Beta-blockers Not Helpful After MI in Patients With Preserved EF

Beta-blockers provide no clinical benefit to post-MI patients with preserved left ventricular ejection fraction, according to a potentially paradigm-changing meta-analysis.

The findings, published online this week in the New England Journal of Medicine and presented at the 2025 American Heart Association Scientific Sessions, give the “final word” in a field laden with an excess of often conflicting data, senior author Borja Ibáñez, MD, PhD (Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain), told TCTMD.

Among almost 18,000 patients with an LVEF ≥ 50% enrolled in the REBOOT, BETAMI-DANBLOCK, REDUCE-AMI, and CAPITAL-RCT trials, beta-blockers did not reduce the primary composite endpoint of all-cause death, MI, or heart failure over a median follow-up period of 3.6 years compared with a treatment strategy of no beta-blockers (8.1% vs 8.3%; HR 0.97; 95% CI 0.87-1.07).

Current US guidelines recommend starting beta-blockers within 24 hours following ACS to reduce the risk of ventricular arrythmias and reinfarction (class 1, level of evidence A), and European guidelines advise routine beta-blockers use for all ACS patients regardless of LVEF (class IIa, level of evidence B). But decades-old data have informed these recommendations, often from studies conducted before the advent of PCI with DES and contemporary guideline-directed medical therapy, among other advancements.

“This is one of these few cases that [it] is clearly the final nail in the coffin,” Ibáñez said, citing the “robust” individual patient-level data studied here. He expects the next iterations of ACS guidelines to reflect the new data.

“This is not the first time that this has happened in cardiology,” he continued, referring to interventions or therapies proven beneficial in the past and long in use but that are no longer helpful with improvements in both baseline therapies and other aspects of care.  

Sripal Bangalore, MD (NYU Langone Health, New York, NY), who has previously challenged the necessity of beta-blockers in this population, agreed. “This is why in our field this is so very important,” he said. “We had said over a decade ago that the type of MIs we are treating, the therapies we have [are] not the same as it was in the past. This would again reinforce the notion that we need to constantly keep reevaluating some of the therapies that we have been pushing for based on trials, which are done many, many, many decades ago.”

The new data are “finally giving us a definitive answer,” Bangalore continued. “The answer is very clear that if you have MI and preserved EF, there is no benefit of using a beta-blocker.”

No Difference in Outcomes

For the analysis, researchers led by Anna Meta Dyrvig Kristensen, MD (Copenhagen University Hospital, Denmark), looked at individual-level data from 17,801 patients enrolled in the five trials (median age 62 years; 20.7% female) randomized to beta-blockers (49.6%) or no beta-blockers (50.4%). Previous MI was recorded in 8.1% of the population and atrial fibrillation in 2%. Almost half (45.7%) had STEMI, and 94.4% underwent PCI.

The incidence rate of the primary endpoint overall was 2.41 per 100 person-years. There was no difference in risk between the two treatment groups after excluding REDUCE-AMI (HR 0.97; 95% CI 0.86-1.10), a trial that used nonadjudicated endpoints.

The answer is very clear that if you have MI and preserved EF, there is no benefit of using a beta-blocker. Sripal Bangalore

There were no differences observed between the two arms for any individual endpoint: neither all-cause death (HR 1.04; 95% CI 0.89-1.21), MI (HR 0.89; 95% CI 0.77-1.03), nor heart failure (HR 0.87; 95% CI 0.64-1.19). These results were maintained in all subgroup and sensitivity analyses.

Rates of ischemic stroke and advanced atrioventricular block were comparable as well.

With each of the individual trials being published in recent years painting a picture of beta-blockers that contradicted routine practice, one—BETAMI-DANBLOCK—stood out with a signal that these drugs might benefit patients with an LVEF of between 40-49%. “This is why we thought that it was extremely relevant to pull together all these trials and perform an individual patient data meta-analysis to have the final answer,” Ibáñez said, adding that the cutoff should be set at an LVEF of at least 50%.

‘Immediate Uptake Worldwide’

“This is going have an immediate uptake worldwide—not only for patients who are discharged from now on after an MI, who will not be prescribed beta-blockers—but it also will be relevant for patients who are already on beta-blockers [for] several years before,” he said. “I think that most of them [will] be also withdrawn for beta-blockers.”

There will also be implications for patients on beta-blockers for hypertension, according to Ibáñez, who cited current hypertension guidelines that recommend beta-blockers for patients with previous MI. “Maybe for these patients getting beta-blockers for hypertension, they will be switched to ACE inhibitors/ARBs, which we know [have] much stronger benefits,” he suggested.

He stressed, however, the importance of patients not going off beta-blockers without first consulting their doctor. “We know that beta-blockers are still beneficial for other populations, for example, patients after MI with a low ejection fraction [or] with atrial fibrillation, which you would want to have heart rate control,” Ibáñez said.

The message should not be ‘stop beta-blockers after MI,’ but rather ‘consider withdrawal only when the residual ischemic and arrhythmic risk is truly minimal.’ Johanne Silvain

Johanne Silvain, MD (Sorbonne Université, Paris, France), who led the ABYSS trial showing a potential safety risk associated with stopping beta-blockers in post-MI patients, doubled down on this last point.

“I fear that the overall message might be somewhat oversimplified, as there remains a substantial subset of patients who will still clearly benefit from beta-blocker therapy after MI,” he told TCTMD in an email. “My concern is that the current narrative risks portraying beta-blocker withdrawal as broadly safe, while in fact this is true only for a small subset of carefully selected, low-risk patients. Many others—those with larger infarcts, mild LV dysfunction, incomplete revascularization, or concomitant hypertension—continue to derive clear benefit. In these subgroups, discontinuation could be harmful.”

It is essential to interpret the data with nuance, Silvain continued. “The message should not be ‘stop beta-blockers after MI,’ but rather ‘consider withdrawal only when the residual ischemic and arrhythmic risk is truly minimal,’” he said.