Metoprolol versus bisoprolol in patients with acute myocardial infarction: a target trial emulation study

Background β-blockers are Class I recommendations for acute myocardial infarction (AMI). However, guidelines do not differentiate among β-blockers within this class. Previous comparative trials have primarily focused on heart failure patients or compared non-selective versus selective β-blockers, with limited attention to within-class differences. Whilst metoprolol and bisoprolol are commonly prescribed β-blockers in patients with AMI, their comparative effectiveness remains unclear due to the lack of head-to-head clinical trials. Purpose To compare the effectiveness of metoprolol versus bisoprolol on one-year clinical outcomes in patients with AMI. Methods We conducted a target trial emulation using real-world data from a large-scale integrated electronic health record system (2013-2022). Eligible patients were hospitalised for AMI and received either metoprolol or bisoprolol. We applied a new-user design and predefined exclusion criteria, including prior β-blocker use within 180 days before admission and contraindications to β-blockers. Patients were matched 1:1 using propensity score matching to simulate random assignment to metoprolol or bisoprolol. In the intention-to-treat analysis, patients were followed for one year or until death. Non-adherent patients were censored in the per-protocol analysis. The primary outcome was one-year all-cause mortality. Secondary outcomes included one-year cardiovascular mortality, recurrent myocardial infarction, and stroke. Results Among 61,899 eligible patients, 9,744 were matched (4,872 per group). During one-year follow-up, bisoprolol was associated with higher all-cause mortality versus metoprolol (hazard ratio [HR] 1.35; 95% confidence interval [CI] 1.14-1.61; P = 0.001), with consistent results in per-protocol analysis. Dose-stratified analysis revealed a dose-dependent pattern: in the >25% to 50% of target dose group, bisoprolol showed increased mortality risk (HR 1.64; 95% CI 1.15-2.36; P = 0.007), which further amplified in the >50% of target dose group (HR 4.11; 95% CI 2.00-8.44; P < 0.001). Bisoprolol was also associated with higher cardiovascular mortality (HR 1.31; 95% CI 1.05-1.63; P = 0.016). No significant differences were observed for recurrent myocardial infarction (HR 1.07; 95% CI 0.90-1.26; P = 0.454) or stroke (HR 1.04; 95% CI 0.84-1.29; P = 0.739). Conclusions In this target trial emulation of AMI patients, bisoprolol was associated with higher all-cause and cardiovascular mortality compared with metoprolol, with a dose-dependent relationship.