(Updated) The latest research undermines the role of these long-standing agents, suggesting their use is reminiscent of a bygone era.
ATLANTA, GA—New study evaluating long-term use of beta-blockers in patients with acute myocardial infarction and preserved ejection fraction shows these drugs reduce risk in the era of modern post-myocardial infarction care Death or recurrent myocardial infarction again suggested that there was no use for it.
Study leader Troels Yndigegn, MD, Lund University/Skein University Hospital, Sweden, today presented results from the registry-nested REDUCE-AMI randomized trial along with data at the 2024 Scientific Sessions of the American College of Cardiology (ACC). did. The results showed that the Kaplan-Meier curves for the primary endpoint of death or recurrence of myocardial infarction were “mixed and virtually overlapping” between his two treatment groups.
Senior researcher Thomas Jarnberg, MD, Danderyd Hospital/Karolinska Institutet, Stockholm, Sweden, says it may be wise to wait until guidelines catch up with the latest evidence, but widespread recommendations for beta-blockers may be lowered. He said that there is a high possibility that After acute myocardial infarction, he feels it is okay to avoid administering beta-blockers to post-myocardial infarction patients as long as LVEF is intact.
The REDUCE-AMI study is not the first study to challenge the use of beta-blockers in modern post-MI patients, and several observational studies have also been included. arrival And clarification—suggesting that there is no benefit to beta-blockers given in addition to modern medical therapy. Back in 2014, researchers Meta-analysis of over 60 trials A study of 100,000 patients found that beta-blockers prescribed after acute myocardial infarction did not reduce the risk of all-cause mortality during the reperfusion period.
Sripal Bangalore, MD (NYU Langone Health, New York, NY), who led the meta-analysis, is pleased that randomized data finally exist to address this clinical question.
“If you think about it, there are a lot of treatments that have been passed down to us,” he told TCTMD. With each advancement, this new treatment is added to those that have worked in the past, resulting in patients taking multiple medications after an MI. However, if you look closely at the data, [older] In this day and age, the trial will be completed successfully,” Bangalore said.
One of the biggest challenges after a heart attack is taking hundreds of millions of medications. wayne batchelor
Wayne Batchelor, MD, chair of the ACC Intervention Council (Inova Heart and Vascular Institute in Fairfax, Virginia), agreed that REDUCE-AMI allows physicians to take a “slightly reductionist” approach to treatment. . “One of the biggest challenges after a heart attack is taking hundreds of millions of medications,” Batchelor says. “We can say with some confidence that if your LV ejection fraction is maintained above 50% and you have no other reason to take a beta-blocker, you probably don’t need to take a beta-blocker. It has become.” That is. ”
The new research New England Medical Journal In line with the ACC presentation.
Randomized trials nested in registries
Jernberg told TCMDD that there is “very strong data” showing that beta-blockers reduce the risk of death after massive myocardial infarction in patients with left ventricular dysfunction, but those trials He explained that it was carried out in the 70s and 80s, predating modern times. We conduct research on modern medical management using PCI, high-sensitivity troponin testing, statins, antithrombotic therapy, and ACE inhibitors/ARBs.
inside european guidelinesBeta-blockers are a class Ia recommendation for ACS patients with LVEF ≤ 40%, while 2a approval has been granted for routine use in all ACS patients. U.S. guidelines recommend that doctors start beta blockers if: ACS patients with STEMI (Class I recommendation, level of evidence B) and NSTE-ACS patients with and without systolic dysfunction (class I, level of evidence C and class IIa, level of evidence C, respectively).
To study the effectiveness of beta-blocker therapy in a more modern era, REDUCE-AMI researchers conducted a parallel-group, open-label study in 45 hospitals in Sweden, Estonia, and New Zealand using registry data. A test was conducted. More than 95% of patients were from Sweden, data on MI were collected from the SWEDEHEART registry and mortality through linked national databases. In Estonia and New Zealand, baseline data were collected using electronic case report forms similar to those used in SWEDEHEART and through hospital health records for follow-up.
Acute myocardial infarction patients (median age 65 years, 22.5% female) with obstructive CAD and preserved LVEF (>50%) who underwent coronary angiography were randomized to treatment with beta-blockers or no treatment. Ta. Between 2017 and 2023, 2,508 people were treated with metoprolol succinate (62.2%) up to a target dose of 100 mg or bisoprolol (37.8%) up to a target dose of 5.0 mg, and 2,512 people were not treated with a beta-blocker. Over a third (35%) presented with her STEMI and over 95% underwent PCI. At discharge, 97% were treated with aspirin, approximately 96% with P2Y12 receptor antagonists, and almost all patients received statins.
