Recorded on January 22, 2025. This transcript has been edited for clarity.
Robert A. Harrington, MD: Hi. This is Bob Harrington from Weill Cornell Medicine in New York City, here on theheart.org | Medscape Cardiology. This is one of my favorite shows of the year. We usually do it at the end of the year, but now we're doing it at the beginning of the year. Today we’ll look back at some of the key cardiology trials and some of the happenings in cardiovascular medicine in 2024, and then look ahead to 2025.
Joining me is my longtime friend and collaborator, Dr Mike Gibson. Mike is a professor of medicine at Harvard Medical School. He's an interventional cardiologist at the Beth Israel Lahey Medical Center in Boston, and he is the CEO of the Baim Institute, an academic research organization. Mike, thanks for joining us here on Medscape Cardiology for our wrap-up/look-ahead show.
C. Michael Gibson, MD: Welcome to 45 times 45: 2025
Beta-Blockers Post-MI
Harrington: I like that. I thought we'd break the show into two parts. First, let's do some of the key trials that set the theme for the big things we learned in 2024. Then we'll turn our attention in the second half of the show to what's ahead. We'll think about science but also policy effects on research.
The number-one trial that I want to talk about is REDUCE-AMI. This was a really interesting trial, Mike, in that it took an old concept, something that we had done for years, which is that post-myocardial infarction, everyone had to get a beta-blocker. The question they tested is, is that still true? What did you think
Gibson: It was true when we were fellows, but I don't think it's necessarily true in 2024 and beyond. There was really no difference in the clinical outcome. But keep in mind that this was a mix of ST elevation myocardial infarction (STEMI) and non-STEMI.
Harrington: They mostly had pretty good ejection fractions (EFs).
Gibson: Yes, EFs of 50% or higher, so this does not apply to those patients who have an EF under 50%. Around 65% were non-STEMI. The other thing that was somewhat discouraging is that it was an open-label study. That's a theme of some of the trials we're going to talk about today, which makes me a little concerned. And it was a little underpowered; they were expecting about a 6% annual event rate but had about a 3% annual event rate. They really didn't hit the numbers they thought they would. It’s important to keep those caveats in mind. Another thing that struck me was that they really underenrolled women. That's a problem we see in a lot of our post-MI studies.
Harrington: You and I have talked about this a lot, particularly with our mutual friend, Roxana Mehran, MD. You can't just assume that things that work in men are going to work in women or vice versa. You and I are involved in a bunch of trials where we've struggled to make sure that we have adequate enrollment of women
What are you doing in practice now, Mike? You still do acute angioplasty call, etc. Are you no longer loading them up with beta-blockers because of trials like this?
Gibson: My practice has definitely changed, particularly in this group of people with EFs over 50%. But again, for the low-EF people who have some heart failure, these results do not apply.
Adding vs Replacing Drugs
Harrington: Another theme that emerged from last year is thinking about older trials, older practices — when do you have to update things? I was talking to somebody recently about bypass surgery and making the point that the trials where we demonstrated the benefit of coronary artery bypass grafting (CABG) in left main disease are really old, with essentially no medical therapy. What does that mean for contemporary medical practice? It gets us to that question of the continuous cycle of evidence generation, and we just don't have that.
Gibson: We don't have that. What we do is we add medicines on top of other old drugs. Aspirin is the classic example. We had aspirin, then we had clopidogrel, which was better than aspirin. We added clopidogrel to aspirin rather than replacing aspirin. Fast-forward 20 years later, and we can now see that a thienopyridine probably is superior to aspirin plus the thienopyridine. We have to reassess as we have new strategies, and we need to be able to replace things.
Harrington: You and I are involved with a clinical trial looking at a factor XI inhibitor, and we're definitely adding there, aren't we? If you're on an antiplatelet, even if you're on dual antiplatelet therapy (DAPT), it doesn't matter; we're going to enroll you. Wouldn't you like to know, is it an anticoagulant, is it an antiplatelet, or is it both? That's really the question that you'd like to answer.
Gibson: I'm disappointed. We’ve had years of studies now where less is more, you get less bleeding, and it doesn't really put you at ischemic risk. But here's the crazy thing: We still have 95% of people getting DAPT through a year. The guidelines have to keep up as well.
