Effect of beta blockers in acute and chronic coronary syndromes without reduced ejection fraction: a landmark analysis from the REBOOT trial

Abstract Background and Aims Current guidelines recommend beta-blocker therapy after myocardial infarction (MI) regardless of left ventricular ejection fraction (LVEF). However, recent trials question their benefit in patients with preserved LVEF. No study has yet compared beta-blocker effects during the acute coronary syndrome (ACS) phase (≤1 year post-MI) versus the chronic coronary syndrome (CCS) phase (1 year). Methods In this pre-specified landmark analysis of the REBOOT trial, we evaluated the effect of beta-blocker therapy on outcomes in two post-MI phases: the ACS period (first year; cohort 1, n = 8,438) and the CCS period (1 year, event-free patients with follow-up; cohort 2, n = 7,783). The primary endpoint was all-cause death, nonfatal reinfarction, or heart failure hospitalization; secondary endpoints included individual and additional cardiovascular events. Results Among 623 primary outcome events, 238 occurred in the first year (28.9/1,000 patient-years) and 385 thereafter (19.3/1,000 patient-years). Secondary prevention use was generally high, but patients with early events had lower prescription rates than those with late events or no events. Beta-blockers were not associated with lower risk of the primary or component outcomes in either phase. A nonsignificant trend toward benefit of beta-blockers appeared during the first year in patients with mildly reduced LVEF (41–49%), whereas in the CCS phase, higher beta-blocker doses were associated with worse outcomes. Conclusions In invasively treated MI patients with LVEF 40%, beta-blockers did not reduce adverse outcomes in either the ACS or CCS phases. These findings challenge their routine use in this population and support reconsidering current guidelines. Long-term beta-blocker users after MI may be candidates for deprescription.