Of more than 5,000 patients with either STEMI or NSTEMI who underwent coronary angiography during hospitalization, 7.9% of patients were treated with beta-blockers and 8.3% of patients did not receive beta-blockers. All-cause death or myocardial infarction occurred. Beta-blocker administration with median follow-up of 3.5 years (HR 0.96; 95% CI 0.79-1.16). Furthermore, there was no benefit in any of the secondary endpoints or in any prespecified subgroups.
Batchelor told TCTMD that REDUCE-AMI primarily addresses historical issues, noting that before the advent of coronary revascularization and other treatments, LVEF was typically impaired after a myocardial infarction. did.
“We don’t see very low ejection fractions as often as we used to,” he told TCTMD. “Those patients still exist, and unfortunately many of them are in cardiogenic shock, but all the patients with preserved heart function were treated with beta-blockers. This is because the guidelines supported its worldwide use after myocardial infarction.” This study allowed us to refine it further. ”
Regarding the beta-blockers used in the study, Batchelor said these were the most effective drugs, but noted that the researchers only had data on one year of use, and noted that the drugs He said it was unclear how strongly the push was being made. Additionally, safety endpoints such as bradycardia and other arrhythmias were similar between treatment groups, meaning the drug may not have been used at maximum doses.
“If they’re not maximally enhanced, they might lose a little bit of their therapeutic value there,” he said.
Bangalore, Batchelor et al. noted that the incidence of the primary endpoint (2.4% and 2.5% per year in the beta-blocker and non-beta-blocker groups, respectively) was much lower than the researchers expected. Patients with near-normal LVEF, who underwent revascularization and received first-class care.
“This is symbolic of how well we treat our patients,” Batchelor said. “These patients received excellent interventional therapy. They were all on statins, they were all on aspirin, and they were all on P2Y12 inhibitors. So in all of these areas of intervention, we’re detecting signals from beta blockers. It is simply impossible.”
“This shows how far we have come in treating MI,” Bangalore said.
Maybe it’s not over yet?
P. Gabriel Stegg, MD (Bichat Hospital, Paris Hospital Auxiliary, France), stressing that the results apply only to the study population and not to high-risk patients, such as those with LVEF < 50% or those who did not undergo revascularization.
Professor Stegg noted that double-blind randomized trials are preferable to open-label designs, noting that the crossover after one year is not negligible: 18% discontinued in the first year, but 14% of those randomized to not taking beta blockers started treatment. He also reminded doctors that “absence of evidence is not evidence of absence,” adding that the confidence interval included a 21% chance of reducing risk with beta-blockers.
“Given the difficulty of clearly demonstrating no benefit to beta-blocker treatment and the limitations of a single open-label trial with somewhat underpowered trial results, it is important to note that beta-blockers are not definitively recommended by secondary prevention teams. It may be premature to rule out routine beta-blocker therapy after myocardial infarction while awaiting the results of multiple upcoming trials that will re-evaluate the role of beta-blockers in modern therapy. It may be wise to put it in “damage reserve”. ”
More randomized studies of beta-blockers after MI should help further clarify the picture. dumb block, Betami, rebootand AβYSS All expected in 2024 as well as wise decision And then comes ABBREVIATE, Steg writes.
Five or 10 years ago, beta-blockers were considered the basis of evidence, the cornerstone of MI treatment. Sripal Bangalore
To TCTMD, Bangalore acknowledged that REDUCE-AMI has limitations given that it is a registry-based randomized trial, but nevertheless, the practice of reflexively prescribing beta-blockers after acute myocardial infarction He admitted that he needed to change his mind about this.
“In the case of acute myocardial infarction, at least in our clinical practice, we would start the patient on other treatments and prescribe a beta-blocker at the end, perhaps before discharge,” he said. “This trial comes at a time when people are becoming more tolerant of: [stopping beta-blockers]. Five or 10 years ago, beta-blockers were considered the basis of evidence, the cornerstone of MI treatment. However, we believe now is the right time and are hopeful that things will change. ”
“I think this will change practice,” Batchelor agreed. “I think there will be a kind of peeling back of this inevitable response of prescribing beta-blockers to everyone who has a heart attack.”
