Threshold for Transfusion in ACS: Still Room for Discretion

Cardiologists Michelle O’Donoghue and Sunil Rao discuss more details from the MINT trial on a liberal vs conservative approach to blood transfusion in patients with anemia and acute coronary syndrome.
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Michelle L. O'Donoghue, MD, MPH: Hi. This is Dr Michelle O'Donoghue, reporting for Medscape. Joining me today is Sunil Rao. He is a professor of medicine at NYU Grossman, as well as director of interventional cardiology at NYU Langone. Welcome, Sunil. Thanks for joining me today.
Sunil V. Rao, MD: Thanks for having me.
O'Donoghue: One of the more interesting trials that was both published last year in The New England Journal of Medicine and a subgroup analysis is being presented at the American College of Cardiology (ACC) Scientific Session 2024 is from the MINT trial.
Before we get into this new substudy from MINT, let's take a step back and think about strategy trials in general, in terms of thinking about transfusing people to a higher hemoglobin level vs just leaving people with anemia. We've known for years that lower hemoglobin is associated with worse outcomes, but the question mark has always been, do you transfuse people and does that translate into better outcomes?
Hemoglobin Threshold
Rao: I think you framed the question perfectly. There have been historical data that suggest that we should maintain the hemoglobin at 10 g/dL in patients who have coronary artery disease. There are observational data from patients who, for example, refused transfusions because of religious beliefs, suggesting that even in patients undergoing bypass surgery, you can push their hemoglobin down to 6 g/dL without any sequelae.
The question has always been not whether we should give a transfusion, but how much we should give and what is that transfusion trigger? On the basis of observational data, the two triggers that have emerged are a hemoglobin level of 8 vs 10 g/dL. There have been plenty of randomized trials, as you've noted, in other settings, such as critical care, infectious disease, and even gastrointestinal bleeding, suggesting that a so-called liberal or aggressive transfusion strategy is really no better than letting patients ride out a lower hemoglobin level.
Interestingly, most of those studies - in fact, probably all of them - have excluded patients with an acute coronary syndrome. In the acute coronary syndrome setting, one can imagine a rationale for pushing the hemoglobin higher because hemoglobin is part of the oxygen delivery equation. These patients have already manifested some kind of hypoxic insult with an acute myocardial infarction (MI), so potentially maintaining a higher hemoglobin level should be beneficial.
The flip side, of course, is that transfusion of packed red cells that are stored is not the same as the red cells that are in our bodies. They are depleted of nitric oxide and 2,3-diphosphoglyceric acid. They may not in fact deliver oxygen very well. Some data suggest that there may be some platelet activation as well, so there's potential for harm.
That is really what set up the MINT trial, which is a National Heart, Lung, and Blood Institute-funded study of 3500 patients with acute coronary syndrome. Acute MI and all kinds of MI were allowed in this trial: type 1 as well as type 2. They were randomized to maintain a hemoglobin of 8 g/dL, in the so-called conservative transfusion strategy, or 10 g/dL, in the so-called liberal transfusion strategy. It’s interesting that we use those terms in today's political environment, but those are exactly the terms that we use.
O'Donoghue: What did the primary results of MINT show?
Rao: It's a fascinating study. It's the largest randomized trial in this particular population. The trial just barely missed conventional statistical significance. We had to conclude that really there was no significant difference in terms of the two strategies, but all the point estimates lined up on the side of liberal transfusion, which was maintaining a hemoglobin level of 10 g/dL.
Cardiac death - the caveat being it was not adjudicated in the trial - actually favored the liberal transfusion strategy. I think from a pragmatic bedside standpoint, it does seem that a more liberal transfusion strategy probably is beneficial in patients with acute MI.
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