Long-term oral β-blocker therapy, including bisoprolol, metoprolol, and carvedilol, reduces the composite endpoint of all-cause death, new myocardial infarction, or heart failure by 25% in patients with MI and mildly reduced left ventricular ejection fraction (LVEF 40-49%), a meta-analysis has reported.The meta-analysis of four randomized controlled trials (REBOOT, BETAMI, DANBLOCK, and CAPITAL-RCT) published in The Lancet included 1,885 patients with acute MI and mildly reduced LVEF during index hospitalization. Of these, 991 patients were assigned to β-blockers and 894 to control (no β-blockers); where bisoprolol was used in 430 patients (44%), metoprolol in 485 patients (49%), and carvedilol in 46 patients (5%).The key findings of the study include:β-blocker therapy reduced the composite endpoint of all-cause death, new myocardial infarction, or heart failure by 25%, with events occurring in 11% of patients compared to 14% in the no β-blocker group (β-blocker group: 32.6 events per 1,000 patient-years vs no β-blocker group: 43.0 events per 1,000 patient-years; HR 0.75, 95% CI 0.58-0.97; p=0.031) [as shown in Figure 1].Figure 1: Cumulative Incidence of Primary Endpoint Over Timeβ-blocker therapy reduced all-cause death by 22%, with mortality of 6% compared to 8% in the no β-blocker group (β-blocker group: 17.1 events per 1,000 patient-years vs no β-blocker group: 21.9 events per 1,000 patient-years; HR 0.78, 95% CI 0.55-1.11; p=0.169).β-blocker therapy reduced cardiac death by 45%, occurring in 2% of patients compared to 3% in the no β-blocker group (β-blocker group: 5.6 events per 1,000 patient-years vs no β-blocker group: 10.1 events per 1,000 patient-years; HR 0.55, 95% CI 0.28-1.06; p=0.076).β-blocker therapy reduced new myocardial infarction by 23%, occurring in 4% of patients compared to 5% in the no β-blocker group (β-blocker group: 11.8 events per 1,000 patient-years vs no β-blocker group: 15.1 events per 1,000 patient-years; HR 0.77, 95% CI 0.50-1.18; p=0.230)β-blocker therapy reduced heart failure occurrence by 29%, occurring in 3% of patients compared to 4% in the no β-blocker group (β-blocker group: 9.0 events per 1,000 patient-years vs no β-blocker group: 12.7 events per 1,000 patient-years; HR 0.71, 95% CI 0.44-1.14; p=0.152)The analysis also revealed that the therapeutic benefit emerged at approximately 3 months after initiation of β-blocker therapy and continued to accrue throughout the study duration (median follow-up 3.5 years, IQR 2.3-4.5). This pattern of sustained separation of survival curves suggests that the clinical benefit derives from long-term continuous therapy rather than acute protective effects alone.The benefit of β-blocker therapy was remarkably consistent across all four trials (REBOOT, BETAMI, DANBLOCK, and CAPITAL-RCT) with no evidence of heterogeneity (Cochran’s Q test p=0.95, I²=0%). No evidence of heterogeneity in treatment effects by sex, type of myocardial infarction, LVEF category, β-blocker dosage, or country Spain, Italy, Norway, Denmark, and Japan (p interaction=0.98), demonstrating the universal applicability of these findings across diverse healthcare settings. The safety analysis demonstrated no significant increase in adverse events with β-blocker therapy. (Figure 2)Figure 2: Forest Plot – Effect Estimates for Primary, Secondary, and Safety Endpoints Note for Client: HCP Bytes will be added here Proposed Questions for HCPs1. For few years now, post-MI patients with mildly reduced LVEF (40–49%) have sat in a therapeutic grey zone. Does this study findings finally justify treating this group more like HFrEF rather than preserved EF when it comes to long-term β-blocker therapy? What practical implications could these indicate for clinicians? 2. The meta-analysis shows 30% of MI patients fall into the LVEF 40-49% range. In your practice, are you routinely prescribing β-blockers to these patients, or do you reserve them primarily for reduced EF cases? What’s been your experience with clinical outcomes in this intermediate ejection fraction group?3. The median follow-up was 3.5 years with ongoing benefits in the current study. In your practice, how long do you typically continue β-blocker therapy in post-MI patients with mildly reduced EF? Do you reassess LVEF periodically and consider stopping if it normalizes, or continue indefinitely? 4. Beyond mortality, there’s a 29% reduction in new heart failure cases. Should we be considering β-blockers more as a heart failure prevention strategy in post-MI patients with LVEF 40-49%? How does this change our conversation with patients about long-term adherence? 5. This meta-analysis used bisoprolol in 44% of patients, metoprolol in 49%, and carvedilol in 5%. Given that bisoprolol is highly cardio-selective with a metabolically neutral profile, how does this influence your choice in patients with comorbidities like diabetes or mild bronchial reactivity—conditions we commonly see in Indian patients? This meta-analysis provides evidence that β-blocker therapy significantly reduces MACE by 25% in post-myocardial infarction patients with mildly reduced LVEF (40-49%), a population representing up to 30% of all MI patients.Abbreviations: AHA = American Heart Association, ACC = American College of Cardiology, AV = Atrioventricular, BETAMI = Beta-blocker Treatment After acute Myocardial Infarction in patients without reduced left ventricular ejection fraction, CAPITAL-RCT = CArvedilol Post-Infarction survivaL controL In Left ventricular dysfunction – Randomized Controlled Trial, CI = Confidence Interval, DANBLOCK = DANish-norwegian trial on Beta-blocker therapy after myocardial infarction with preserved ejection fraction, ESC = European Society of Cardiology, HR = Hazard Ratio, IQR = Interquartile Range, LVEF = Left Ventricular Ejection Fraction, MI = Myocardial Infarction, PCI = Percutaneous Coronary Intervention, REBOOT = tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTionReference: Rossello X, Prescott EIB, Kristensen AMD, Latini R, Fuster V, Fagerland MW, Pocock SJ, Halvorsen S, Dominguez-Rodriguez A, Holmager TLF, Sanchez PL, Bakken A, Raposeiras-Roubin S, Jensen SE, Kimura T, Ottani F, Lambrechtsen J, Anguita M, Ozasa N, Atar D, Ibanez B, Munkhaugen J. β blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysis of randomised controlled trials. Lancet. 2025 Sep 13;406(10508):1128-1137. doi: 10.1016/S0140-6736(25)01592-2.