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

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.