Cardiovascular Medicine 2025 Wrapped: The Big Picture

This transcript has been edited for clarity.

Robert A. Harrington, MD: Hi. I’m Bob Harrington from Weill Cornell Medicine here in New York City, and recording my favorite podcast of the year, which is the cardiology year in review, with my good friend Mike Gibson. We’ve done this for a number of years now. Mike is an interventional cardiologist in Boston. He is the CEO of the not-for-profit academic research organization the Baim Institute, and Mike is also a professor of medicine at Harvard Medical School. Mike, thanks for joining us here on Medscape Cardiology | theheart.org.

C. Michael Gibson, MD: It must be the holiday season. This is how I know it’s the end of the year.

Harrington: Well, Mike, I don’t know if you noticed, but I’m wearing my holiday shirt for the holiday season. You and I are going to try to bring good cheer to all in cardiovascular medicine.

My most memorable event of the last few years is when you struck the Heisman pose on this podcast, reflecting your University of Chicago football roots, so you never know. We may give some trial the Heisman this year, and you’ll have to dust it off.

On a serious note, this has been a tough time in academic medicine. It’s been a tough time in higher ed over the course of the year. There have been challenges with NIH funding — certainly at our own place, that was a big issue — and challenges at the FDA, which a lot of us are watching carefully because of the important cardiovascular drugs moving through the system. Just a tough year, but let’s try to summarize some of the important, interesting, and maybe even impactful things that are going on in cardiovascular medicine.

In the past, what we’ve done is, I’ll throw out a trial. You’ll describe the trial. We’ll talk about the implications. Then we reverse roles. How about this year, we focus on what I’ll call the big picture. What are the things that you and I have both found interesting, potentially impactful, forward-thinking, and maybe some things to pay attention to in 2026?

How does that sound?

Gibson: Sounds great.

New Acute Coronary Syndrome Guidelines

Harrington: The first one I want to talk about is the acute coronary syndrome (ACS) guidelines that came out in February 2025. Our mutual friend Sunil Rao from NYU was the lead author on that terrific document. You and I have been involved in ACS research for more than three decades now, it’s not getting any simpler, is it?

Gibson: It is not getting any simpler. We have a lot of recommendations about devices now. In the past, there was a lot of discussion about drugs, but we’re starting to see more recommendations about dilating those severe nonculprit arteries if the patient doesn’t have cardiogenic shock. We saw a recommendation for microaxial support in people with shock. Now that’s different from what we’ve seen in the past for balloon pumps or extracorporeal membrane oxygenation (ECMO). And there was some imaging stuff. Intravascular ultrasound (IVUS) has an indication now for better outcomes in ACS patients; that’s a new entry into the field.

The most interesting drug information is about dual antiplatelet therapy (DAPT). In this guideline, we start to see the elevation of ticagrelor and prasugrel over clopidogrel. What did not make it into the guidelines is the couple of prize fights we’ve had between prasugrel and ticagrelor with prasugrel prevailing twice now. But that did not make it into this guideline.

One of the biggest questions is the optimal duration of DAPT after ACS. The default mode was 1 year, and from the trials, still 95% of people are getting a year of DAPT. I would have thought the transition to monotherapy would be happening more often. We’re not seeing that in practice.

One year is the default recommendation in the ACS guidelines. However, there is now a recommendation for early transition to ticagrelor monotherapy after over a month. That’s new. It does give permission to people who want to do that in their patients with high bleeding risk, and if they’re on an oral anticoagulant an even earlier transition may be better — they say greater than a week, although I tend to be a 1- month kind of person. I have to be honest, I’ve been a little skeptical of some of these early transition trials, many of them done in Asia.

The quality of the trial is exceptional. That’s not the issue. The issue is that they do a lot of things there that we don’t do routinely here. They do a lot of intravascular imaging. They really optimize their outcomes, so their results may not apply to the rest of us.

Another real problem I have is that the trials that are using net adverse clinical events endpoints combining ischemia and bleeding together. Ischemia should be analyzed by intention to treat; bleeding should be analyzed as treated. It’s not a good idea to put them together.

Finally, regulators and trialists like myself do not recommend endpoints that go in opposite directions being put together when you are assessing a noninferiority outcome. And that’s a lot of what’s been going on. What are your thoughts?

