Association of Beta-blocker Therapy with Outcomes after ST-segment Elevation Myocardial Infarction Stratified by GRACE Risk Score: A Nationwide Registry Analysis

Background Associations between beta-blocker use following ST-segment elevation myocardial infarction (STEMI) and clinical outcomes remain uncertain in the contemporary era of near-universal early revascularization and drug-eluting stent (DES) implantation, particularly for patients with preserved left ventricular function. We sought to determine whether associations between beta-blocker use at discharge and outcomes varied across Global Registry of Acute Coronary Events (GRACE) risk strata. Methods We performed a post-hoc analysis of 11,866 STEMI survivors from two prospective nationwide Korean registries who underwent successful percutaneous coronary intervention (PCI) with second-generation DES. Patients were categorized by beta-blocker prescription at discharge. The primary endpoint was all-cause mortality at one year; secondary outcomes included major adverse cardiac events (MACE). Propensity-score matching and inverse-probability treatment weighting were employed to mitigate confounding. Variation in associations was examined across the continuous GRACE risk spectrum, categorized into low-risk (GRACE <85), intermediate-risk (GRACE 85-179), and high-risk (GRACE ≥180) strata. Results Beta-blockers were prescribed to 83.8% of the cohort. After propensity matching, beta-blocker use was associated with lower one-year all-cause mortality (2.7% vs. 4.2%; hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.44-0.91) and MACE (6.0% vs. 8.3%; HR 0.71; 95% CI 0.55-0.92). These associations attenuated by three years. The GRACE 2.0 score exhibited robust discrimination for mortality (AUC = 0.79; 95% CI: 0.76-0.82). Continuous interaction analyses showed small model-estimated absolute risk differences in low-risk patients (GRACE <85), whereas the largest model-estimated absolute risk difference was observed in intermediate-risk individuals (GRACE 85-179). Conclusions Among STEMI survivors treated with contemporary PCI, associations between beta-blocker use at discharge and outcomes varied according to baseline GRACE risk. No statistically significant association was observed in low-risk individuals (GRACE <85), whereas the association with lower mortality was most evident in the intermediate-risk group (GRACE 85-179). These hypothesis-generating findings warrant evaluation in randomized trials before being used to guide treatment decisions.