β-Blockers Show No Added Benefit After MI With Preserved LVEF

A meta-analysis of recent clinical trials evaluating β-blockers as treatment for patients with acute myocardial infarction (MI) and preserved left ventricular ejection fraction (LVEF) found this treatment did not provide any additional benefits to this particular group, according to a new research letter published in JAMA Cardiology.¹

The effect of β-blockers on clinical outcomes of patients with MI and mildly reduced LVEF is largely known,² and they remain the pinnacle treatment for patients with MI and reduced LVEF. However, the results from 4 recent clinical trials, CAPITAL-RCT (NCT01155635), REDUCE-AMI (NCT03278509), REBOOT-CNIC (CT03596385), and BETAMI-DANBLOCK (NCT03646357; NCT03778554), produced inconsistent findings in the efficacy of β-blockers in patients with MI and an LVEF greater than 40%. For example, REBOOT-CNIC reported neutral outcomes, whereas BETAMI-DANBLOCK reported beneficial effects. However, the meta-analysis revealed little to no significant differences in clinical outcomes of patients with MI and preserved LVEF and the control group when using β-blockers as treatment.¹

Researchers analyzed data from all 4 trials using the Mantel-Haenszel method to obtain relative risk (RR). The clinical trials included in this meta-analysis were chosen from relevant, randomized clinical trials published up to August 30, 2025. The primary outcomes consisted of all-cause mortality, cardiovascular mortality, MI, heart failure, and unplanned revascularization. The REDUCE-AMI trial was the only trial of the 4 to enroll patients with acute MI and an LVEF greater than 50%. Whereas the other 3 trials enrolled patients with MI and an LVEF greater than 40%. Given the range of LVEF between trials, researchers decided to focus on patients with an LVEF between 40% and 49%.

Combined, all 4 trials included 19,826 patients with median follow-up durations ranging from 3.5 to 5.0 years. Of them, there were 8901 patients in the β-blockers group. Between the β-blockers and the control group, there was no significant difference in cardiovascular mortality (RR, 1.25; 95% CI, 0.94-1.68), MI (RR, 0.89; 95% CI, 0.78-1.03), heart failure (RR, 0.87; 95% CI, 0.64-1.18), or unplanned revascularization (RR, 1.04; 95% CI, 0.87-1.23). Over the course of the follow-up, there were 338 deaths (3.80%) among the 8 β-blocker groups, but no significant difference in deaths between the 2 groups (RR, 1.02; 95% CI, 0.88-1.19).

Overall, the results suggested partial benefits using β-blockers to treat patients with MI and mildly reduced LVEF; they found no association between cardiovascular improvement and β-blockers in patients with preserved LVEF.

“This finding suggests that the extent of myocardial remodeling and baseline left ventricular function may be key determinants of β-blocker efficacy,” authors of the research letter wrote. “Our study raises new considerations regarding the indications for β-blockers.”

The study authors suggested the findings pointed to a ceiling effect caused by optimized background therapies used to treat MI, like early revascularization and optimal medical therapy. They also mentioned that some of the benefits from modern therapies may be reduced in certain populations.

The study was limited by the use of aggregate data from published trials and not individual participant data, thus limiting researchers’ ability to perform subgroup analyses. Additionally, the number of eligible studies was limited, as some trials were not designed to assess outcomes in patients with an LVEF of 50% or greater.

“Future large-scale, well-targeted studies are needed to better define the optimal pharmacologic strategy in this population and to identify potential subgroups that may derive benefit from β-blocker therapy,” the authors concluded.

References

1. Li L, Li J, Jiang S, et al. β-Blockers after myocardial infarction in patients with preserved ejection fraction: a meta-analysis. JAMA Cardiol. Published online January 7, 2026. doi:10.1001/jamacardio.2025.4923

2. Rosello X, Prescot E, Kristensen A, et al. β-Blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysis of randomized controlled trials. LANCET. 2025;406(10508):P1128-1137. doi:10.1016/S0140-6736(25)01592-2