Harrington:, You’ve hit some of the key points for me. Earlier this year, I was giving a presentation on the new ACS guidelines and used the opportunity to go back to the beginning. The unstable angina, non-Q-wave infarction guideline was one of the first guidelines. It was commissioned by the Agency for Healthcare Research and Quality at the time, and a lot of the work had been done by Dan Mark, Bob Jones, Rob Califf, and others at Duke. You go back to those early guidelines, and it’s heparin at really high doses, aspirin at doses that we weren’t sure of, and not a lot else in terms of antithrombotic therapy. And now fast-forward 35-plus years, and we have not just a whole suite of drugs, but we also have different strategies.

One thing that strikes me most about the ACS guidelines is that it’s all about strategies. There’s not a lot of new drugs in the arena of ACS. We’re still tussling it out: Is drug A better than drug B, etc? What we’re really struggling with, and I think this reflects the complexity of practice, is the different strategies. There’s a chart in the guidelines, which has the default strategy of antiplatelet therapy, the bleeding reduction strategy, and the high bleeding risk strategy. The number of strategy trials that have been done is really extraordinary, but yet, as you and I have observed, it looks like most people are adhering to the default strategy of 12 months of DAPT.

We’ve got to figure out how to communicate the accruing new evidence to the practicing clinicians, and how we think about going forward. The prasugrel vs ticagrelor story is a good one. They were developed in very different ways. One of them was in all-comers with ticagrelor. I was involved with the PLATO study. You were involved with the TRITON-TIMI 38 study with prasugrel. These were very different trial designs, and only now, years later, are we starting to see them compared head to head. We need more of that as drugs of the same class make their way onto the market.

Gibson: The other thing is, we lived through an era of accretion. We just kept adding drugs on and on; there’s no subtraction. We need to start replacing drugs rather than adding on drugs.

Aspirin Withdrawal The Good and The Bad

Harrington: There are two trials that I want you to comment on, Mike, because they deal with the withdrawal aspect. Over the years of designing trials in acute coronary disease, nobody would dare take away aspirin. That was foundational. Everybody had to be on aspirin, and then you could add stuff. But now we’ve got the NEO-MINDSET trial done in Brazil, where aspirin was withdrawn within four days after percutaneous coronary intervention. That didn’t turn out to be such a good idea.

Gibson: No. You’ve got to be careful, right? This is a balancing act. You want to balance bleeding and ischemia. If you fall off on either side, it’s bad. Perhaps a year of DAPT is too long, but it’s looking like just a few days is too short. I think a month is about the right duration in a lot of settings. For aspirin, you use the word “foundational,” but we knew 30 years ago that clopidogrel may be a better foundation as a more potent antiplatelet than aspirin. Now we’re just getting around to showing that aspirin may not add that much to the thienopyridines. In the old days, we asked, do the thienopyridines add anything to aspirin?

Harrington: That’s right. And does aspirin add to chronic anticoagulation? One of my most interesting trials of the year was AQUATIC. When you added aspirin, people did worse.

Gibson: We always see that bleeding and efficacy are related to each other, in ways that may not be clear. The more you bleed, oftentimes, the worse the efficacy signal. And that may be because you stop other lifesaving medicines. A patient may say, I don’t know which drug is causing this bleeding, but I’m going to stop the pink one, the green one, and the yellow one. And they fall off the track of evidence-based medicine, or they may have intraplaque hemorrhage. It’s very complicated.

Harrington: It’s very complicated. If you think about the complexity of the guidelines, we should get help from tools like artificial intelligence (AI), because of the ability to synthesize a lot more data quickly. If we can start embedding some of these AI agents into our own medical records, etc, and begin to think in terms of the patient’s phenotype and these other characteristics — what are all the supporting pieces of data that would say prolonged antiplatelet therapy, shortened dual antiplatelet therapy, a different regimen? I think we’re going to get there. What’s the number you get if you add up all the combinations and permutations in acute coronary disease of antithrombotic therapy?

Gibson: It’s 2.7 million. That’s why the mind is boggled; it can’t do it. That’s where AI may help. I just presented, at the Global CVCT Forum, a paper on using AI to do what we should be doing as clinicians.

Patients don’t care about populations. They want to know, what’s going to happen to me? They also want to know their iterative risk. If you have a gastrointestinal (GI) bleed or a stroke, your risk is different moving forward. If nothing bad happens while you’re on an anticoagulant, you’ve passed the bleeding stress test, we need to be iteratively assessing risk at all moments in time to make adjustments. Then, some patients value ischemia differently than bleeding.

We took people’s ranking of ischemic outcomes and bleeding outcomes with that iterative monthly risk assessment, so that in all moments in time, you could sit with a patient and move the dial on their screen of how they’re feeling about disability, death, ischemic stroke, and major GI bleed. Then it tells you, given your preferences, here’s the anticoagulant dose: is it 15 mg, 30 mg, or 60 mg of edoxaban that maximizes what you as an individual patient wants? I think that’s where we’re going: individualized, shared decision-making powered not by bleeding risk scores, but by your risk and your preferences, not population preferences about bleeding and ischemia.

