Abstract
Introduction: Beta-blockers (BB) remain a cornerstone of secondary prevention after acute coronary syndrome (ACS). However, contemporary randomized trials have questioned their routine use in patients with preserved ejection fraction, often excluding those with atrial fibrillation (AF). We aimed to evaluate the prognostic impact of BB therapy after ACS and determine whether the presence of AF modifies its association with in-hospital and one-year mortality. Materials and Methods: We conducted a retrospective analysis of patients included in the Portuguese Registry of Acute Coronary Syndromes (ProACS), between October 2010 and 2021. Patients were stratified ac-cording to AF status and BB prescription. The two co-primary endpoints were in-hospital and one-year all-cause mortality. Results: A total of 14,906 patients were included (mean age 64 ± 13 years, 72.8% male), of whom 9.8% had AF. AF patients were older, had more comorbidities, and higher mortality (in-hospital: 8.6% vs. 1.8%; 1-year: 15.9% vs. 4.5%; p < 0.001 for both). BB therapy was associated with lower in-hospital mortality in both sinus rhythm (OR 0.19, 95% CI 0.14-0.24) and AF (OR 0.21, 95% CI 0.13-0.35), with consistent benefit after adjustment (adjusted OR 0.30, 95% CI 0.23-0.35). At one-year follow-up, BB therapy was associated with reduced mortality (HR 0.57, 95% CI 0.44-0.73), without significant interaction with heart rhythm (p-interaction = 0.335). Conclusions: AF is associated with worse prognosis after ACS. BB therapy is associated with reduced in-hospital and one-year mortality, with consistent benefit irrespective of heart rhythm. These findings suggest that AF does not modify the prognostic association of BB therapy after ACS.