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Meta-Analysis
. 2025 Jun 3;32(8):633-646.
doi: 10.1093/eurjpc/zwae298.

Beta-blockers for secondary prevention following myocardial infarction in patients without reduced ejection fraction or heart failure: an updated meta-analysis

Kuan-Yu Chi  1 , Pei-Lun Lee  1 , Ishmum Chowdhury  1 , Zafer Akman  2 , Sridhar Mangalesh  1 , Junmin Song  1 , Vikyath Satish  1 , Golsa Babapour  3 , Yi-No Kang  4 , Rachel Schwartz  5 , Yu Chang  6 , Pawel Borkowski  1 , Michele Nanna  7 , Abdulla A Damluji  8 , Michael G Nanna  3
Affiliations
Meta-Analysis

Beta-blockers for secondary prevention following myocardial infarction in patients without reduced ejection fraction or heart failure: an updated meta-analysis

Kuan-Yu Chi et al. Eur J Prev Cardiol. .

Abstract

Aims: The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blocker (BB) use post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). We aimed to address the heterogeneity in contemporary data around BB post-MI in this population.

Methods and results: We searched six databases from 1 January 2000 to 1 September 2024 to identify contemporary studies enrolling MI patients without reduced EF (≤40%) or history of HF receiving BB at index MI and comparing outcomes between BB users and non-users. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular (CV) mortality. Random-effects meta-analysis was conducted using the restricted maximum likelihood method. There were 24 studies including 290 349 patients enrolled in the contemporary era. Overall, BB use was associated with a significant 11% reduction in all-cause mortality [hazard ratio (HR), 0.89; 95% confidence interval (CI), 0.81-0.97; I2 = 40], however with moderate-to-high statistical heterogeneity. Pre-specified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94-1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85-1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01-1.52; I2 = 0%) in patients with a 1-year event-free period, defined as no death, recurrent MI, or HF while on BB following index MI. In patients with no event-free period, meta-regression revealed that BB mortality benefits were modified by the study inclusion period (P = 0.01), reflecting a temporal trend of decreasing BB mortality benefits over time. Based on the temporal trend, in patients with preserved EF post-2010, BB exhibited no reduction in all-cause mortality (HR, 0.97; 95% CI, 0.90-1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96-1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01-1.52; I2 = 0%).

Conclusion: In the contemporary reperfusion era, BB may not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, post-MI BB use was associated with detrimental effects in patients with preserved EF.

Keywords: Beta-blockers; Ejection fraction; Heart failure; Mortality; Myocardial infarction.

Plain language summary

Our study aimed to synthesize current evidence around post-myocardial infarction (MI) beta-blocker (BB) use in patients without reduced ejection fraction (EF) or heart failure (HF). We reveal that the mortality benefits of BB are modified by three factors, namely an event-free period, study inclusion period, and EF.In patients on BB post-MI with 1 year free of death, recurrent MI, or HF, there may not be additional mortality benefit to continuing the BB.For patients included after 2010, BB did not offer mortality benefits and may even be harmful in those with preserved EF.In contrast to those with preserved EF, patients with mildly reduced EF derive mortality benefits from BB.

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Conflict of interest statement

Conflict of interest: M.G.N. reports current research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute (PCORI), and the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342). M.G.N. also reports being a consultant for HeartFlow, Novo Nordisk, and Merck. A.A.D. receives research funding from (i) the Pepper Scholars Program of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center funded by the National Institute on Aging P30-AG021334; (ii) mentored patient-oriented research career development award from the National Heart, Lung, and Blood Institute K23-HL153771; (iii) The NIH National Institute of Aging R01-AG078153; and (iv) the Patient-Centered Outcomes Research Institute (PCORI). All other authors report no disclosures relevant to the present work.

Comment in

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