Reference: N Engl J Med. 2025 Aug 30 early online
Practice Point: Long-term beta-blockers after myocardial infarction (MI) seem to slightly reduce future MIs but not death in patients with ≥ 40% ejection fraction (EF).
EBM Pearl: The abbreviated verbiage of abstracts lends itself to misinterpretation. (In other words, sometimes you need to read the fine print.)
For decades, beta-blockers have been a mainstay of post-MI therapy. They literally calm the heart, reducing its workload and letting the body repair itself. For most people who experience an MI, beta-blockers become a lifelong prescription; necessary either to reduce anginal symptoms or mitigate the loss of contractile function. For a small subset of patients, however, the benefits of ongoing beta-blocker therapy aren’t as obvious because they may have normal or only mildly depressed contractility (an EF of 40% or higher), minimal symptoms, and no additional condition in which beta-blockers are the ideal therapy.
Last month, the New England Journal of Medicine (NEJM) published an article from a Scandinavian group that enrolled 5,574 people with an EF of 40% or higher soon after an MI and randomized them to either continue long-term beta-blockade after their initial recovery period or to have beta-blockers gradually tapered off over time in follow-up visits. Half the patients had an ST segment elevation, and more than 90% received a percutaneous intervention. Only 20% of patients were female, a potential confounder of the data. Patients with either an EF < 40% or other indications for beta-blockers, such as ongoing angina, were excluded. The majority of patients in the beta-blocker group ended up taking about 50 mg/day of long-acting metoprolol, and about 10% of patients in both groups crossed over (either gradually tapering off beta-blockers or starting them up when they weren’t originally supposed to be on them).
Patients were managed by their own physicians and followed for an average of 3.5 years. The primary endpoint was a composite of all-cause death and major adverse cardiac events (MACE). The secondary endpoints included death and individual MACE events such as stroke or heart failure episodes. The primary endpoint showed benefit: 14.2% of people enrolled in the beta-blocker arm either passed away or experienced MACE vs. 16.3% of those in the non-beta-blocker group, with a hazard ratio of 0.85 (95% CI 0.75-0.98). Most of that benefit was driven by a reduced incidence of new MIs: 5% in those on beta-blockers vs. 6.7%, a statistically significant difference. On the other hand, the difference in all-cause mortality (4.2% vs. 4.4%) was not statistically significant. In other words, beta-blocker therapy did not reduce deaths.
That last detail is the source of a quibble we have with the abstract of this paper. The abstract states that in this study for this population, “beta-blocker therapy led to a lower risk of death or major adverse cardiac events than no beta-blocker therapy.” If you read that sentence on its own, wouldn’t you think that beta-blockers reduced both death and MACE events? That isn’t the case. They reduced a composite of MACE events and death, but they didn’t reduce death. It could be just a simple matter of English being the second (or third or fourth) language for the notoriously polyglot Scandinavians, but our friends at NEJM who edited the paper presumably don’t share that excuse. A more precise sentence would be: “beta-blocker therapy led to a lower risk of a composite of death and ….” This may seem like nit-picking, but it’s not: skimmers of the medical literature and most uncurated AI engines would almost certainly take away the message that beta-blockers reduce death in this population. (Note: Dyna AI only pulls information from DynaMedex, which is curated by human experts.) Beta-blockers might prevent death, but you can’t conclude that based on this research.
For more information, see the topic Management of Acute Coronary Syndromes in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Gayle Sulik, PhD, Senior Medical Editor and Team Lead for Palliative Care at DynaMed; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed; Matthew Lavoie, BA, Senior Medical Copyeditor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.