Prognostic Impact of Carvedilol vs. Metoprolol on Long-Term Outcomes in Patients with Heart Failure and Mildly Reduced Ejection Fraction

Background: Evidence regarding potential agent-specific differences among β-blockers in heart failure with mildly reduced ejection fraction (HFmrEF) remains limited. Objective: The present study sought to investigate the association of metoprolol versus carvedilol prescribed at hospital discharge with 30-month all-cause mortality and HF-related rehospitalization, and to explore potential effect modification by atrial fibrillation (AF). Methods: Consecutive patients hospitalized with HFmrEF between 2016 and 2022 were included. Exposure was β-blocker therapy at discharge (metoprolol succinate or carvedilol). Outcomes were analyzed using Kaplan–Meier estimates, multivariable Cox regression and propensity score matching. Results: Among 2109 patients discharged alive, 1625 (77.5%) received β-blockers (metoprolol n = 1033; carvedilol n = 283). Carvedilol recipients were younger (median 72 vs. 76 years) and more frequently had prior heart failure (44.2% vs. 33.2%). Thirty-month mortality occurred in 25.5% of metoprolol-treated and 31.8% of carvedilol-treated patients (unadjusted hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61–0.98; p = 0.031). This association was observed in patients without AF, but not in those with AF. After multivariable adjustments, the association remained directionally similar (adjusted HR 0.76, 95% CI 0.58–1.00). In the matched cohort (n = 246 per group), metoprolol was still associated with lower mortality (HR 0.65, 95% CI 0.46–0.93; p = 0.017). By contrast, HF-related rehospitalization did not differ significantly between the two groups. Conclusions: In this observational HFmrEF cohort, treatment with metoprolol at index hospital discharge was associated with lower 30-month mortality compared with carvedilol. Given the observational study design in line with the higher burden of comorbidities in patients discharged on carvedilol, further prospective studies are needed to clarify the impact of different β-blocker types in heart failure patients.