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Beta-blockers Do Not Lower Mortality After Myocardial Infarction With Preserved Ejection Fraction
1. In this randomized controlled trial, long-term beta-blockers did not impact all-cause mortality among patients with preserved left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) and early angiography.
2. Long-term beta-blocker therapy was not associated with a higher risk of adverse events compared to no beta-blocker.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Beta-blockers are a mainstay therapy for heart failure with reduced LVEF. Although historical evidence generally suggested the mortality benefits of beta-blockers following an MI, this predated the diagnostic and therapeutic advancements available today. Furthermore, evidence for beta-blocker therapy specifically for patients with preserved LVEF following acute MIs, especially with early revascularization, is lacking. This trial investigated the effects of long-term beta-blocker therapy against no beta-blocker in patients with an acute MI following coronary angiography who had LVEF ≥50%. At 3.5 years median follow-up, beta-blocker treatment was shown to not impact the risks of death from any cause, new MI, or hospitalization for atrial fibrillation or heart failure, compared to no beta-blocker. Beta-blocker therapy was also not associated with an increased risk of adverse events, including hospitalizations for bradycardia, stroke, or asthma. The study was limited by a lack of blinding and potential for crossover intrinsic to its open-label, pragmatic design. Nevertheless, these findings provided generalizable evidence that beta-blockers did not reduce the composite risk of all-cause mortality or new MI among patients with preserved ejection fraction following an acute MI.
Click here to read the study in NEJM
In-Depth [randomized controlled trial]: This was a randomized, open-label, pragmatic trial to evaluate the impact of long-term beta-blocker therapy initiated early in patients with preserved LVEF. Adult patients were eligible for inclusion at one to seven days after an acute MI if they had undergone coronary angiography demonstrating obstructive coronary disease and had a preserved LVEF (≥50%) demonstrated on echocardiogram. Exclusion criteria included any indication for or contraindication to beta-blocker therapy. From 2017 to 2023, 5020 patients were enrolled and randomized 1:1 to start beta-blocker therapy (either metoprolol targeting 100mg daily or bisoprolol targeting 5mg daily) during their hospitalization or receive no beta-blockers. Patients in the no-beta-blocker group were discouraged from using beta-blockers if there were no other indications than secondary MI prevention. The primary outcome was a composite of death from any cause and a new MI. With the median follow-up of 3.5 years, the composite primary outcome occurred in 7.9% of the beta-blocker group and 8.3% of the no-beta-blocker group (hazard ratio [HR], 0.96; 95% Confidence Interval [CI], 0.79 to 1.16; p=0.64). Correspondingly, the rates of secondary outcomes were similar between the beta-blocker and the no-beta-blocker groups, respectively: death from any cause (3.9% vs. 4.1%; HR, 0.94; 95% CI, 0.71 to 1.24), death from cardiovascular causes (1.5% vs. 1.3%; HR, 1.15; 95% CI, 0.72-1.84), MI (4.5% vs. 4.7%; HR, 0.96; 95% CI, 0.74 to 1.24), hospitalization for atrial fibrillation (1.1% vs. 1.4%; HR, 0.79; 95% CI, 0.48 to 1.31), and hospitalization for heart failure (0.5% vs. 0.9%; HR, 0.91; 95% CI, 0.50 to 1.66). Overall, among patients who had a preserved LVEF following an acute MI, beta-blockers did not impact the composite risk of death from any cause or new MI.
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Is Prescribing Beta-blockers Following A Heart Attack Necessary?
Heart attacks are a leading cause of death, and according to the American Heart Association (AHA), more than 600,000 people experience their first heart attack each year.
Researchers based in Sweden conducted a trial to determine whether the standard practice of prescribing beta-blockers after a heart attack improved the risk of a future cardiovascular event or death.
Prescribing beta-blockers in this circumstance is a common practice, but the researchers say the practice may be outdated.
In the REDUCE-AMI trial, the scientists randomly assigned participants to receive a beta-blocker after they were diagnosed with preserved ejection fraction following a heart attack, also called a myocardial infarction.
The findings showed no significant difference in cardiovascular outcomes between the beta-blockers group and the no-beta-blockers group.
The trial abstract appears in the New England Journal of Medicine.
Beta-blockers are commonly prescribed following a heart attack to reduce the risk of a subsequent cardiovascular event.
