For decades, clinicians have routinely prescribed beta-blockers to patients recovering from acute myocardial infarction (MI). Two new randomized trials published in The New England Journal of Medicine challenge this practice in patients with preserved left ventricular ejection fraction (LVEF). The findings indicated that beta-blockers remain safe in this group but may not provide consistent benefits, prompting a shift toward individualized decision-making.

The BETAMI-DANBLOCK trial combined two nearly identical trials conducted in Denmark and Norway. Together, they enrolled 5574 patients (mean age, 63 years; 20.8% women) with MI in the previous 7 or 14 days and with an LVEF of at least 40%. Coronary revascularization was required for BETAMI but not for DANBLOCK.

After a median follow-up of 3.5 years, the composite endpoint of death from any cause, MI, unplanned revascularization, ischemic stroke, heart failure, or ventricular arrhythmias occurred in 14.2% of those treated with beta-blockers and 16.3% of those who weren’t (hazard ratio [HR], 0.85; 95% CI, 0.75-0.98). The benefit was mainly driven by a lower risk for MI (HR, 0.73; 95% CI, 0.59-0.92), although most endpoints, except for ischemic stroke, favored the treatment.

In contrast, the open-label REBOOT-CNIC trial was an investigator-initiated study funded by Centro Nacional de Investigaciones Cardiovasculares Carlos III. The trial enrolled 8438 patients (mean age, 61 years; 19.3% women) with acute MI, with or without ST-segment elevation, and with LVEF greater than 40% at 109 centers in Spain and Italy. The participants were randomly assigned to receive beta-blockers or no beta-blockers.

After a median follow up of 3.7 years, there was no significant difference in the risk for death from any cause, reinfarction, or hospitalization for heart failure (22.5% vs 21.7%; HR, 1.04; 95% CI, 0.89-1.22). Secondary outcomes, including all-cause mortality, reinfarction, and heart failure hospitalization, were analyzed individually and showed no significant differences.

Both trials confirmed that beta-blockers are safe for patients with preserved LVEF.

Explaining Discrepancies

The differing outcomes in BETAMI-DANBLOCK and REBOOT-CNIC reflect important contrasts in design and contemporary MI care. BETAMI-DANBLOCK used a broader composite endpoint that captured a wider range of ischemic and arrhythmic events, increasing the sensitivity to detect treatment effects. This population also had a higher baseline ischemic risk.

REBOOT-CNIC used a narrower primary endpoint with fewer total events, reducing statistical power. More comprehensive revascularization, intensive antithrombotic therapy, and lower baseline cardiovascular risk would likely further narrow the opportunity to detect a treatment benefit.

Together, these trials support a consistent conclusion: Beta-blockers are safe in patients with preserved LVEF, but routine prescribing offers uncertain benefits. They remain appropriate for residual angina, persistent tachycardia, clinically significant arrhythmias, and elevated ischemic risk. Omission is reasonable in stable, asymptomatic patients who have undergone complete revascularization and have preserved LVEF.

These findings reinforce the need for individualized treatment. Beta-blocker use after MI in patients with preserved LVEF should reflect each patient’s clinical profile and residual risk rather than historical routines.

This story was translated and adapted from El Medico Interactivo, part of the Medscape Professional Network.