What Now for Beta-Blockers Post-MI? Reconciling REDUCE-AMI and ABYSS

Описание: Do the delayed safety concerns seen with beta-blocker discontinuation conflict with or complement REDUCE-AMI showing no benefit of early drug initiation? Drs O'Donoghue and Montalescot discuss.
https://www.staging.medscape.com/view...

-TRANSCRIPT-
Michelle L. O'Donoghue, MD: Hi. I'm Michelle O'Donoghue reporting for Med scape. I'm at the European Society of Cardiology (ESC) Congress in London, and I'm joined by Dr Gilles Montalescot. He's a professor of cardiology at Sorbonne University. One of the more interesting, and perhaps surprising to some, results that were presented at this congress were the results of the ABYSS trial. This was a trial of beta-blocker discontinuation.

Before we get into the results of ABYSS, let's take a step back and set the stage for the beta-blocker research, because for many years, we hadn't seen much in this space. What do we know about the benefit of beta-blockers after myocardial infarction (MI) or for patients with stable coronary disease?

Beta-Blockers: The Backstory
Gilles Montalescot, MD, PhD: It's a very good question. Clearly, the studies that we have with beta-blockers are old studies — old randomized studies done even before the era of mechanical reperfusion. What we have seen more recently is big registries suggesting that in this kind of patient, very much a stable patient, you may question the role of beta-blockers for secondary prevention.
It's very tempting for the physicians in everyday practice to say, "You're doing, well, nothing has happened in 1-3 years since your MI, we can probably remove the beta-blocker and have a better quality of life." But we needed a randomized study to be sure that safety was also okay.

O'Donoghue: You're right. We had a lot of observational studies that supported the idea that stopping beta-blockers, especially years after having an MI, may be a safe strategy. And a lot of patients are happy to be rid of some of their medications. Now in 2024, it's been a big year for beta-blocker research. Earlier this year, what did we learn from the REDUCE-AMI trial?

Montalescot: REDUCE-AMI looked at the introduction of beta-blockers in patients hospitalized for an acute MI when there is no left ventricular (LV) dysfunction, no heart failure — let's say a simple MI, the patient is doing well. Their hypothesis was that beta-blockers might have no benefit, and this is what they found.

Our study is very different. We are looking at patients who had an MI 3 years earlier (on average) and who were still on beta-blockers. We randomized 3700 patients to either beta-blocker removal or continuation. We wanted to show that there was no harm and that we may also improve the quality of life, which is a big issue for the patients.

The ABYSS Results
O'Donoghue: Ultimately, what did the results of ABYSS show?

Montalescot: T he exact opposite of our initial hypothesis. We were unable to show noninferiority of interruption of beta-blocker vs continuation. We had an excess of events, numerically speaking, when we stopped the beta-blocker. That was a surprise. That was a safety signal.

Of course, the study was open label. We had all sorts of beta-blockers with different doses, so as you can imagine, it was very difficult to have a blinded trial. That's a limitation of the study, but at the end of the day, when you look at death, MI, stroke, and rehospitalization for any cardiovascular reason, the curves tend to diverge after 3 years. We see an excess of hospitalizations, for coronary reasons mostly, when we stopped beta-blockers.

O'Donoghue: You make an important point there, that it was a broad composite outcome. For death, MI, and stroke, there was not much of a signal toward any increase in those outcomes with beta-blocker discontinuation. But there was a profound effect on hospitalization for cardiovascular reasons. So do we think that it's anginal symptoms driving those hospitalizations?

Montalescot: That was clearly angina, and it led to more coronary angiograms, more percutaneous coronary interventions. We also observed poor control of blood pressureand heart rate. It was a 4–mm Hg difference in diastolic blood pressure and a 10-beats/min difference for heart rate with beta-blocker discontinuation. We know that blood pressure and heart rate are prognostic markers in these patients, I'm not saying that it clearly explains what happened. The study stopped at 3, 4, or 5 years of follow-up for some patients, but the curves diverge. What would we have seen if we had 6 or 7 years of follow-up? I don't know, but we probably would see a significant difference.

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