β blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysis of randomised controlled trials

β blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysisof randomised controlled trials

Lancet. 2025 Sep 13;406(10508):1128-1137.

Abstract

Background: The effects of β-blocker therapy on clinicaloutcomes 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 left ventricular ejectionfraction (LVEF ≥40%). However, none were individually powered to assess these effects in the subgroup of patients with mildly reduced left ventricular ejection fraction. We aimed to assess the efficacy of β blockers in patientswith myocardial infarction and mildly reduced left ventricular ejection fraction during the index hospitalisation.

Methods: We conducted an individual patient-levelmeta-analysis of patients with mildly reduced left ventricular ejection fraction 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 left ventricular ejection fraction. 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 heartfailure. All endpoints were independently adjudicated. This meta-analysis was registered with PROSPERO (CRD420251023480).

Findings: 1885 patients with myocardial infarction andmildly reduced left ventricular ejection fraction 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 patientswere 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 theβ-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 thetrials (trial-by-treatment pinteraction=0·95) or between countries of enrolment was observed (pinteraction=0·98).

Interpretation: In patients with acute myocardial infarctionwith mildly reduced left ventricular ejection fraction 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 inpatients with myocardial infarction with reduced left ventricular ejection fraction to the subgroup with mildly reduced left ventricular ejection fraction.

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