Preventive Stenting?
Harrington: When we were planning this particular trial, we agonized over the notion of how many people are going to be on DAPT. How long are they going to be on it? People who participate in clinical trials are a pretty sophisticated group of clinicians, and still, we're seeing a lot of DAPT use.
Let’s move to another old idea, although we have new methods for looking at it, and that's the PREVENT trial. You remember Rick Kuntz’s idea, to stent the entire artery as a way to prevent future coronary events. And people said, “No, you don't want to do that.” He had some elegant angiogram data that suggested that might be the thing to do.
Gibson: That elegant angiogram data came from yours truly. We measured the distance from the ostium down to the stenosis, and most everything is in the first 20% of the vessel that causes a STEMI. You wouldn't have to stent the whole vessel; you may just have to stent that very vulnerable region, which turns out to be the proximal part of vessels. This study took about 1600 people who had a plaque burden greater than 70%; they couldn't have flow-limiting stenosis.
Harrington: They had to do fractional flow reserve (FFR).
Gibson: They had to do FFR, they had to be lipid rich. This was done in the Asian countries which do a lot of intracoronary imaging. This may not apply to the US, where we don't do as much of this imaging. It’s not just a stenting strategy.
Harrington: It’s combining the imaging with the procedural strategy.
Gibson: And it's people who are very good at imaging. The other thing about Asia is they have a lot of fish consumption. The fish gives them the omega fatty acids that have a little bit of an antiplatelet effect. For reasons we don't understand, stent thrombosis is less frequent in Asia. They had very good results. There was about a 10-fold reduction in events, from 3.4% to 0.4% — that's very good. Maybe not as big a relative risk reduction, but similar absolute reduction a few years later. It’s provocative. I submitted many grants to do this years ago. No one would fund it, but it makes you wonder: Are we replacing vulnerable plaque with some stable plaque with this approach?
Harrington: The other thing to note is, yes, it's intraprocedural imaging, but now CT imaging, CT angiography, photon CT is getting to be a powerful technology to look at plaque noninvasively. Maybe we can start to quantify how much vulnerability there is in this plaque, or even get a noninvasive equivalent to FFR. If you get data on the flow, the plaque characteristics, then maybe you can go in there and stent in a very directed way.
Gibson: Absolutely. The leaders in this field are using AI to characterize the plaque constituency: Is it fatty or not? Knowing that, we can do spot stenting. It's a wonderful hypothesis.
Harrington: It's worth testing, isn't it? The other thing is that when you and Rick and others proposed these notions years ago, we had a very different type of stenting platform. Now we have much thinner stents, less risk for stent thrombosis, better antiplatelet therapy.
Gibson: In this trial, 33% were bioresorbable stents.
Harrington: But didn't it look like the metal stents were better than the bioabsorbable stents?
Gibson: It depends. Early on, the bioresorbables had a little bit of a hazard, but a couple years later, the curves inverted so they did better late, which is what you would hypothesize; because once it's gone, you should have normal vessel there. That may be a normal-functioning vessel which would be pretty good over the long haul. One other caveat is that this trial was unblinded and the endpoint was driven a lot by revascularization.
GLP-1s and the Public Health Implications
Harrington: It’s a theme, isn't it? This unblinded nature in a device trial is always problematic. It gets into the whole issue of shams. It opens up a lot of questions in clinical study design.
Mike, let's move away from a specific study and talk about an area that you and I did a TCT session on, and that’s GLP-1s. It's like the era where every statin trial seemed to teach us something new. Now we're seeing this with GLP-1s, and wow. What's your sense?
Gibson: We have a lot of diseases: atrial fibrillation (AF), hypertension, diabetes, arthritis, and they're part of a syndrome. That syndrome is called obesity. I'm going to go out on a limb and say that I think this is going to be amazing for public health.
Harrington: Wow, that is a big statement. So you're putting it up there with big changes in in public health.
Gibson: This is a disease of lifestyle. It's a disease of 40-60 years of being obese. We talked about LDL-C years; I think someday we're going to be talking about pound years or BMI years. This is a cumulative effect of this syndrome. We’re also going to change from viewing it as a moral failing to a complex disease. The results are all consistent. But what's fascinating is the mechanisms, and some of this is probably going to be mediated centrally by dopamine and positive feedback loops.
