What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Acute myocardial infarction with preserved or mildly reduced ejection fraction (n=19826). Intervention: Beta-blocker therapy vs. No beta-blocker therapy. Primary outcome: Major adverse cardiovascular events (MACE) (RR 0.95, 95% CI 0.87-1.03, p=0.20).

June 20, 2026Open Access

Treatment Effect of Beta-Blocker Therapy After Acute Myocardial Infarction With Preserved or Mildly Reduced Ejection Fraction: A Systematic Review and Trial Sequential Analysis

CCChristopher Chinnatambi LSLouise SakowskiNavicent Health AOAbdul-Rahaman Adedolapo OttunThe University of Texas of the Permian Basin

Key Result

Beta-blocker therapy did not significantly reduce major adverse cardiovascular events compared to no beta-blocker therapy in patients with acute myocardial infarction and LVEF ≥40% (RR 0.95, p=0.20).

Key Points

Evaluate the efficacy and safety of beta-blockers versus no therapy after acute myocardial infarction in patients with preserved or mildly reduced left ventricular ejection fraction.
Systematic review of randomized controlled trials (RCTs) comparing beta-blocker therapy in acute myocardial infarction patients with preserved LVEF (≥50%) or mildly reduced LVEF (40-49%)
Four RCTs involving 19,826 patients were included in the analysis
Trial sequential analysis was performed to assess the conclusiveness of the evidence.
Beta-blockers did not significantly reduce major adverse cardiovascular events (MACE) with a relative risk (RR) of 0.95 (95% CI 0.87-1.03)
No differences were observed in all-cause mortality (RR 0.98, 95% CI 0.86-1.13) and other secondary outcomes
Trial sequential analysis indicated that cumulative evidence for mortality and revascularization outcomes was conclusive, but uncertainty remains for composite outcomes.

Study Design

Type

Meta-Analysis (n=19,826)

Blinding

Open-label

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does beta-blocker therapy reduce major adverse cardiovascular events in patients after acute myocardial infarction with preserved or mildly reduced ejection fraction?

Population

19,826 adults with acute myocardial infarction and preserved or mildly reduced ejection fraction (LVEF ≥ 40%), followed for a weighted median of 3.6 years.

Intervention

Beta-blocker therapy

Comparator

No beta-blocker therapy

Outcome

Major adverse cardiovascular events (MACE)composite

Routine beta-blocker therapy after acute myocardial infarction in patients with preserved or mildly reduced LVEF does not significantly reduce MACE, mortality, or arrhythmias.

Main Result

Relative Risk: 0.95 (95% CI 0.87–1.03)

Absolute Event Rate: 10.3% vs 10.9%

Absolute Risk Reduction: 0.6%

Number Needed to Treat: 167

p-value: p=0.20

Limitations

Trial-level meta-analysis lacking individual patient data for more granular risk stratification
Modest number of included studies limiting power for rare outcomes such as stroke and malignant ventricular arrhythmia
Variability in MACE definitions across trials introduces clinical heterogeneity
Subgroup findings for patients with LVEF 40-49% are limited by power and lack of significant interaction testing
Background medical therapy and revascularization strategies were not identical across studies
Median follow-up duration may not capture very early or late treatment effects
Trial sequential analysis depends on prespecified assumptions regarding effect size and statistical thresholds

Abstract

Long-term use of beta-blockers has been the standard of care after acute myocardial infarction (AMI), but evidence comes largely from pre-reperfusion-era trials in patients with reduced left ventricular ejection fraction (LVEF). With modern reperfusion and optimal secondary prevention, the benefit in patients with preserved and mildly reduced LVEF remains uncertain. Most guidelines continue to recommend routine beta-blocker use in this population, yet no prior meta-analysis has been restricted to recent randomized controlled trials (RCTs). The objective of this article was to evaluate the efficacy and safety of beta-blocker versus no beta-blocker therapy after AMI in patients with preserved or mildly reduced LVEF. The Cochrane Central, PubMed, Embase, and ClinicalTrials.gov were searched for RCTs that compared beta-blocker versus no beta-blocker therapy after AMI in patients with preserved LVEF (≥50%) or mildly reduced LVEF (40-49%). The primary outcome was major adverse cardiovascular events (MACE); secondary outcomes included all‑cause mortality, cardiac death, myocardial infarction (MI), unplanned revascularization, heart failure (HF) events, malignant ventricular arrhythmia, and stroke. Trial sequential analysis (TSA) was performed to assess the conclusiveness of the evidence and whether further trials are warranted. Four RCTs comprising 19,826 patients (BB (beta blocker), n = 9892; no BB, n = 9934) were included. Beta-blockers did not significantly reduce MACE (RR 0.95, 95% CI 0.87-1.03). No difference was observed in all-cause mortality (RR 0.98, 95% CI 0.86-1.13), cardiac death (RR 1.15, 95% CI 0.88-1.51), MI (RR 0.88, 95% CI 0.75-1.04), unplanned revascularization (RR 1.01, 95% CI 0.88-1.16), HF events (RR 0.83, 95% CI 0.64-1.08), malignant ventricular arrhythmia (RR 0.84, 95% CI 0.47-1.50), or stroke (RR 1.18, 95% CI 0.85-1.64). Heterogeneity was low across outcomes. TSA demonstrated that the cumulative evidence for all-cause mortality, unplanned revascularization, and malignant ventricular arrhythmia was conclusive, while MACE and other outcomes remain inconclusive. In AMI patients with preserved or mildly reduced LVEF, beta-blockers did not reduce ischemic events, mortality, or arrhythmia. TSA suggests that additional trials are unlikely to alter conclusions for mortality and revascularization, but uncertainty persists for composite outcomes.

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