EBM BLS: Beta-blockers Fail to Improve Cardiovascular Outcomes in Patients with Myocardial Infarction and Preserved Ejection fraction

Source Article: Yndigegn T, Lindahl B, Mars K, et al. Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med. 2024;390(15):1372-1381. doi:10.1056/NEJMoa2401479

WHY THIS IS IMORTANT

• Despite substantial progress in medical and interventional therapy, coronary artery disease (CAD) remains the leading cause of death in the United States.¹

• Early trials showed mortality benefit from beta-blockers after myocardial infarction (MI). However, these studies predated the advent of aspirin, percutaneous coronary intervention (PCI), statins, and P2Y12 inhibitors.

• Recent observational studies have not found an association between beta-blockers and mortality for patients with preserved ejection fraction (EF) post-MI.²

• The ABYSS trial found that discontinuing beta-blockers was associated with higher rates of adverse cardiac events; however, the number of deaths and MI was similar between groups and the difference in outcomes was driven by cardiac hospitalization.³

INTERVENTION

• 5,020 participants were randomized in 1:1 ratio to beta-blockers (metoprolol or bisoprolol) or usual care.

• The primary endpoint was a composite of death from any cause or MI. Secondary outcomes were cardiovascular death, hospitalization for atrial fibrillation and heart failure.

• Safety endpoints included hospitalizations for stroke, bradycardia, atrioventricular block, hypotension, syncope, or pacemaker implantation (Fig. 1).

Figure 1.

Death and myocardial infarction at follow-up.

RESULTS

• Median age was 65 years, 78% male, 35% presented with ST-elevation MI, and 95% were from Sweden.

• Most participants had single- or two-vessel disease (82.7%), and nearly all received PCI (95.8%).

• Participants were followed for a median of 3.5 years.

• Crossover occurred in 18.1% of participants in the beta-blocker arm and 14.3% in the usual care arm.

• The primary outcome of death or recurrent myocardial infarction occurred in 7.9% of beta-blocker patients and 8.3% of usual-care (HR 0.96; 95% CI 0.79–1.16).

• Secondary outcomes of cardiovascular death (1.5% vs 1.3%), hospitalizations for atrial fibrillation (1.1% vs 1.4%) and for heart failure (0.8% vs 0.9%) were similar.

• Safety endpoints were also similar including hospitalization for bradycardia, AV block, hypotension, or syncope (3.4% vs 3.2%), stroke (1.4% vs 1.8%), and hospitalization for asthma or COPD (0.6% vs 0.6%).

• Results of the primary outcome were similar across all prespecified subgroups.

STUDY DESCRIPTION

Setting

• This was a pragmatic, randomized, open-label, intention-to-treat, superiority trial at 45 centers in Sweden, Estonia, and New Zealand.

• Inclusion criteria: Adult patients within 1 week of MI with obstructive CAD on angiography and EF > 50%.

• Exclusion criteria: Patients with an additional indication for or contraindication to beta-blockers were ineligible.

Methods

• Participants were randomized in a 1:1 ratio to receive beta-blockers in the hospital and receive a prescription for cardioselective beta-blockers (metoprolol or bisoprolol) after discharge.

• Control patients were discouraged from using beta-blocker unless other indications arose.

• Data was collected from national registries. Diagnoses of myocardial infarction were verified by principal investigators using a standardized checklist.

• This study was unblinded. The investigators commented that blinding was not deemed feasible because of the pragmatic, registry-based design.

• The study was powered at 80% to detect a 25% reduction in composite primary outcome, corresponding to a 0.9% absolute risk reduction.

STUDY QUALITY AND APPLICATION TO PATIENTS

• Strengths of the study include its large scale, randomization, and intention-to-treat design.

• Limitations included lack of blinding, majority white male patient population, moderate rates of crossover, outcomes collected via registry, and lack of central adjudication committee.

• Almost all participants received indicated medical therapy for secondary prevention.

• The findings are consistent with the ABYSS trial which reported similar results for death and MI.⁴

• This study suggests that beta-blockers are not required therapy for post-MI patients with preserved EF > 50%. Meta-analyses of contemporary RCTs support continued use in those with EF 40–49% for reducing all-cause mortality, recurrent MI, and heart failure.⁴

• Findings may not apply to patients who did not undergo PCI or to those at highest risk, including patients with three-vessel disease.

• Beta-blockers remain a first-line treatment for stable angina and heart failure with reduced ejection fraction.

Author Contributions 

All authors contributed to the conception and design of this manuscript. 

Funding

We have no funding related to this submission.

Data Availability

All data analyzed are contained within the cited manuscript.

Declarations

Human Ethics and Consent to Participate Declarations

Not applicable. The manuscript is a summary and analysis of a previously published journal article. No original research involving human subjects was conducted, and therefore IRB approval is not required. There are no potential ethical issues associated with this submission.

Conflicts of interest

We have no conflicts of interest to disclose.