Recent trials have questioned the clinical benefit of beta-blockers in post–myocardial infarction (MI) patients with preserved left ventricular ejection fraction (LVEF). However, differences in pathophysiology and risk profile between MI with and without ST-segment elevation (STEMI and NSTEMI) may influence the effect of beta-blockers.

In this prespecified subgroup analysis of the REBOOT trial, which randomized invasively managed MI patients with LVEF> 40% to beta-blockers or control, we evaluated differences in long-term effects of the intervention between STEMI (n=4296) and NSTEMI (n=4142). The primary endpoint was a composite of all-cause death, reinfarction, or heart failure hospitalization over a median follow-up of 3.7 years.

The primary endpoint and its components occurred more frequently in NSTEMI than in STEMI. A significant interaction between MI type and beta-blocker allocation was observed (P=.027). Among STEMI patients, beta-blockers were associated with a higher incidence of the primary endpoint (HR, 1.27; 95%CI, 1.00-1.62), whereas NSTEMI patients assigned to beta-blockers showed no effect (HR, 0.89; 95%CI, 0.72-1.10). Notably, NSTEMI patients with mildly reduced LVEF (40% to 50%) on beta-blockers experienced significantly fewer events than controls.

The absence of clear clinical benefit from beta-blockers in invasively managed MI patients with preserved LVEF was consistent across STEMI and NSTEMI. The observed interaction by infarct type is exploratory and should not be interpreted as definitive evidence of harm associated with beta-blocker therapy in patients with STEMI and preserved LVEF. NSTEMI patients with mildly reduced LVEF may benefit from beta-blockers, warranting further investigation. (ClinicalTrials.gov: NCT03596385)