Harrington: It’s such an important topic, and now that we have some different methods of analyzing data, etc, you made me think of a couple of things. One is that people do value things differently. Years ago, we did a clinical trial with one of the oral glycoprotein IIb/IIIa inhibitors called APLAUD, where we asked people who had had either a stroke or a myocardial infarction (MI) how much bleeding risk they would tolerate in order to continue the drug. And it may not be surprising, but if you were a stroke patient, you were willing to tolerate a lot more bleeding than if you were an MI patient, and that’s because the stroke patients were left with a bit of a disability. They remember not being able to move their arm or having trouble with their speech. The MI patient doesn’t have that same recollection, and so your point of personalization is critical. That’s the first point.

The second is that Paul Armstrong and the Alberta group have talked for years of dynamic risk stratification. Now we actually have better tools to do that. We do that at baseline in the trials because we’re concerned about what happens after you randomize — once you randomize, everything is potentially influenced by the randomized treatment, and so it’s only the baseline assessment that’s free of that bias. But you’re right: We’re going to be able to use population-level data to get at individual decision making.

Gibson: And let’s listen to the patients. We often are paternalistic about our view as doctors; we want to minimize bleeding. I call it the NNB: the number needed to blame, and we don’t want to get blamed. We have to stop that and start listening to what patients want.

Factor IX Inhibitors Mixed

Harrington: I completely agree with you in that, because if you go back to the original Sackett reading of evidence-based medicine, he said it’s putting everything in the context of that individual patient’s values and preferences. We need to bring that spirit back.

Let’s stick to antithrombotic therapy. You and I very involved with the development of a factor XIa inhibitor, milvexian. This has been a busy year for factor XI inhibition. We saw the asundexian factor XI inhibitor OCEANIC-AF trial stop prematurely because of increased harm relative to apixaban — increased risk for stroke. We’ve seen the phase 2 AZALEA-TIMI 71 trial of abelacimab, which suggested that you can get potent factor XI inhibition with an injectable over time with a lot less bleeding. You and I are involved in trials where the data are not yet public, but it has been announced that the ACS trial LIBREXIA-ACS was stopped early for no benefit. Where is factor XI inhibition going? Do you remain bullish? What are we going to see in 2026?

Gibson: Well, certainly the epidemiologic data and the Mendelian randomization data, would suggest there’s a there there, in terms of it being a viable target.

Harrington: And I left out OCEANIC-STROKE, so let’s throw that in there too.

Gibson: On the venous side, the post op, VTE reduction trials have seen positive results. The drugs are working on the venous side. I think we really need to focus on the medically ill populations, something you and I studied in the APEX trial. We might see benefits on the arterial side with the right drug to the right patient at the right time, at the right dose. I think we’ve been having some dosing issues with some of the drugs. Keep in mind, for asundexian there is reporting by press release of a positive trial for stroke — superiority of asundexian over placebo in the setting of stroke. We haven’t seen the results yet. It’s a little tougher when you’re going up against an active comparator, like apixaban. We’ll see pretty soon what kind of benefits they saw in the setting of stroke.

Harrington: We’re looking forward to seeing details on OCEANIC-STROKE. We’re moving forward with milvexian. There’s a stroke trial that is continuing to enroll patients, and the LIBREXIA-AF trial, which is in follow-up, trying to accumulate events over time. So it’s an exciting time. We’re going to know the answer as to the value of and the risks of factor XI inhibition.

GLP-1s a Longevity Drug?

Harrington: Now onto what is probably the hottest topic of the past couple of years, and that’s GLP-1 agonists. Give us the state of the state, Mike.

Gibson: Just this week, we saw a 27%-29%, 71-lb reduction in body weight and improvement in arthritis in some of these patients, and that’s with a triple agonist. So we’re starting to see that we can really ramp up the amount of weight loss. That’s good news. The big battle is going to be over quantity vs quality of weight loss. Is the winner going to be the drugs that allow you to stay on them for longer periods of time to keep the weight off?

Are people going to want a once a day oral, once a week subcutaneously, or once a month subcutaneously with maybe not as much weight loss, but an easier regimen. In the polling I’ve done, people tend to prefer that once-a-month subcutaneous regimen with 10%-15% weight loss. Wall Street tends to reward quantity; I think doctors and patients are probably going to settle in on quality of weight loss, something they can tolerate and keep the pounds off.

