Most trials showing a benefit from beta-blocker treatment after a myocardial infarction included patients with large infarctions and were conducted in an era before modern diagnosis of myocardial infarction based on biomarkers, as well as treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists.
In an open-label, parallel-group trial conducted in 45 centers across Sweden, Estonia, and New Zealand, we randomly assigned patients with acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary outcome was a combination of death from any cause or a new myocardial infarction.
From September 2017 to May 2023, a total of 5,020 patients were enrolled (95.4% of them from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7).
A primary outcome event occurred in 199 of 2,508 patients (7.9%) in the beta-blocker group and in 208 of 2,512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; p = 0.64).
Beta-blocker treatment did not appear to lead to a lower cumulative incidence of secondary endpoints (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; cardiovascular death, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%).
Regarding safety outcomes, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or pacemaker implantation occurred in 3.4% of patients in the beta-blocker group and in 3.2% in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease occurred in 0.6% in both groups; and hospitalization for stroke occurred in 1.4% and 1.8%, respectively.
Among patients with acute myocardial infarction who underwent early coronary angiography and had preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary outcome of death from any cause or a new myocardial infarction compared to no beta-blocker use.
Beta-blockers may not benefit many heart attack survivors
A study suggests that routine use is likely unnecessary for those with a normal ejection fraction.
Taking beta-blockers after a heart attack did not significantly reduce the risk of death or a second heart attack among people with normal heart pumping capacity, as indicated by an ejection fraction of 50% or more, according to a study presented at the American College of Cardiology.
The findings call into question the routine use of beta-blockers for all patients after a heart attack, which has been a cornerstone of medical care for decades. Approximately 50% of heart attack survivors do not experience heart failure. Among these patients, the study found no differences in the primary composite outcome of death from any cause or nonfatal new heart attack between those prescribed beta-blockers and those who were not.
“I think, after this study, many doctors will not see an indication to routinely treat all their patients with beta-blockers after a heart attack,” said Troels Yndigegn, MD, an interventional cardiologist at Lund University in Sweden and the study´s lead author. "We believe the evidence still supports beta-blockers in patients with a large myocardial infarction who experience heart failure, but for patients without signs of heart failure and with a normal ejection fraction, this trial establishes that there is no indication that routine beta-blocker use is beneficial."
Heart failure occurs when the heart muscle becomes too weak or stiff to pump blood effectively. It is primarily evaluated in terms of left ventricular ejection fraction, which is the proportion of blood expelled from the left ventricle of the heart with each beat. An ejection fraction above 40%-50% is considered normal.
Beta-blockers lower blood pressure by inhibiting certain hormones, such as adrenaline, that speed up the heart. Many doctors prescribe beta-blockers to all patients after a heart attack, usually for at least a year or often for the rest of the patient´s life, based on evidence that they can help prevent a second heart attack. However, researchers said the clinical trials that led to this routine use of beta-blockers were conducted before the arrival of many newer procedures now widely used to open blocked arteries.
“At that time, the damage to the heart muscle was greater than what we see today, and we didn’t have the ability to revascularize patients with percutaneous coronary intervention and stents like we do today,” Yndigegn said. "What we see today are more myocardial infarctions that are smaller and do not damage the heart muscle to the same extent."
To clarify the potential benefits of beta-blockers considering this changing landscape, the REDUCE-AMI study enrolled 5,020 patients treated for acute heart attacks at 45 centers in Sweden, Estonia, and New Zealand, who participated in the SWEDEHEART Registry. All patients had an ejection fraction of 50% or more, as assessed with an echocardiogram performed within a week after the heart attack. Half were randomly assigned to receive long-term beta-blocker medication, and the rest did not take beta-blockers.
Over a median follow-up of 3.5 years, there were no significant differences between the groups in the rate of the primary composite outcome or in secondary clinical outcomes such as heart failure, atrial fibrillation, or symptoms like chest pain and shortness of breath. There were also no differences in safety outcomes such as stroke, abnormally low blood pressure, or fainting.
Researchers said the lack of benefits associated with beta-blockers observed in this patient group could potentially free many patients from the burden of taking these drugs, allowing them to avoid side effects like mood disorders, fatigue, and sexual dysfunction.
"Many patients report side effects or suspect side effects with these medications, so I think this finding will have an impact on thousands of patients," Yndigegn said.
The study did not involve a placebo control, and participants knew which group they were assigned to. While this open-label approach could introduce bias, the researchers said it was unlikely to affect outcomes like death and heart attacks. Yndigegn said the results should be generalizable beyond the population in which the study was conducted, adding that other observational studies are being conducted to help shed light on the routine use of beta-blockers in various populations.
The researchers plan to separately analyze results related to quality of life and sexual health.
The study was funded by the Swedish Research Council, the Swedish Heart-Lung Foundation, and the Stockholm County Council.
Reference: Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction Troels Yndigegn, Bertil Lindahl, Katarina Mars, Joakim Alfredsson, et al. for the REDUCE-AMI Investigators. NEJM DOI: 10.1056/NEJMoa2401479. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509).
