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Beta-Blockers Fail to Deliver Secondary Prevention Benefit in Key MI Patients

— Standard medications losing appeal amid more modern heart attack treatments

Ƶ MedicalToday

ATLANTA -- Beta-blockers had no additive benefit over contemporary therapies for people with acute myocardial infarction (MI) maintaining a preserved left ventricular ejection fraction (LVEF), the REDUCE-AMI randomized trial showed.

With beta-blockers initiated in the days following an MI, patients showed no significant change in combined all-cause death or new MI rates over a median 3.5 years of follow-up (7.9% with beta-blockers vs 8.3% without, HR 0.96, 95% CI 0.79-1.16), Troels Yndigegn, MD, of Lund University in Sweden, reported here at the American College of Cardiology (ACC) annual meeting.

Additionally, no significant between-group differences were detected for mortality alone (3.9% vs 4.1%), cardiovascular death alone (1.5% vs 1.3%), or MI alone (4.5% vs 4.7%). Moreover, the researchers couldn't find evidence that beta-blockers helped with dyspnea and angina symptoms in either the short term (6-10 weeks) or longer term (11-13 months).

The full manuscript from the Swedish registry-based REDUCE-AMI trial was published in the (NEJM).

Beta-blockers were not associated with any excess safety events, according to Yndigegn and colleagues.

Even so, their trial represents part of the turning tide against beta-blockers as a routine long-term treatment after MI, a concept that goes back to the days of the pre-reperfusion era. Nowadays, as was in the case in the study, MI patients are nearly all treated with percutaneous coronary intervention (PCI) in the hospital and discharged with aspirin, P2Y12 inhibitors, statins, and other modern medications.

have already stopped recommending beta-blockers past 1 year after an MI unless there is low LVEF, hypertension, arrhythmia, or another indication for this therapy.

"We certainly don't want practitioners thinking we don't need beta-blockers anymore after heart attack. This is absolutely not the case," commented Kim Eagle, MD, of University of Michigan in Ann Arbor. Only in patients without an injured left ventricle or a tendency toward arrhythmia, would it be "safe to say their relative benefit is less than it used to be."

"For patients with MI and preserved ejection fraction, where there's some question of whether we really want to slow heart rate or lower blood pressure, it's fair to say this [trial] may be practice-changing," he said in an interview.

Even for these patients, however, P. Gabriel Steg, MD, of Université Paris-Cité and Assistance Publique-Hôpitaux de Paris, emphasized that "an actual benefit with beta blockers cannot be ruled out" based on REDUCE-AMI alone.

accompanying the NEJM study, he voiced concerns about relatively low doses of beta-blockers given and the "not negligible" crossovers between trial arms that perhaps contributed to the perceived net neutral findings for beta-blockers.

Events were also lower than expected, meaning the study was ultimately underpowered and reflective of a low-risk population, cautioned Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City, the ACC session discussant for the study.

Large ongoing studies may be expected to fill in the gaps regarding the question of beta-blockers compared with no beta-blockers or early beta-blocker discontinuation in the MI setting with people with LVEF >40%. These include , , , , , and ABBREVIATE.

"I would say we would need to wait for these studies before we abandon beta-blockers in post-MI patients," Mehran told Ƶ.

For their study, the REDUCE-AMI investigators enrolled SWEDEHEART registry participants who had obstructive coronary artery disease documented on coronary angiography and came out of an acute MI with a LVEF 50% or higher. The open-label trial was conducted mostly in Sweden.

There were 5,020 people randomized to oral beta-blockers or no beta-blockers. Median age was 65 years in both groups, which also had just over 22% women. ST-segment elevation MI was recorded in approximately 35% of the cohort. Over 6% had a prior PCI and 11% were already on oral beta-blockers.

Of the beta-blocker patients, 62.2% got metoprolol 100 mg daily and the rest bisoprolol 5 mg daily.

As for safety, the two groups shared similar rates of bradyarrhythmia, hypotension, or syncope. Neither group had more asthma or chronic obstructive pulmonary disease hospitalizations, nor hospitalizations due to stroke.

The absence of a clinical advantage to beta-blockers was consistent across prespecified subgroups in REDUCE-AMI.

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    Nicole Lou is a reporter for Ƶ, where she covers cardiology news and other developments in medicine.

Disclosures

REDUCE-AMI was supported by grants from the Swedish Research Council, the Swedish Heart Lung Foundation, the Stockholm County Council, the Green Lane Research and Educational Fund, the Estonian Research Council, and Region Stockholm.

Yndigegn and Eagle had no disclosures.

Steg disclosed consulting to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Novartis, Novo Nordisk, PhaseBio, Sanofi; and serving on data and safety monitoring for Sanofi.

Mehran reported many ties to industry, including getting consultant fees/honoraria from Cine-Med Research Institute, Esperion Science, Ionis Pharma, Novartis, Novo Nordisk, Penumbra, Protembis, Radcliffe, Vectura, Vox Media; and having equity in ControlRad.

Primary Source

American College of Cardiology

Yndigegn T, et al "Beta-blockers after myocardial infarction and preserved ejection fraction" ACC 2024.

Secondary Source

New England Journal of Medicine

Steg PG "Routine beta-blockers in secondary prevention -- on injured reserve" N Engl J Med 2024; DOI: 10.1056/NEJMe2402731.