Another hot issue is muscle loss. The majority view among the experts is that there is some muscle wasting. Some of that may be because you’re lighter and not carrying around as many pounds. Some experts say that some of the muscle loss is water loss within the muscle. Some of them say, when you do very fine CT scans, the muscle isn’t reduced; it’s the fat between the muscles. There are some myotropic drugs in development, and I’m involved with one of them, that are going to increase or preserve muscle mass. So that’s going to be a hot topic. There are investigational amylin receptor agonists coming along as monotherapy and combinations. Maybe it’ll improve the tolerability of all these drugs. So it is a real hot area with a lot of shots on goal.

I do think this will be one of the most important developments in drug history. When you take these drugs, you’re modifying all of your modifiable risk factors. You’re lowering your low-density lipoprotein cholesterol (LDL-C), you’re lowering A1c, you’re lowering blood pressure. And on top of that, you may stop smoking. We’re reducing every modifiable risk factor and when you do that, you get to Eric Topol’s concept of a longevity drug with all of these weight-loss drugs.

Harrington: I’m glad you mentioned Eric’s book, Super Agers. I had a chance to interview him on this podcast a few months ago. It was one of my top reads this past year. As he does so well in communicating complex topics, Eric calls them the big three: heart disease, cancer, and neurodegenerative diseases.

There’s a common thread both in terms of risk factors, but also mechanistically. These risk factors lead to heightened inflammation, that leads to abnormal immune response. Maybe what we see with the GLP-1s is that you lower that inflammatory response, perhaps through the effect on the risk factors. But there may be other effects that we’re still teasing out. And there may be a unifying theory, if you will, as to the benefit that we’re getting. But clearly, the clinical results are extraordinary.

We could do a whole other show, and maybe we will, on the public policy implications. People are losing weight, having fewer events, etc, but the expense from a societal perspective in the short term is high. Is that going to be outweighed by a cost savings in the healthcare system longer-term, with fewer procedures, etc?

Gibson: Milton Packer has come up with the adipokine hypothesis — that the underlying linkage between so many of these diseases, including heart failure with preserved ejection fraction, is the adipokine axis, and certainly we’re affecting that. Eric did a beautiful job of saying that rather than longevity, we need to be focusing on healthspan. We’re not just trying to add years to someone’s life. We’re trying to add life to those years. It’s really about preserving health later in life, and the best way to do that is to start altering behavior early in life.

Valentin Fuster and others are testing that with early intervention; primordial prevention is going to be important. We know lower is better for cholesterol. We know lower is better with respect to weight. We have cholesterol-years; now we need to start talking about obesity-years or pound-years. Once you hit that 4000 to 5000 number by multiplying your LDL-C by years, you’re going to have symptomatic atherosclerosis. We’re going to need to look at the same thing with weight.

The underlying theme of so much of this as you mentioned is inflammation. Whether it’s exercise, sleep, loneliness, or social isolation, so many of these things are working through the inflammatory axis.

Harrington: In his book, Eric gives a great description of what sleep actually does in terms of allowing our brains to clear out some of those inflammatory molecules. What did the American Heart Association (AHA) add to “life’s simple seven“? Sleep and the health benefits of sleep for “life’s essential eight.”

CRISPR and Getting Lipids Lower for Longer

Harrington: As we get near the end, I want to cover three topics quickly. Gene editing —what happened at Penn this past year with the bespoke CRISPR editing of a baby with a rare metabolic disease, which was absolutely extraordinary from a scientific perspective. That was a really personalized approach to a rare disease, but now we’re starting to see genome editing for lipids. We had a presentation from Steve Nichols at AHA on LDL-C. We’re starting to see it for lipoprotein(a) [Lp(a)] and triglycerides. What’s your view?

Gibson: VERVE first entered into the field with a PCSK9 gene editing approach that had some toxicity and has been put on hold, but they’re going after LDL and Lp(a), as are others.

The other hot things are genetic cardiomyopathies. I’m going to be working with a company on gene editing for dilated cardiomyopathies. They’re going to be some shots on goal for gene editing, for obstructive hypertrophic cardiomyopathy. The future there looks very exciting.

Harrington: I want to do two more trials, one of which involved your colleagues at the TIMI group, and that’s the VESALIUS-CV trial with evolocumab. We know that if you have atherosclerotic coronary disease and have had an event, lowering your LDL via PCSK9 inhibition gives you incremental benefit. Now, this trial shows that lowering it in people who are at risk for but have not yet had an event is a strategy that also looks beneficial. You want to comment on that one?

