Mortality effects of beta-blockers on myocardial infarction in patients without reduced ejection fraction or heart failure in the contemporary reperfusion era : a systematic review and meta-analysis

Abstract

Abstract Background The 2023 ESC and AHA/ACC guidelines note that contemporary data are heterogenous regarding the use of beta-blockers (BB) post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). Purpose We performed a systematic review and meta-analysis to address the heterogeneity in existing literature around BB post-MI in patients without HF. Methods We searched 6 databases from Jan 1, 2000 to Jan 12, 2024 to identify modern randomized controlled trials (RCTs) or observational studies enrolling MI patients without reduced EF or history of HF who received BB at index MI, and comparing outcomes between BB users and non-users. Reduced EF was defined as EF ≤40%. The primary outcome was all-cause death. Subgroup analyses and meta-regression were conducted to explore heterogeneity. Meta-analysis was conducted using the restricted maximum likelihood method. Results There were 22 studies, including 1 RCT, involving 281,631 patients enrolled between 1997 and 2020. BB did not confer a significant reduction in all-cause death in patients with a 1-year event-free period (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%; Figure 1A), defined as no death, recurrent MI, or HF while on BB following index MI. In patients with a 3-year event-free period, a non-significant trend towards increased all-cause mortality was observed in BB users (HR, 1.39; 95% CI, 0.81 to 2.40; I2 = 0%; Figure 1A). For patients without a stable period, meta-regression showed BB morality benefits were modified by study inclusion period (P = 0.01; R2 = 51%; Figure 1B), indicating a temporal trend of decreasing mortality benefits of BB over time. Of note, BB exhibited no mortality benefits in patients enrolled after 2010 (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%; Figure 1C). Subgroup analysis showed BB led to a significantly lower all-cause death in patients with mildly-reduced EF (HR, 0.79; 95% CI, 0.68 to 0.91; I2 = 0%; Figure 2A). No mortality benefit of BB was observed in patients with preserved EF (HR, 0.83; 95% CI, 0.68 to 1.02; I2 = 66%; Figure 2A), however, with high statistical heterogeneity. Further exploration of this heterogeneity via meta-regression revealed a pronounced temporal trend of decreasing BB mortality benefits in patients with preserved EF (P <.0001; R2 = 100%; Figure 2B). The R2 value rising from 51% to 100% suggests that unexplained 49% heterogeneity is attributed to mildly-reduced EF patients. Similarly, BB's mortality benefit was not significant in patients enrolled after 2010 (HR, 1.02; 95% CI, 0.95 to 1.09; I2 = 0%; Figure 2C). Conclusion In the contemporary reperfusion era, BB do not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, given the temporal decreases in observed mortality benefits, especially in studies post-2010, BB may not remain an essential medication in post-MI care for patients with preserved EF in modern practice.Patients with/without a stable periodMildly-reduced and preserved EF patients