Beta-blocker therapy after myocardial infarction: an umbrella review

Background Beta-blockers remain central to post-myocardial infarction (MI) management, but their benefit in patients with midrange or preserved left ventricular ejection fraction (LVEF) in the reperfusion era remains unclear. Purpose To synthesise evidence on the effectiveness, time-dependent effects, and role of LVEF in long-term beta-blocker use post-MI, stratified by study design. Methods We conducted an umbrella review and meta-analysis. MEDLINE, EMBASE, and Cochrane Library were searched (Jan 2019 - Dec 2025) for systematic reviews and meta-analyses of adults (≥18 years) receiving beta-blockers for ≥1-year post-MI. Outcomes were all-cause mortality, cardiovascular mortality, and recurrent MI. Beta-blocker use was compared with no use. Unique primary studies were pooled using random-effects meta-analyses stratified by study design: randomised controlled trials (RCTs), propensity score matched (PSM) observational studies, and non-PSM studies. Meta-regression assessed follow-up duration; subgroup analyses examined midrange (40–49%) and preserved (≥50%) LVEF. Sensitivity analyses excluded converted effect estimates and validated findings using aggregate estimates from included reviews. Results Nineteen systematic reviews encompassing 52 primary studies (n = 495,827) were included. In RCTs (7 studies; n=24,191), beta-blockers were not associated with all-cause mortality (HR 0.89, 95% CI 0.78–1.01) or cardiovascular mortality (HR 0.94, 95% CI 0.74–1.19) but reduced recurrent MI risk by 20% (HR 0.80, 95% CI 0.66–0.97). Observational studies showed mortality benefits but no significant effect on recurrent MI. In RCTs, cardiovascular mortality and recurrent MI benefits attenuated over longer follow-up; no time effect was observed for all-cause mortality. PSM studies showed no duration effect, while non-PSM studies demonstrated attenuation of mortality benefits over time. RCT subgroup analyses were limited to preserved LVEF, showing no outcome benefit; observational data suggested greater benefit in midrange LVEF for all outcomes. Sensitivity analyses confirmed robustness and indicated that prior larger pooled effects were driven by observational studies. Conclusions Contemporary RCT evidence indicates that long-term beta-blocker use post-MI does not reduce mortality but lowers recurrent MI risk, with effects diminishing over time and seemingly absent in preserved LVEF. Observational studies suggested potential benefits in midrange LVEF, though these findings are prone to confounding. High-level evidence questions universal long-term beta-blocker use and supports an individualised, LVEF-stratified approach.