Editor’s 2025 Top 10: Prognostic Implications Over Time of Platelet FcɣRIIa Expression in Patients With Myocardial Infarction: A Secondary Analysis

Dr Deepak L. Bhatt, editor-in-chief of the Journal of Invasive Cardiology, catches up with Dr David Schneider about his Editor’s 2025 Top 10 article, “Prognostic Implications Over Time of Platelet FcɣRIIa Expression in Patients With Myocardial Infarction: A Secondary Analysis.”

Transcript: 

Dr Bhatt: Hello, I'm Dr. Deepak Bhatt, the Director of the Mount Sinai Fuster Heart Hospital in New York, and the Editor-in-Chief of the Journal of Invasive Cardiology, and we are featuring all the top articles from 2025. Today, I'm lucky to have with me a good friend and colleague, Dr. David Schneider, who was behind, I think, a very interesting paper looking at a new platelet function assay. So perhaps you could just tell us first about the assay, and then we can get into the specifics in the paper.

Dr Schneider: Great, thank you. It's really a pleasure to be here. This is a new type of test on platelets, so most available tests on platelets take a sample of blood, activate the platelets, and look at how likely they are to activate to assess platelet reactivity. Those tests have a variety of challenges associated with them. This test is different in that it quantifies a protein on the surface of platelets. The protein is FcɣRIIa, which is a mouthful, and so for the rest of our discussion, I'm going to refer to that as FCG. That molecule is known as a receptor, it's actually how platelets participate in the response to infection. It also is a key marker in heparin-induced thrombocytopenia and thrombosis.

Our interest in that marker is different. A recent observation—recent being over the last 10 years—is that this protein also serves to amplify platelet activation. So, conceptually, if you have more of this on the platelet surface, more copies of this molecule on the platelet surface, your platelets are more likely to activate. The simple concept here is that we're using flow cytometry, which allows us to count 10 000 platelets in a minute, and we're getting the average number of molecules of FcɣRIIa on the surface of platelets. Then we basically divide people into high and low risk based on the number of molecules they have on their surface. 

We had done some initial retrospective studies identifying a threshold at about 1750, and we've used that threshold in both of our studies, and it has held up in terms of demonstrating patients who are at high and low risk.

Dr Bhatt: Do you want to summarize what was found specifically in this paper in JIC?

Dr Schneider: I'd love to. This is a second analysis of our multicenter study; we now have 2 studies, a single-center study and a multicenter study, that have demonstrated that this marker can identify patients at higher and lower risk of subsequent events. We have looked at that traditional endpoint of 1 year and the hazard ratio of patients comparing high expression with low expression is about 2.1. We know that patients who have a myocardial infarction are at higher risk of recurrent admission and recurrent events, more so in the early time frame, and so in this analysis we looked at the time to event. We broke it into different increments focusing on the first month, the first quarter, the first half a year.

And to remind everybody what we saw in our study, similar to what is commonly seen, nearly 25% of patients have a recurrent event when they have it in the first month, 39% in the first quarter, and 60% in the first 6 months. What we found was the marker that had the general predictive capacity over the first year, with a hazard ratio of 2.1, was very predictive early on. During the first month, when we looked at the primary endpoint—heart attack, stroke, and death—the hazard ratio was 3.8, and over the first 6 months, the hazard ratio held true at 3.5. So, this is a marker that can particularly identify patients at high risk of recurrent events.

We think this is particularly meaningful because despite general recommendations for use of more powerful antiplatelet agents in patients with acute coronary syndrome, still approximately 60% of patients go home on clopidogrel. And particularly in the patients who had high platelet (p) FCG, we think that those patients could benefit from a more powerful therapy.

Dr Bhatt: So you think that this test could actually be used to guide therapy, to choose specific antiplatelet regimens and durations?

Dr Schneider: That's where we'd love to go. We think this could be a precision tool that we've been begging for in cardiology for some time. Right now, we haven't reached that threshold yet. We certainly can identify patients at greater risk, and I think we would say it could prod us to use guideline-directed therapy in people who have high pFCG.

But especially when combined with a bleeding risk score, we think now that we actually have tools that could allow us to identify specific treatment approaches for patients, whether you combine more powerful P2Y12 and then combine that with bleeding risk, decide on when you could de-escalate therapy. So we're excited about the future and are in the planning stages of multiple additional studies.

Dr Bhatt: Anything about FCG that is associated with bleeding risk per se?

Dr Schneider: That's an interesting finding. In our first study, we had so few bleeding events, we really couldn't make any statement. In this study, we definitely saw an association. When we completed a multivariate analysis, that association was weaker. To me, from a mechanistic perspective, it's a surprise to me that we saw patients having higher bleeding who had higher pFCG. I believe it's because of the association of higher pFCG with other factors, older age, renal disease, things that are definitely associated with bleeding.

Dr Bhatt: Well, that's terrific. What about next steps?

Dr Schneider: For us, I think the next step is to get a multicenter study that allows us to test guiding treatment with this marker, and I think that will get us to the point that we have envisioned now for a number of years.

Dr Bhatt: Terrific. Well, congratulations on all this research and all these successes. Any final thoughts for the audience?

Dr Schneider: We're excited to be able to help cardiologists make better decisions. This is a wonderful opportunity that we feel we're able to give to cardiologists.

Dr Bhatt: Great, well, thank you for continuing to advance the science in publishing in JIC.

Dr Schneider: Thank you.

The transcript has been lightly edited for clarity.