August 30, 2025The Lancet
β blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysis of randomised controlled trials
Xavier RossellóEva PrescottAnna Meta Dyrvig KristensenRoberto LatiniValentı́n FusterMorten Wang FagerlandStuart PocockSigrun HalvorsenAlberto Domínguez‐RodríguezTherese Lucia Friis HolmagerPedro L. SánchezArnhild BakkenSergio Raposeiras‐RoubínSvend Eggert JensenTakeshi KimuraFilippo OttaniJess LambrechtsenManuel AnguitaNeiko OzasaDan AtarBorja IbáñezJohn Munkhaugen
Key result
Beta-blockers cut major composite events ~25% in post-MI patients with mildly reduced LVEF.
- HR 0.75
- 95% CI 0.58-0.97
- P=0.031
- n=1,885
Why the study?
The effects of β-blocker therapy on clinical outcomes in patients with myocardial infarction and mildly reduced LVEF (40-49%) are largely unknown due to lack of adequately powered subgroup analyses.
Does long-term oral beta-blocker therapy reduce the composite of all-cause death, new myocardial infarction, or heart failure in patients with a recent acute myocardial infarction and mildly reduced LVEF (40-49%)?
Key Points
- To evaluate the efficacy of beta-blocker therapy on long-term clinical outcomes in patients presenting with acute myocardial infarction and mildly reduced left ventricular ejection fraction (40–49%) without heart failure.
- Individual patient-level meta-analysis of four randomised controlled trials (REBOOT, BETAMI, DANBLOCK, and CAPITAL-RCT) testing long-term oral beta-blocker therapy initiated within 14 days post-infarction (median follow-up >1 year; PROSPERO CRD420251023480).
- Analyzed 1,885 patients with mildly reduced ejection fraction (40–49%) and no history or signs of heart failure (991 assigned to beta blockers and 894 to control).
- Evaluated the primary composite endpoint of all-cause death, new myocardial infarction, or heart failure using a one-stage, fixed-effects Cox proportional hazards regression model.
- The primary composite endpoint occurred in 106 patients (32·6 events per 1000 patient-years) in the beta-blocker group versus 129 patients (43·0 per 1000 patient-years) in the no beta-blocker group (hazard ratio 0·75 [95% CI 0·58–0·97]; p=0·031).
- Treatment effects were consistent across studies with no observed heterogeneity between trials (trial-by-treatment pinteraction=0·95) or across countries of enrolment (pinteraction=0·98).
Study Design
Type
Meta-Analysis (n=1,885)
Blinding
Open-label
Randomization
Randomized controlled trials
Multicenter
Yes
Structured PICO
Does long-term oral beta-blocker therapy reduce the composite of all-cause death, new myocardial infarction, or heart failure in patients with a recent acute myocardial infarction and mildly reduced LVEF (40-49%)?
P
Population
1,885 patients with acute myocardial infarction and mildly reduced LVEF (40-49%) without history of heart failure, pooled from 4 randomized controlled trials and followed for a median of >1 year.
I
Intervention
Oral beta-blocker therapy.
C
Comparator
Control group receiving no beta-blocker therapy.
O
Outcome
Composite of all-cause death, new myocardial infarction, or heart failure assessed via a Cox proportional hazards regression model.composite
Main Result
Hazard Ratio: 0.75 (95% CI 0.58–0.97)
Absolute Event Rate: 32.6% vs 43%
p-value: p=0.031
This meta-analysis demonstrates that long-term beta-blocker therapy reduces major adverse cardiovascular events in post-MI patients with mildly reduced ejection fraction (40-49%), extending the established benefits previously restricted to those with LVEF <40%.
Limitations
- Derived from a relatively limited population pool
- The 40-49% category reflects predefined strata rather than an established biological threshold
- Open-label design of the included contemporary trials introduces potential for treatment crossover
- Optimal timing of initiation not directly addressed due to varied randomization windows across trials
- Relatively limited population sample for the 40-49% LVEF subgroup
- LVEF 40-49% reflects predefined strata rather than an established biological threshold
- Open-label design of the contributing trials may influence event rates and allows for treatment crossover
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Our findings extend the known benefits of these agents in MI patients with reduced LVEF to the subgroup with mildly reduced LVEF. Further research should now focus on patients with preserved LVEF (>50%).”
“However, subgroup analyses and a supporting meta-analysis indicate that patients with moderately impaired LV function may still benefit from beta-blocker therapy. This subgroup warrants separate evaluation in future studies until more definitive conclusions can be drawn.”
Implication
Supports beta-blocker use after MI with LVEF 40-49%; extends prior mortality benefit shown only for LVEF <40%.
Abstract
BACKGROUND The effects of β-blocker therapy on clinical outcomes in patients with myocardial infarction and mildly reduced (40-49%) left ventricular ejection fraction (LVEF) are largely unknown. Four recently conducted randomised trials tested the efficacy of β blockers after a recent myocardial infarction in patients without reduced LVEF (LVEF ≥40%). However, none were individually powered to assess these effects in the subgroup of patients with mildly reduced LVEF. We aimed to assess the efficacy of β blockers in patients with myocardial infarction and mildly reduced LVEF during the index hospitalisation. METHODS We conducted an individual patient-level meta-analysis of patients with mildly reduced LVEF and no history or signs of heart failure from four recent clinical trials. These studies were included because they were randomised controlled trials testing long-term effects (median follow-up >1 year) of oral β-blocker therapy in patients who recently had a myocardial infarction (randomisation within 14 days) and had mildly reduced LVEF. No further studies were found in a systematic review (Jan 1, 2020 to June 26, 2025). A one-stage, fixed-effects, Cox proportional hazards regression model was used to assess the treatment effect of β blockers on the predefined primary composite endpoint of all-cause death, new myocardial infarction, or heart failure. All endpoints were independently adjudicated. This meta-analysis was registered with PROSPERO (CRD420251023480). FINDINGS 1885 patients with myocardial infarction and mildly reduced LVEF were included in the meta-analysis: 979 from the REBOOT trial, 422 from the BETAMI trial, 430 from the DANBLOCK trial, and 54 from the CAPITAL-RCT trial. Overall, 991 patients were assigned to β blockers and 894 to control (no β blockers). The primary composite endpoint occurred in 106 patients (32·6 events per 1000 patient-years) in the β-blocker group and 129 patients (43·0 per 1000 patient-years) in the no β-blocker group (hazard ratio 0·75 [95% CI 0·58-0·97]; p=0·031). No heterogeneity between the trials (trial-by-treatment pinteraction=0·95) or between countries of enrolment was observed (pinteraction=0·98). INTERPRETATION In patients with acute myocardial infarction with mildly reduced LVEF without history or clinical signs of heart failure, β-blocker therapy was associated with a reduction in the composite of all-cause death, new myocardial infarction, or heart failure. These results extend the known benefits of these agents in patients with myocardial infarction with reduced LVEF to the subgroup with mildly reduced LVEF.
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Cite This Study
Rosselló et al. (2025) conducted a meta-analysis in Acute myocardial infarction with mildly reduced ejection fraction (40-49%) (n=1,885). Beta-blockers vs. Control (no beta-blockers) was evaluated on Composite of all-cause death, new myocardial infarction, or heart failure (HR 0.75, 95% CI 0.58-0.97, p=0.031). Beta-blocker therapy reduced the primary composite endpoint of all-cause death, new myocardial infarction, or heart failure by 25% (HR 0.75) compared to no beta-blockers in patients with acute myocardial infarction and mildly reduced LVEF (40-49%).