Beta-blocker therapy after myocardial infarction: an umbrella review

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.

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.

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.

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.

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