Beta-blocker therapy after myocardial infarction: an umbrella review

<h2>Summary</h2><h3>Background</h3> Beta-blocker therapy remains central to post-myocardial infarction (MI) management, but its benefit in patients with midrange or preserved left ventricular ejection fraction (LVEF) in the reperfusion era remains unclear. <h3>Methods</h3> We conducted an umbrella review and meta-analysis (PROSPERO CRD42024548877). Searches of MEDLINE, EMBASE, and Cochrane Library (January 2019–December 2025) identified systematic reviews and meta-analyses of adults (≥18 years) on beta-blockers for ≥1 year post–MI. Primary outcomes were all-cause mortality, cardiovascular mortality, and recurrent MI. Data from unique primary studies were pooled using random-effects meta-analyses stratified by study design: randomised controlled trials (RCTs), observational studies with propensity score matching (PSM), and non-PSM studies. Meta-regression assessed follow-up duration; subgroup analyses examined midrange (40–49%) and preserved (≥50%) LVEF. Sensitivity analyses were conducted to assess robustness, including the exclusion of studies with converted effect estimates, secondary validation analysis using aggregate estimates from included systematic reviews, and leave-one-out analyses. <h3>Findings</h3> Nineteen systematic reviews, encompassing 52 primary studies (n = 495,827), were included. Data from RCTs (7 studies, n=24,191), demonstrated a non-significant reduction in all-cause mortality (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.78–1.01) or cardiovascular mortality (HR 0.94, 95% CI 0.74–1.19). However, a significant risk reduction in recurrence of MI (HR 0.80, 95% CI 0.66–0.97) was observed. Observational studies generally reported larger protective associations for mortality, whereas PSM analysis showed concordant directionality with RCTs for recurrent MI, while non–PSM analysis yielded conflicting results. Meta-regression indicated that in RCTs, the benefit for cardiovascular mortality and recurrent MI attenuated with longer follow-up. In subgroup analyses, patients with preserved LVEF derived no significant mortality benefit from beta-blocker therapy in RCTs, while observational data suggested the greatest risk reductions occurred in those with midrange LVEF. Sensitivity analyses, including leave-one-out analyses, demonstrated stable effect estimates across outcomes, with no single study materially altering the direction of results. Validation analysis highlighted that larger effect sizes in prior meta-analyses were driven by observational data. <h3>Interpretation</h3> Contemporary evidence from RCT confirms that beta-blocker therapy does not significantly reduce mortality but is associated with a reduction in recurrent MI. This benefit appears to attenuate over time and is absent in patients with preserved systolic function. Collectively, these findings challenge the universal, long-term application of historical guideline recommendations and support an individualised, LVEF-stratified approach to beta-blocker therapy. <h3>Funding</h3> None.