To Örebro University

Background: Beta-blockers are recommended indefinitely for secondary prevention following myocardial infarction (MI) with reduced left ventricular ejection fraction (LVEF), but adherence to long-term beta-blockers decreases over time.

Purpose: We investigated the effects of varying lengths of continuous beta-blocker use on the 6-year risk of cardiovascular outcomes after MI with reduced LVEF.

Methods: We used observational data from Swedish national registers to emulate a pragmatic, randomized controlled trial of different durations of beta-blockers in eligible individuals who had an MI with LVEF <40% between September 2010 and February 2022. Five treatment strategies were compared: continuous oral metoprolol succinate or bisoprolol after MI for up to 6 months, 7 to 12 months, 13 to 18 months, 19 to 24 months, and more than 24 months. The primary outcome was a composite of all-cause death and recurrent non-fatal MI. All eligible participants were cloned to each treatment arm and censored when they no longer adhered to the treatment strategy in the specific arm to identify their follow-up time based on observed treatment duration and disease status. Inverse probability weighting adjusted for baseline and time-varying confounding and selection bias, incorporating demographics, clinical presentation, emergency and in-hospital care, comorbidities, biomarkers, and concomitant medications.

Results: There were 5,849 eligible individuals with a mean age of 67.8 years, of which 4,872 (83.3%) were originally from Sweden and 1,408 (24.1%) were female. In addition, 3,054 (52.2%) of the individuals included were married or had a partner at baseline, and 1931 (33.0%) underwent secondary or higher education. The 6-year risk of the composite outcome was 25.4% (95% CI: 23.3%, 27.3%) for treatment up to 6 months, 24.3% (22.6%, 25.9%) for 7 to 12 months, 24.3% (22.4%, 25.9%) for 13 to 18 months, 23.8% (22.1%, 25.3%) for 19 to 24 months, and 23.1% (21.6%, 24.6%) for treatment beyond 24 months. Compared to the group who took the treatment for no longer than six months, risk differences ranged from -1.1% (-2.8%, 0.6%) for a treatment duration of 7 to 12 months to -2.3% (-4.3%, -0.2%) for treatment duration beyond 24 months. Similar trends were observed for all-cause death and recurrent MI separately.

Conclusions: In individuals with MI and reduced LVEF, our target trial emulation supports continuous oral beta-blocker beyond two years to improve cardiovascular outcomes.