Gray Areas and Controversies in the 2025 ACS Guidelines, With Michelle O’Donoghue, MD, MPH

Although the 2025 guidelines for the management of acute coronary syndromes (ACS) are exhaustive and relatively all-inclusive, recent research has highlighted gray areas, controversies, and potential points of confusion for clinicians.

At the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana, the editorial team at HCPLive spoke with Michelle O’Donoghue, MD, MPH, the McGillycuddy-Logue Endowed Chair in Cardiology, associate professor at Harvard Medical School, and member of the original guideline authors, to discuss the presentations she chaired regarding the ACS guidelines.

“The body of knowledge that we have to support our recommendations continues to evolve at a pretty dizzying pace, so it’s almost hard for guideline writers to keep up,” O’Donoghue told HCPLive in an exclusive interview. “Part of what we’d like to discuss during this session is the subsequent evidence that has come to light post-completion of the guidelines and how that might shape our thinking.”

The guidelines were initially drafted following a comprehensive literature search, which was conducted from July 2023 to April 2024. The process included clinical studies, systematic reviews, meta-analyses, and other evidence involving human participants. However, O’Donoghue notes that the constant and rapid evolution of research in both ACS and more broadly in cardiology means that any guidelines will be incomplete after publication.1

O’Donoghue also indicated several gray areas within the guidelines in terms of treatment, particularly regarding beta blockers. These decrease myocardial oxygen demand via a reduction in the heart rate, blood pressure, and myocardial contractility. Although beta blockers have a well-established clinical benefit in patients with left ventricular ejection fraction (LVEF) <40% and stabilized heart failure, no adequately powered trials have examined the benefit of beta blockers during hospitalization for patients with non-ST-segment elevation ACS (NSTE-ACS).1

“Beta blocker therapy is one of the areas where there continues to be additional clinical trials that have been released since the finalization of the 2025 document,” O’Donoghue said. “I think that’s going to be an interesting discussion – how do we start all patients with an ACS on beta blockers at the beginning, and do we continue it post-discharge? Is it only going to be a select group of patients that we continue beta blocker therapy? Is there any risk from beta blocker discontinuation?”

Ultimately, O’Donoghue suggests that documents such as the ACS guidelines inevitably need to be transformed into a “living document” – in other words, a version that is open to regular updates following the completion of new trials or the release of new suggestions.

“There is a plan to make it more of a living document, and some of that might be in the form of more annual – or at least regular – updates rather than completely redrafting the whole document,” O’Donoghue said. “We need more focused updates, since we certainly went too long with a 10-year gap between the last version of the ACS guidelines and this new release.”

Editors’ Note: O’Donoghue reports disclosures with Amgen, Novartis, Janssen, AstraZeneca, GlaxoSmithKline, Intarcia, and others.

References

1. Rao SV, O’Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes: A report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation. 2025;151(13). doi:10.1161/cir.0000000000001309