Association of Tirzepatide Use With Clinical Outcomes After Transcatheter Aortic Valve Replacement in Obese Patients: A Propensity-Matched Real-World Study

Interview by Laura Simson, MA

In this interview with JIC, Ibrahim Mortada, MD, of the University of Texas Medical Branch shares insights on his study, "Association of Tirzepatide Use With Clinical Outcomes After TAVR in Obese Patients: A Propensity-Matched Real-World Study," presented at the 2026 SCAI Scientific Sessions.

Your study shows improved outcomes with tirzepatide after TAVR for obese patients. Do you believe this is primarily related to weight loss effects, or are there other mechanisms driving this benefit, such as anti-inflammatory effects, direct cardiovascular or vascular effects, and how might future studies differentiate these contributions?

As you mentioned, tirzepatide works by many different mechanisms. We still don't know exactly how it has all these beneficial effects. It definitely has a component of anti-inflammatory endothelial function, weight loss, blood pressure control, glycemic control. So, it's really a combination of all of these mechanisms, and I don't think we can really single out just one mechanism and talk about it for these benefits.

In terms of isolating, I think we need to go back to the basic science, go back to the molecular level, try to look at the inflammatory markers, I would assume. Such studies can give us more insights on the exact mechanisms. But again, it's kind of hard to just point out one single mechanism; it's really more about the full action of tirzepatide on the different levels.

Your analysis shows a reduction in heart failure, hospitalizations, and MACE, but not in myocardial infarction (MI) or stroke. What do you think is driving the selective benefit?

It’s already established that tirzepatide has beneficial effects on heart failure. We have the SUMMIT trial, lots of trials actually were published in the New England Journal of Medicine highlighting this. We did not study MACE in particular as a composite, but we studied acute MI. We did not see any changes, any differences, I would say, between the 2 groups in terms of rates of MI.

But again, in terms of mechanism, as I said in my previous answer, it's really the full combination of beneficial effects.

There is a recent study that showed that semaglutide is associated with reduced risk of atrial fibrillation (AFib). Do you think that the positive outcomes you saw with tirzepatide are due to something unique about this drug in particular, or do you think other drugs, such as semaglutide, would have similar effects?

Well, actually, tirzepatide is a second generation of the GLP-1s—semaglutide is a first generation. So, I wouldn't be surprised if the same beneficial effects, are seen in tirzepatide as well. I know that currently there are even third and fourth generations of the GLP-1s that are being studied.

This is actually another topic of interest for me. I am also working on a different study looking at the rates of AFib and flutter after the use of tirzepatide.

Based on the data you were working with, can you describe how tirzepatide was being used in real-world practice among these patients? For example, how long were they on it before you came across them, were they adhering to the treatments, etc? And how may have those patterns influenced your findings? And then going forward, because this was a retrospective design, how would you design a prospective trial to counter these variables?

So, as you know, for this particular study, we used TriNetX, which is a federated research network of de-identified electronic medical record data. In particular, we used the Global Collaborative Network—it had data from around 170 healthcare organizations. So, unfortunately, one of the limitations of TriNetX is that it depends on the coding, whatever was coded in the chart, so we cannot really, know how long they've been on the drug, how compliant they have been. This is something that I have detailed in the limitations section of our manuscript.

Now, as you mentioned, of course, being a retrospective design, we cannot draw causality. So, it is very important to conduct prospective randomized trials to determine whether the initiation of these incretin-based therapies after TAVR can causally reduce heart failure events. I would also be interested to look at the optimal timing of the therapy initiation, how long they need to be on the drug, and even evaluate the long-term effects on the cardiac remodeling and the clinical outcomes.

For the second part of your questions, in terms of design, ideally, we would have 2 different cohorts of TAVR patients, and we would do randomization, whereby one cohort would be receiving the drug, and the other cohort would be on a control. And we would follow up on these 2 cohorts over time, we would regularly meet them, do some tests, evaluate how they're doing.

And I would say after 3 to 5 years we can then look at the hard outcomes in terms of mortality, hospitalization, acute MI, ischemic stroke, acute kidney injury, and then we can really draw causality and see whether tirzepatide is able, really, to improve outcomes in this patient population.

GLP-1s right now are a very interesting topic, and I think what matters the most right now is to conduct the prospective trials because this can definitely show us causality and it can have great impact on the health of the population.

Dr Mortada is a physician scientist at the Department of Cardiovascular Medicine in the University of Texas Medical Branch (UTMB), in Galveston, Texas, USA.