I'll be honest: I took them, I lost 30 pounds, and I kept the weight off. All my numbers came down. My LDL-C is 27 mg/dL now with different drugs. Your HbA1c comes down, your blood pressure. People wonder why the curves diverge so early. They're diverging early because you're treating every single modifiable risk factor, maybe even smoking, because some people stop smoking.
Harrington: Not just smoking. People stop consuming as much alcohol. They stop gambling.
Gibson: I didn't drink much before, but I don't drink at all now. It's fascinating; you just have no desire for those types of things. I think it's going to be revolutionary. What's fascinating is that the battle of the marketplace seems to be over who can get a 25% weight reduction. And if you don't hit 25%, you're kind of dead in the water.
Harrington: Yeah, a recent trial missed 25%, and even though it looks like an impressively positive clinical trial, the criticism was just as you said — that it didn't hit 25%. So, what does that mean?
Gibson: Do we need 25%? Well, maybe in the induction phase. But what's being ignored is the maintenance phase. And there it may be a whole different ball game. What we want there is tolerability, no side effects. You don't need to keep losing 25% of your body weight. It's going to be interesting to see how things shake out. I think the side effects are going to be a big driver of clinical success.
Harrington: People have been talking about this on-ramping and off-ramping; you're calling it induction and chronic maintenance. It brings into cardiovascular medicine some of the lingo of cancer drugs, doesn't it? And in addition to the GI side effects, there’s also skeletal muscle loss that people are concerned about.
Gibson: It's a little confusing. You have a little fat in your muscles, and if you lose fat, the fat between the muscle cells goes away too. The real question is about muscle function. Muscle function seems to be pretty well preserved, but there's a little bit of data both ways, so that's still playing out.
Lower Is Better for Blood Pressure
Harrington: We've got to figure it out, but certainly, let's keep an eye on the class. I suspect that as you and I look ahead in 2025, this will be a topic we revisit.
The next trial is BPROAD, which I liked as somebody interested in public health, big global problems — because blood pressure remains a global problem. This was a large clinical trial done in China that asked a very simple question: Is an intermediate level of blood pressure control as good as really tight blood pressure control of less than 120 mm Hg? What did you think of that?
Gibson: A big trial, about 12,000 patients, and about 6000 randomized to getting it down below 120 mm Hg and another 6000 randomized to below 140 mm Hg. Getting it down to 120 mm Hg gave you about a 25% risk reduction, and that makes sense. There's a U-shaped curve. To be sure, lower is not always better, but getting to that kind of set point — around 120 to 100 — looks like it's a good idea.
Harrington: It really does, doesn't it? It was great to see this trial coming out of China, where blood pressure is a really big issue and contributes to a lot of morbidity and mortality, particularly through stroke. It's been said that if you really want to change global public health quickly, control the globe's blood pressure and get rid of tobacco. Do those two things and you have a major influence on global public health.
Now these are specifically people with diabetes, but most of us would say that this applies broadly. Let's get blood pressure lower. Your point's well taken; you don't want to go so low that you're dizzy, falling, having the complications of that. But you want to go low.
Gibson: There were more people who had some symptomatic hypotension, a little more hyperkalemia. I think those things can be managed. Again, the theme here is open-label study. That was disappointing to see.
TAVR in Asymptomatic Aortic Stenosis
Harrington: Particularly a trial like this. We know how to blind these things. There is an expense but it can be done. It can be masked. There are ways to do this.
There are two more trials that I want to cover. First is EARLY TAVR. You made reference to how difficult it can be when trials of devices are not blinded. We talked about a strategy in PREVENT, and here we're talking about a strategy. If you had severe but asymptomatic aortic stenosis, you got randomized to immediate or early transcatheter aortic valve replacement (TAVR), vs TAVR only if you needed one, so to speak. The trial was positive from the primary endpoint. But a big criticism was that the primary endpoint included unplanned hospitalization, and 50% or so of people in the deferred arm or the surveillance arm ended up getting TAVR within the first year. What did we learn here, Mike?
