Long-term beta-blocker therapy after revascularised acute coronary syndrome (ACS) with preserved ejection fraction: a multi-centre retrospective cohort study

Background Clinical guidelines for beta-blocker use after ACS are largely based on evidence from the pre-reperfusion era. However, the evidence for the long-term clinical utility and safety profile of beta-blocker therapy remains unclear in patients with coronary revascularisation and preserved left ventricular ejection fraction (LVEF ≥40%). Purpose To evaluate the association between long-term beta-blocker therapy and clinical outcomes in patients with revascularised ACS and preserved LVEF (≥40%). Methods We conducted a retrospective cohort study using target trial emulation and data from a global federated research network (January 2013–December 2021). Adults aged ≥18 years who underwent coronary revascularisation for ACS and had preserved LVEF (≥40%) were included. Patients with beta-blocker use within one year before the index event or with predefined contraindications (including severe chronic obstructive pulmonary disease or asthma) were excluded. Long-term beta-blocker therapy was defined as initiation within 14 days after the index event and continued up to one year. Patients receiving long-term beta-blockers were compared with those not treated with beta-blockers. The primary outcome was all-cause mortality within three years. Secondary outcomes included recurrent revascularisation and incident heart failure within three years. Safety outcomes comprised bradycardia, hypotension, and atrioventricular block. Propensity score matching was performed to balance baseline covariates. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results A total of 5,471 patients were eligible in the study period. After propensity score matching analysis, 3,254 patients (mean age 62 ±12.5 years; 32.6% women) were analysed (1,627 per group). In the primary outcome, no significant differences were found in 3-year all-cause mortality between patients with and without long-term beta-blocker therapy (6.5% vs 5.3%; hazard ratio [HR] 1.09; 95% confidence interval [CI] 0.82–1.45; p=0.54). In secondary outcomes, patients receiving long-term beta-blocker therapy had higher risk of recurrent revascularisation (HR 1.82; 95% CI 1.66–1.99; p<0.0001) and risk of heart failure (HR 2.86; 95% CI 2.49–3.29; p<0.0001) compared to those without beta-blocker therapy. Patients with long-term beta-blocker therapy also experienced higher risks of adverse events, including bradycardia (HR 2.38; 95% CI 1.92–2.95; p<0.0001), hypotension (HR 3.06; 95% CI 2.39–3.91; p<0.0001), and AV block (HR 2.14; 95% CI 1.27–3.61; p<0.001) compared to those without beta-blocker therapy, which are considered beta-blocker-related pharmacological adverse effects. Conclusion In patients with revascularised ACS and preserved LVEF (≥40%), long-term beta-blocker therapy was not associated with reduced mortality and was linked to higher risks of recurrent revascularisation, heart failure, and adverse haemodynamic events.