High-Impact Trials at ACC.25 Signal Shift in Chronic Disease Treatment

At the American College of Cardiology Annual Scientific Session (ACC.25), experts shared groundbreaking research poised to reshape cardiovascular care—particularly for women and patients with complex cardiometabolic conditions. From promising data on glucagon-like peptide-1 (GLP-1) and sodium-glucose cotransporter 2 (SGLT2) inhibitors to overdue attention on conditions like peripheral artery disease (PAD) and ischemia with no obstructive coronary arteries (INOCA), the conference emphasized a shift toward more personalized, evidence-based treatment strategies.

According to experts who attended the meeting to present research, highlights included the SOUL (NCT03914326) clinical trial confirming the cardiovascular benefits of oral semaglutide; the STRIDE (NCT04560998), WARRIOR (NCT03417388), and DapaTAVI (NCT 04696185) trials suggesting progress in treating patients with PAD; and renewed calls for better care models for women. Across sessions, experts praised the quality of randomized controlled trials and the momentum building toward integrated, preventive care.

This transcript has been lightly edited; captions were auto-generated.

From your perspective, what was the most exciting topic focused on this year at ACC.25?

Christian T. Ruff, MD, MPH, director of General Cardiology at Brigham and Women’s Hospital; associate professor at Harvard Medical School; senior investigator, TIMI Study Group:

From the first day of the conference, I think we had great data on a better understanding of how to optimally treat women with cardiovascular disease. And I was encouraged that we're moving the needle and more women are being treated, potentially with guideline therapy, but obviously, we have a lot more work to do to understand how to further optimize therapy in women who have different risks for atherosclerotic cardiovascular disease. I'm excited that there's been a tremendous amount of research being done, and I think it just enables us to decide what the next round of studies are to better inform practice.

At the ACC and at all the recent conferences, I think what I've been most amazed and excited about is just the incredible data that's coming out with the incretins, particularly the GLP-1 inhibitors, and obviously, just this building cascade, first in diabetes and weight loss, and then heart failure, coronary disease, and now data presented in peripheral arterial disease, to have a drug that just dramatically changes someone's cardiometabolic profile, atherosclerosis, heart failure, weight loss, kidney disease.

It's just a remarkable therapy that improves patients' lives; they live longer; they're at less risk of diabetes, heart disease, heart failure. It's just incredibly exciting. I think these drugs, with the future trials, have an ability to revolutionize the burden of chronic disease in patients. It's an exciting time, and I think when we look back 10 years from now, it'll just be remarkable.

John B. Buse, MD, PhD, director of the Diabetes Care Center; professor at the University of North Carolina School of Medicine:

There have been a number of disclosures from this meeting that I do think are going to change guidelines in the near future. With the SOUL trial, we now have proof that oral semaglutide is associated with cardiovascular benefit; that's going to be added to the list of drugs associated with cardiovascular benefit.

I saw a great abstract in the same session on the use of an SGLT2 inhibitor in the setting of transaortic valve replacement, reducing important outcomes in a very meaningful way, and the discussants pointed out that even though there have been indications for using these SGLT2 inhibitors to prevent heart failure outcomes and death in patients with heart failure, they aren't generally applied in the setting of post–aortic valve replacement, and so that that's another real opportunity for improving the health of the segment of the population.

Then, both in one of the secondary outcomes of our study in SOUL and in another study called STRIDE, which examines semaglutide in patients with peripheral arterial disease, both of our studies suggest substantive benefits in a really difficult population to treat, namely patients with diabetes and peripheral arterial disease. So that data isn't solid enough that it's going to change guidelines tomorrow, but it's certainly going to enhance the conversation about what we can do for people with peripheral arterial disease in the setting of diabetes, and it does seem that SGLT2 inhibitors are perhaps part of the solution there.

Marc P. Bonaca, MD, MPH, executive director of CPC Clinical Research; director of Vascular Research; professor in the Division of Cardiology at the University of Colorado School of Medicine:

This has been a fantastic meeting; within the session, there was the WARRIOR trial. I think that was a fantastic trial looking at all women with INOCA, which is a really hard thing to treat, and I think the recognition that they had high event rates of readmission to the hospital, knowing they didn't have obstructive coronary disease, it's a little wake-up call that we need more therapy.

The other trial I find particularly exciting is SOUL. SOUL is a large outcomes trial with oral semaglutide, and the oral drug worked just as well as the injectables, and there was a significant reduction in major adverse limb events, which I think really complements the STRIDE trial. There are also some exciting trials for antithrombotics and other things, but I think PAD gets a special place in this meeting, and that's pretty rare. We haven't had a newly approved drug for functional symptoms in PAD for 25 years, and so to me, that's the take-home.

Marc Humbert, MD, PhD, dean of the University Paris-Saclay and Inserm medical school in France; professor of respiratory medicine:

I am a respiratory doctor, and I'm very impressed by the high quality of the randomized controlled trials presented at ACC. I could see very, very important data, for example, on anticoagulation in people with cancer-associated thrombosis. And I was very impressed by the high quality, high engagement of this community for better demonstration of significant outcomes with new therapies or new therapeutic approaches.

Jawad Haider Butt, MD, PhD, of Glasgow Cardiovascular Research Center, University of Glasgow:

There were many interesting topics, and the one that I find the most interesting is the DapaTAVI trial, which was a trial that included patients who were undergoing a TAVI [transcatheter aortic valve implantation] procedure, and they were randomized to dapagliflozin or placebo. And that, I think, is a very important trial, and it will definitely, to some extent, change clinical practice.

​​Siddharth M. Patel, MD, MPH, cardiologist at Brigham and Women's Hospital; investigator at TIMI Study Group:

There was so much great science ranging from the use of mechanical circulatory support in patients with cardiogenic shock to the newer GLP-1 RA [receptor agonist] therapies across the spectrum of really cardiovascular, kidney, and metabolic disease. And so I think it's an exciting time to be in cardiology, and lots of new therapies on the horizon to improve patient outcomes.