Gibson: First of all, no difference in death. Numerically, a few fewer strokes in the early-TAVR arm, but it didn't significantly differ. But this is what happens in these kinds of studies. Is an early TAVR better than a late one? And when the endpoint is that you got a TAVR or were hospitalized, it kind of dilutes our understanding even of the timing of the benefit. Unblinded — it wasn't a sham-controlled trial, but it looks like it's reasonable to intervene early.
Harrington: Another criticism from several people was about the lack of a surgical arm. What do you think of that?
Gibson: Well, that's very true. If you're getting a TAVR and it's a matter of when,… But they didn't compare it to surgery. The other question is the durability. The follow-up wasn't that long, and you may have better durability with a surgical approach. So that's a good criticism. And also derivation is another limitation,
Harrington: If you're going to have surgery as an arm, then you have to have longer follow-up. The classic example is the early CABG trials. If you only compared things at 30 days, CABG loses. It’s the durability over time that really makes the difference. It is too bad they didn't have a surgical arm. But certainly it's intriguing that maybe earlier is better.
Gibson: We're doing a bad job on long-term follow-up of these devices. And I'm proud to say that here at Baim, we have developed a registry. We've completed building it so that we can follow people up to 5, 10, 20 years. We're going to go direct to patient. We're finding that people will fill out these forms. So we've built it so they get randomized. You'll be able to get followed up every year all the way up through 20 years so that we can get long-term data.
Harrington: It’s interesting that during COVID, when we all got our vaccines, we were being tracked by our iPhones, right? I would get a message saying, "Hey, can you provide us a little bit of data?" And I find that most people who have had a medical procedure, who are on a therapy, who have some syndrome, they're happy to give you their data, as long as you can tell them that it's going to be used for something meaningful.
Gibson: We were dumbfounded in the Apple study that the reason people participated was altruism.
Factor XI Inhibitors
Harrington: Last trial before we turn to 2025, Mike: OCEANIC-AF. Again, I'll note the conflict for both of us. You and I are involved with a series of clinical trials with another factor XI inhibitor that are still ongoing, including in the AF space. OCEANIC-AF was an interesting study done with the factor XI inhibitor asundexian, and was presented at the ESC meeting last summer. The trial was actually stopped early by its data and safety monitoring board because there was an increased risk for stroke in the factor XI inhibitor-treated group compared with the apixaban-treated group. Is this a class effect? Is this a specific drug effect? Was this a dosing issue? What is this?
Gibson: I do receive grant support from every manufacturer of factor XI inhibitors, and I wrote an editorial about this in JACC. What went wrong? Is it the wrong hypothesis, wrong dose, wrong patient?
In terms of the wrong hypothesis, when you measured the factor XI levels, the people with and without an event — at least, using the Bayer assay — did not differ. That makes you wonder, is there anything related to the factor XI levels? There were very small numbers of patients with events in the assay substudy.
Was it the wrong dose? The dose is 50 mg of asundexian once a day, with high peaks and low troughs. How will that compare with twice-a-day dosing of milvexian, where you have slightly lower peaks but higher troughs at a four-times-higher dose? We'll test the hypothesis. We don't know yet.
Was it the wrong patients? To be honest, Bob, if you're tolerating apixaban and have been for years, how are we going to reduce bleeding? That seems like a stretch goal. There was a substudy that showed that the real difference was in those people naive to anticoagulation. That's a big unanswered question.
Harrington: Still a lot of unanswered questions. My personal nickel down has been on the dosing issue. One of the things we know about the drug that you and I are both working with (milvexian) is that it prevents clot at the doses that were studied, because there was the classic DVT study in the total knee replacement patient. Those data have been published. We’re making a lot of indirect comparisons here. The trial of milvexian in AF is still ongoing. The hypothesis is out there and being tested, and we'll see in the years ahead.
2025 and the Battle With Misinformation
Harrington: Let's switch to 2025. Obviously, a new administration in Washington. New leaders of the FDA, new leaders of the NIH, of the CDC, of CMS — all the agencies that affect the lives of those of us working in healthcare, science, and biomedicine. You run a research institute. You're a practitioner. What are you thinking about?
