Speaker 1:
But I think you know the thing about the negative calcium score for me was really a real. It was really confounding or confusing to me about how that could be, how I could have as much vascular disease and plaque that hadn't calcified. Because you think, well, if it calcifies in the aortic valve, why is that calcifying in the artery? So I don't know quite what to make of that, but I think the aortic stenosis story is quite important clinically, have you?
Speaker 2:
had issues with aortic valvulosis.
Speaker 1:
I don't have any issues there.
Speaker 2:
Yeah, that's interesting.
Speaker 2:
We don't understand exactly why certain people are more prone to calcification of the valves and others aren't, but LPA may be a very important piece of the story.
Speaker 2:
But LPA may be a very important piece of the story and, as we speak, clinical trials are contemplating intervening for people with aortic stenosis to see if the reduction of LPA can actually make a difference, and it's another area of research that we'll keep a close eye out for and has a great deal of promise in terms of dealing with a condition that really doesn't have any medical treatment at this point. So, dennis, I can't thank you enough for this just incredible sharing of information and being so forthright telling us your personal details. Thank you so much for sharing that with the audience, and I know this will have a big impact on a lot, lot of lives, in my opinion. Down the road, and also keep up the good work and just talk about research, because, again, the answer to the questions in medicine that are confounding us is through research, and the more support we get of it, the better the public health will be in the future. So many, many thanks, my pleasure.
Speaker 1:
Any concluding remarks? No, again, the bandwagon I'm on is universal testing. I really think there is absolutely no reason that not every person in the United States should be tested once for this problem. Again, it's one in five people who will be identified as being at increased risk for having the vascular and valvular problems associated with it. So the earlier you're identified the better, and you'll become available for being in clinical trials or treatment if you need it, long before the consequences come to bear. Because once you start having those consequences as evidenced in my history you're really off to the races, and if this could be short-circuited 15 years before that, it would be pretty impressive.
Speaker 2:
Well, amen to that and again, many, many thanks for your participation and your contributions to MedEvidence. Thanks, thank you.
Speaker 1:
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