Beta Blockers Cut CV Events by 25% in Post-MI Patients with Mildly Reduced LVEF: Meta-Analysis

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 Time

• β-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

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Proposed Questions for HCPs

1. 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 fracTion

Reference: 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.