Gibson: Well, first of all, I'd like to say thank you to the outgoing FDA Commissioner, Rob Califf, who did an amazing job, coming back for a second term. It’s a thankless job. Rob and I talked a lot about one of the biggest problems, and that is misinformation. It's something we've got to really tackle head-on. It's a very tough issue. I've been on the phone with several cardiovascular societies about this issue. There's a balance: If you shut things down and don't give people a voice, that's not a good idea; if you make it a democratized approach, well, there will be misinformation.
The question is, how do you counter that? Do you quiet voices or do you allow greater voices to overcome the misinformation? I was naive when, 20 years ago, I created wikidoc, an open-source textbook. I thought, Let’s give everyone a voice. Democratization of information — this is going to be great. Well, I was naive. There are plenty of people out there who will put up the wrong information.
Harrington: There are some bad actors out there.
Gibson: There are bad actors. I've come to understand that the wisdom of the crowd isn't always wise, because you have some very loud people who may not always be right. Sometimes they're right, but sometimes they're not. We have to have curation of medical knowledge. I think that's why we still need experts, but we need debate.
The other thing doctors are very concerned about is their safety on social media sites. I'm here today to announce for the first time publicly that we have built a Twitter clone. We're planning to release it around the time of ACC. It will be largely for healthcare professionals or people interested in healthcare. It's going to be a little different to Twitter. You're going to say who you are and what you're interested in — eg, "I'm a cardiologist." Then you specify who you’d like to talk to, and you could say patients, other cardiologists, regulators. Then you specify who you want to hear from — other cardiologists or whoever. That way, you can filter who your voice goes to and also who you are listening to. Our tagline is "Going from credibility to care." We want to have credible information. We want to hear voices, but we want to make sure that we're vetting things. We will have some light moderation, but we're going to welcome everyone to that community. People are leaving Twitter (X) and going to Bluesky. That's a general platform, but we think it's time to have a platform dedicated to healthcare professionals,
Harrington: Is it healthcare and science?
Gibson: Yes, because those two go together. I also want to say a word about AI. I'm very concerned about AI. I would urge everyone to read the book Nexus by Harari. Here's the premise: We are storytellers, and the best storytellers prevail. You don't even have to see the person; you can just be told a story virtually and it can be very powerful.
The problem is that I think ChatGPT is going to largely replace textbooks. I write a big textbook and I can see that when I use ChatGPT, the answers are pretty good diagnostically. But on the treatment side, ChatGPT doesn't really get it right. We don't know why it's spitting out the wrong answer. We don't know how or where to intercede to get it to the right answer. How do you tell ChatGPT, "No, no, the guidelines say this, not that"? We're going to need better approaches to the treatment side of AI and some human curation.
Harrington: I'm excited to explore your new social media offering. I want to make sure that I continue to do a couple of things: I've stayed on X. I've opened a Bluesky account. I haven't posted because I don't want to just be surrounded by voices that agree with me. I want to be surrounded by different types of voices. You know, one of the beauties of Twitter in the early days is it introduced me to a lot of people that I had never met before who often had opinions contrary to mine, and that was exciting. That was interesting. I learned a lot.
For me, the reason I’ve lost interest in X is the complete lack of civility of some people. I don't mind being criticized. You and I debate things all the time, but we do it in a professional, civil, respectful way. The way that some people address others on X, it's just wrong. That lack of civility really bothers me, and maybe that's what you're referring to in terms of light moderation.
You mentioned our mutual friend, Dr Califf. Longtime listeners know that you and I are old friends of Dr Califf. For a guy that gave up what he was doing to take on this public service role, the vitriol that's heaped upon him really pained me. Hey, I don't agree with him all the time, and I'd love to debate him about some of those things, but I know that he's a smart, data-driven, high-moral-value guy. To read the garbage from some people out there is really bothersome. It's disturbing. And I hope that in a platform for professionals, Mike, people will act professionally.
Gibson: I agree. I didn't leave X and I'm not going to leave X.
Harrington: Nor am I.
Gibson: The data are the data, and let's stick to the data. I love debating the data. I'm a professional debater, but I don't think we should go into personal attacks. That really doesn't have a place. I get attacked a lot. I just let it roll off my back. But for some other people, it's really upsetting.
