Beta-Blockers for Secondary Prevention following Myocardial Infarction in Patients Without Reduced Ejection Fraction or Heart Failure: An Updated Meta-Analysis.

Aim: The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blockers (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: We searched 6 databases from Jan 1, 2000 to Sep 1, 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.

Results: 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 (HR, 0.89; 95% CI, 0.81 to 0.97; I2 = 40%; Figure 1), however with moderate-to-high statistical heterogeneity. Prespecified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85 to 1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01 to 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 to 1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96 to 1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01 to 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.