Gibson: Important results: a 36% reduction in MI if you have some atherosclerosis, but you haven’t had an event yet. There’s millions of people like this out there. So very important results for the PCSK9 inhibitor. Now, if you’re a purist, statistically, you’re going to say the all-cause mortality benefit, doesn’t count, because cardiovascular death didn’t shift, but there was a reduction in all-cause mortality. I think it’s pushing us to say that not only is lower better, but I think the new LDL-C target may be 45 mg/dL — that’s what they drove down to. We’ve got to think not only is lower better, but lower for longer is better.

Harrington: Thinking back to the cholesterol lowering guidelines, where there was always this notion of assessing risk and so much risk was driven by age, we inadvertently pushed the initiation of LDL-C lowering to older ages. We’re now recognizing that it’s the lifetime burden of LDL-C that we need to consider. How do we quantify that; how do we decide when you start therapy? I think you’re going to see that you want to go lower and you want to go lower earlier.

Gibson: My LDL-C is 19 mg/dL on three drugs, I am proud of it. I do believe lower is better, and I wish I’d started earlier.

Harrington: I’m 100% with you. Last one, kudos to you. You and I grew up in the age of the glycoprotein IIb/IIIa inhibitors. We did a lot of the trials in the 1990s into the 2000s. Better drugs have come along, easier to use with less bleeding risk. But you’re revisiting it with our old friend, Barry Coller, who was the discoverer of abciximab. He’s now got a new approach, which is to give an injectable glycoprotein IIb/IIIa inhibitor at the first point of medical contact in people with a suspected MI. You presented a trial called CELEBRATE at the AHA. Give us a celebration.

Gibson: We all worked so hard to get those door-to-balloon times down to 90 minutes. Great job. The problem is our patients are still waiting 2.25 hours to come to the hospital with a heart attack.

Harrington: It hasn’t changed since GUSTO-1.

Gibson: It’s like the atomic clock. It has not changed, and no one’s really been able to crack it. So we said, we’ve got to do something in the home. So we gave a new subcutaneous IIb/IIIa inhibitor in the home, or right when you got in the ambulance, to see if we could get some arteries open earlier and if that would improve outcomes. This is not your 1990s. This is not the femoral access era; we’re now in the era of radial approaches, and we don’t see those femoral and retroperitoneal bleeds, but we saw some bleeding at the site where you put the catheter in. And what we did see was 62% better rates of blood flow on arrival. And when you look at death, MI, stroke, heart failure, and stent thrombosis, we saw a 21% reduction in that composite endpoint

This is an important step forward to moving STEMI care into the home. Now what you’re going to see is a lot of devices — KardiaMobile by AliveCor — things to put on your chest and your fingers, implantable devices, so that we can move the diagnosis into the home.

You’re going to spit into a cup to tell if you’re troponin positive. I think you’re going to see more care moving earlier and earlier in the setting of study.

Harrington: You and I have talked about this with some biomarkers, like troponin that can be picked up through a wrist-worn device.

And, as you said, we can get an EKG in a very portable way through a variety of mechanisms. If we can get the EKG, get a biomarker, have a system that can evaluate all of those while you’re calling your doctor. Now we may even have drugs that can lower the risk and really continue to improve acute MI care. These are fabulous opportunities, and we’ve only just begun the process of figuring that piece out.

Gibson: But the best thing is not to have an MI in the first place. Get your LDL-C down to 19 mg/dL, get your weight down to what it was when you played college football like me. Heisman Trophy pose.

Harrington: I knew the Heisman pose was coming.

Gibson: It’s an exciting time. I feel like we’re back to how exciting it was in the 1990s with the obesity drugs, and everything going on.

Harrington: Mike, this has been, as always the highlight of my year on the podcast. We didn’t even get into areas like heart failure, electrophysiology, surgery, and procedures. We focused on the areas of excitement around atherosclerosis, the metabolic disease that remains the world’s largest cause of death and disability.

I’m glad that we’re able to have this conversation. Mike Gibson is my friend from Boston, interventional cardiologist, CEO of the not-for-profit CRO the Baim Institute, and professor of medicine at Harvard. Mike, thanks for joining us here on Medscape Cardiology | theheart.org.

And to our listeners, I hope that you’ve enjoyed the show. Give us your feedback. Let us know what you like. Give us a thumbs up and send us your recommendation for topics that you’d like us to cover. Mike, happy holidays.

Gibson: Happy holidays! Holiday love to everybody out there.

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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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: Cardiovascular Medicine 2025 Wrapped: The Big Picture - Medscape - Dec 30, 2025.