Harrington: Are we going to see this by the ACC? Fantastic. Can I book the handle heartBobH?
Gibson: I reserved it for you.
RFK Jr's Focus on Health and Prevention
Harrington: A couple more things. The nominee for HHS Secretary, Mr Kennedy, is talking about focusing the country's attention on health and prevention, as opposed to disease, or in addition to disease — not a bad idea. We talked in our last segment about GLP-1s and the intersection of obesity with all these diseases. That's something I'm certainly behind. A focus on the preventable diseases: heart disease, the inflammatory disorders, cancer. It’s important stuff.
Gibson: I agree. Here's the problem, though, Bob. I've been training in the wellness space with wellness apps, and wellness is kind of boring. So how do you engage people who are well? That's one of the big challenges. The approaches that are most successful are gamification. Here's your step count today. Here are your calories, your metrics. Here's a leaderboard. How do you compare with everyone else? When you look at the metrics of who's engaged, it's the gamification and those rewards that seem to really be important.
Harrington: I'm a big Peloton rider. I'm competitive. I like to look at my data and compare it to people that I'm competing against that day. We like that behavioral feedback as human beings.
Gibson: A lot of this comes down to behavioral modification. You know, it's not science. A lot of it is policy. The other thing is, when it comes to wellness and even sickness, we're really going direct to the patient. And patients want that. They don't want to come in, they don't want to park, they want to do as much as they can virtually. They want to manage their health frequently on a call. You're going to see a lot of efforts toward empowering patients, giving them those metrics. The wearables are unbelievable. Now there's a company, Binah.ai, that can measure pulse, blood pressure, cardiac output, cholesterol, LDL, glucose, HbA1c, CRP, leukocyte count. It's all going to be on a ring. We’re going to see an explosion in the management of that data. But the real thing is that engagement.
Harrington: You and I are involved with some of the wearables, both from a consulting perspective but also from a research perspective. There was a company a few years ago at the AHA health technology forum, and they were talking about a wearable that can measure troponin. You and I are involved with a wearable 12-lead EKG, derived through vector cardiography. You get your 12-lead EKG, your troponin, you have symptoms — wow, diagnosis at home, helping us with that probabilistic examination that goes on every time you ask, “Well, does it sound like angina? Did you have angina in the past? Do you have any known coronary disease? What does your EKG look like? What's your troponin look like?” This potentially makes it a lot easier, doesn't it?
Gibson: A couple years ago, I published a single-lead EKG, AI detection 95% accuracy of a STEMI. So if we can get down to a single lead and spit in a cup or a wearable to look at your troponin… The other key thing is getting away from the word "STEMI" and getting to "occluded MI."
Harrington: Yes, you and I, with Manesh Patel, did a podcast on the remarkable work that some folks have been doing to help us decide if the arteries are occluded or not. I'm with you, Mike. I thought that was a fabulous discussion. And the post-show pickup on social media was also great to see because people were interested in the question.
Gibson: But that's where I do think, AI and machine learning will come in handy.
Harrington: This has been a fabulous conversation. I want to thank you for a look back at 2024 and, maybe more interestingly, a look forward into 2025. We covered a lot of ground. My guest today on theheart.org | Medscape Cardiology has been Mike Gibson from Harvard. He's an interventional cardiologist at the Beth Israel Lahey, and he's the CEO of Baim Institute. Mike, thanks for joining me here on Medscape Cardiology.
Gibson: Thanks for having me — my favorite day of the year.
Harrington: And finally, I want to thank you, the audience, for tuning in. If you like this podcast, please take a moment to like, subscribe, or even write a review. It helps others discover the show. We want feedback — positive or negative — and suggestions for future guests and topics to cover with people like Mike. Thanks for listening.
Robert A. Harrington, MD, is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, as well as a former president of the American Heart Association. He cares deeply about the generation of evidence to guide clinical practice. When not focusing on medicine, Harrington dreams of being a radio commentator for the Boston Red Sox.
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Cite this: Cardiology 2024 Highlights and Predictions for 2025 - Medscape - Jan 30, 2025.
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