A heart attack occurs when a blockage in a coronary artery causes a lack of blood flow to part of the heart. Typically, coronary heart disease, a buildup of plaque in the arteries, causes heart attacks.
While heart attacks are sometimes "silent," the AHA notes they often cause symptoms including:
One measurement of heart health is a person's ejection fraction — this refers to how well the left ventricle of the heart pushes out blood. If someone's measurement is low, it can indicate heart failure.
In the REDUCE-AMI trial, scientists wanted to find out if beta-blockers reduce the risk of death or another heart attack in people who had a heart attack but still had a normal ejection fraction.
The trial began in September of 2017 and lasted through May of 2023. During that time, the researchers recruited 5,020 people from 45 healthcare centers to participate in the study.
In addition to needing a normal heart ejection fraction, participants also had to have a coronary angiography during their hospital stay. The scientists randomly assigned which participants would take a beta-blocker (metoprolol or bisoprolol) as a long-term treatment and had a median follow-up of 3.5 years.
The scientists learned that the beta-blockers provided no overall benefit to these participants, as any-cause death in the beta-blocker group was 3.9%, and death in the group that did not receive a beta-blocker was 4.1%.
In the beta-blocker group, 7.9% of the participants experienced what the scientists classified as a "primary outcome" of either death or a new heart attack.
This is only slightly lower than the primary outcomes in the no-beta-blockers group, which was 8.3% of the participants either dying or having a new heart attack.
The scientists do not consider this small difference to be statistically significant.
After taking a closer look at the data, the scientists found that beta-blocker treatment showed no significant benefit in preventing any-cause death, which was 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group.
The researchers also saw no improvement in the risk of death from cardiovascular causes or hospitalizations for atrial fibrillation (AFib) and heart failure in people who took beta-blockers.
These findings challenge the conventional belief that beta-blockers are universally beneficial after a heart attack.
Lead study investigator Tomas Jernberg, MD, PhD, a cardiology professor and Head of the Department of Clinical Sciences at Karolinska Institutet in Sweden, spoke to Medical News Today about his research.
"I do think the guidelines will be changed, and the prescription of beta-blockers will go down in patients with a heart attack (myocardial infarction) and a preserved (or normal) heart function, that is, about half of all patients with heart attack," Jernberg said.
However, Jernberg emphasized the study was conducted only in patients with normal heart function following a heart attack and not in people with a reduced ejection fraction.
He noted a limitation of the research is that it was an open study versus placebo-controlled, but said this should not "affect the primary outcome, death or new myocardial infarction."
"For patients with reduced heart function or heart failure, we know that beta-blockers improve survival and symptoms. As a patient, you should never stop taking beta-blockers without first talking to your doctor."
— Tomas Jernberg, lead study investigator
While beta-blockers are helpful for many reasons and can lower heart rate and blood pressure, there are some drawbacks to taking beta-blockers.
Dr. Khashayar Hematpour, a cardiovascular medicine physician with UTHealth Houston Heart & Vascular, discussed the study with MNT and noted that while beta-blockers are "well tolerated overall," some people may experience side effects.
"[Beta-blockers] can commonly cause extra slowing of the heart rate, worsening of heart failure and asthma, depression, headaches and dizziness," Hematpour said.
"They can also cause a few other side effects that are not as common, including Raynaud's phenomenon and hepatitis."
Other side effects of beta-blockers may include:
Dr. Cheng-Han Chen, board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, California, spoke with MNT about the study.
"This single study may not immediately change our long-standing practice regarding beta-blockers in patients with normal left ventricular function after myocardial infarction, but other similar trials are ongoing which are examining this same question," Chen said.
"Our clinical practice may indeed change if these other trials also show absence of benefit in this population," he added.
Chen added that not prescribing beta-blockers to patients with normal heart function could reduce the stress of medication management.
"Patients who experience a heart attack may be receiving many new medications as part of a new drug regimen. These patients sometimes have difficulty in managing all of these new medicines, and streamlining drugs that are not beneficial can potentially help patients improve their compliance to a new regimen."
— Cheng-Han Chen, cardiologist
Hematpour said that while the study was a " very well-executed clinical investigation" he noted a weakness in its findings.
"The physicians and patients were both aware whether or not a particular person was receiving beta-blockers. This potentially opens the results to a particular bias," Hematpour said.
Myocardial Infarction
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